Disclosed is a process for the preparation of the following compounds:

Ibrutinib is an organic small molecule having IUPAC name 1-[(3R)-3-[4-amino-3-(4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl]prop-2-en-1-one. It is described in a number of published documents, including international patent application WO 2008/039218 (Example 1b), and is described as an irreversible inhibitor of Btk.
Btk plays an essential role in the B-cell signaling pathway linking cell surface B-cell receptor stimulation to downstream intracellular responses. Btk is a key regulator of B-cell development, activation, signaling, and survival (Kurosaki, Curr Op Imm, 2000, 276-281; Schaeffer and Schwartzberg, Curr Op Imm 2000, 282-288). In addition, Btk plays a role in a number of other hematopoetic cell signaling pathways, e.g. Toll like receptor (TLR) and cytokine receptor-mediated TNF-α production in macrophages, IgE receptor (FcepsilonRI) signaling in Mast cells, inhibition of Fas/APO-1 apoptotic signaling in B-lineage lymphoid cells, and collagen-stimulated platelet aggregation. See e.g., C. A. Jeffries, et al., (2003), Journal of Biological Chemistry 278:26258-26264; N. J. Horwood, et al., (2003), The Journal of Experimental Medicine 197:1603-1611; Iwaki et al. (2005), Journal of Biological Chemistry 280(48):40261-40270; Vassilev et al. (1999), Journal of Biological Chemistry 274(3):1646-1656, and Quek et al (1998), Current Biology 8(20):1137-1140.
Ibrutinib is therefore being studied in Phase II and III clinical trials for various hematological malignancies such as chronic lymphocytic leukemia, mantle cell lymphoma, diffuse large B-cell lymphoma and multiple myeloma.
There are various processes for preparing functionalised bicyclic heterocycles, for example as described in US patent document US 2011/0082137, which includes syntheses to fused bicycles from pyrazoles and substituted hydrazines.
Ibrutinib may be prepared in WO 2008/039218 (Example 1b) in accordance with the following scheme:

First, 4-amino-3-(4-phenoxyphenyl)-1H-pyrazole[3,4-d]pyrimidine may be prepared in accordance with procedures described in WO 2008/039218, for instance by converting 4-phenoxybenzoic acid to the corresponding acyl chloride (by using thionyl chloride), which latter product may be reacted with malononitrile to prepare 1,1-dicyano-2-hydroxy-2-(4-phenoxyphenyl)ethene. The methoxy moiety is then methylated using trimethylsilyldiazomethane, and that methylated product is the treated with hydrazine hydrate to provide 3-amino-4-cyano-5-(4-phenoxyphenyl)pyrazole, which is reacted with formamide to provide 4-amino-3-(4-phenoxyphenyl)-1H-pyrazole[3,4-d]pyrimidine, as illustrated in the following scheme:

Thereafter, the 4-amino-3-(4-phenoxyphenyl)-1H-pyrazole[3,4-d]pyrimidine may have the requisite piperidinyl moiety introduced at the 1H-position (i.e. on the —NH of the pyrazole moiety). As indicated in the above scheme, this is done by means of a Mitsunobu reaction—more specifically by converting the hydroxy moiety of the Boc-protected 3-hydroxypiperidine-1-carboxylate to a better leaving group, thereby allowing a substitution reaction with the —NH moiety of the pyrazole (with inversion). Hence, the chirality of the hydroxypiperidine is translated into the product, which is then converted to the single enantiomer ibrutinib by Boc-deprotection and acylation with acryl chloride.
This process has a number of disadvantages, such as those associated with cost, efficiency and environmental disadvantages. For instance the Mitsunobu step may be wasteful, costly and cumbersome. It is therefore desired to find a new process that overcomes these disadvantages.
There is now provided a process for the preparation of a compound of formula I,

or a derivative thereof, wherein
R1 represents a nitrogen protecting group;
R1a represents —CN, —C(O)OR1b or —C(O)N(R1c)(R1d);
R1b, R1c and R1d each independently represent C1-6 alkyl, aryl or heteroaryl;
R2a represents:                (i) phenyl substituted at the 4-position with halo or —O—R2b; or        (ii) hydrogen;
R2b represents hydrogen or phenyl;
which process comprises reaction of a compound of formula II,

or a derivative thereof, wherein
R1a and R2a are as defined above;
X1 represents a suitable leaving group,
with a compound of formula III,

or a derivative thereof, wherein R1 is as defined above,
which process is hereinafter referred to as a "process of the invention".
In the processes of the invention described herein, it is indicated that "derivatives" may be employed, which includes salts and solvates. Hence, for instance the compound of formula (III), i.e. the hydrazine, may be in the form of the free base or in the form of a salt (e.g. a di-hydrogen chloride salt, although the hydrazine may be in another salt form). Where appropriate, "derivative" may also encompass a relevant protecting group (which may be removed later in the synthesis scheme). It should also be noted that compounds mentioned herein may exhibit isomerism, e.g. tautomerism.
It is further indicated above that R1 is a nitrogen protecting group. Such groups include those that result in the formation of:                an amide (e.g. N-acetyl)        optionally substituted N-alkyl (e.g. N-allyl or optionally substituted N-benzyl)        N-sulfonyl (e.g. optionally substituted N-benzenesulfonyl)        a carbamate        a urea        trityl (triphenylmethyl), diphenylmethyl, or the like
Hence, R1 may, amongst other groups, represent:
—C(O)Rt1 (in which Rt1 preferably represents C1-6 alkyl or optionally substituted aryl);
C1-6 alkyl, which alkyl group is optionally substituted by one or more substituents selected from optionally substituted aryl (e.g. preferably forming a benzyl moiety);
—S(O)2Rt2 (in which Rt2 preferably represents optionally substituted aryl); or, preferably, —C(O)ORt3 (in which Rt3 preferably represents optionally substituted aryl or, more preferably, optionally substituted C1-6 (e.g. C1-4 alkyl, e.g. tert-butyl (so forming, for example, a tert-butoxycarbonyl protecting group, i.e. when taken together with the amino moiety, a tert-butylcarbamate group) or a —CH2phenyl group (so forming a carboxybenzyl protecting group);
—C(O)N(Rt4)Rt5 (in which, preferably, Rt4 and Rt5 independently represent hydrogen, C1-6 alkyl, optionally substituted aryl or —C(O) Rt6, and Rt6 represents C1-6 alkyl or optionally substituted aryl).
Unless otherwise specified, alkyl groups as defined herein may be straight-chain or, when there is a sufficient number (i.e. a minimum of three) of carbon atoms be branched-chain, and/or cyclic. Further, when there is a sufficient number (i.e. a minimum of four) of carbon atoms, such alkyl groups may also be part cyclic/acyclic. Such alkyl groups may also be saturated or, when there is a sufficient number (i.e. a minimum of two) of carbon atoms, be unsaturated.
The term "aryl", when used herein, includes C6-10 groups. Such groups may be monocyclic, bicyclic or tricyclic and, when polycyclic, be either wholly or partly aromatic. C6-10 aryl groups that may be mentioned include phenyl, naphthyl, and the like. For the avoidance of doubt, the point of attachment of substituents on aryl groups may be via any carbon atom of the ring system.
The term "heteroaryl", when used herein, includes 5- to 14-membered heteroaryl groups containing one or more heteroatoms selected from oxygen, nitrogen and/or sulfur. Such heteroaryl group may comprise one, two or three rings, of which at least one is aromatic. Preferably, such groups are 5- to 12-membered, e.g. 5- to 10-membered.
Where mentioned herein, C1-6 alkyl, aryl and heteroaryl may be optionally substituted. Such substitution is possible if it does not affect the concept of the invention, i.e. the process(es) defined herein (which may be performed on certain compounds irrespective of the substitution pattern thereon). Such substituents include aryl (e.g. phenyl, itself optionally substituted by substituents selected from halo, alkyl and the like), alkyl, halo, —CN and the like.
It is indicated that X1 represents a suitable leaving group, and in particular may represent chloro, bromo, iodo, —OR3a (in which R3a represents optionally substituted alkyl, e.g. in which the optional substituent(s) include aryl such as phenyl, so forming e.g. —OCH3, —OCH2-phenyl or the like) or a sulfonate group (e.g. —O—S(O)2R4a, in which R4a represents optionally substituted alkyl or aryl, so forming e.g. —OS(O)2CF3, —OS(O)2CH3 or —S(O)2PhMe or the like, i.e. tosyl, mesyl or the like).
Preferred compounds of formula (I) that may be prepared by a process of the invention described herein include those in which:
R1a represents —CN;
R2a represents phenyl substituted at the 4-position by —O—R2b; and/or
R2b represents phenyl;
hence the compound of formula (I) is preferably:

the compound of formula (II) is preferably:

wherein, preferably, X1 represents —OR3a, in which R3a is preferably alkyl, more preferably unsubstituted alkyl and, most preferably, methyl, so forming a —OCH3 group;
and hence, most preferably, the compound of formula (II) represents:

For the avoidance of doubt, the compound of formula (III) is a single enantiomer containing a chiral centre that has an (R)-configuration. By single enantiomer, we mean that the compound is present in some enantiomeric excess (in this case, that there is more (R)-enantiomer present than the (S)-enantiomer), for instance in greater than 50% ee, e.g. greater than 60% ee. The chirality is retained in the process of the reaction, i.e. the reaction is stereospecific, and the compound of formula (I) thereby produced is also a single enantiomer with the same configuration at the relevant chiral centre. Downstream synthetic steps will also proceed with retention of the stereochemistry (unless specified otherwise).
Particularly preferred protecting groups that R1 may represent include those forming carbamates (especially the tert-butoxycarbonyl or t-Boc group and the carboxybenzyl or Cbz group) and substituted alkyl moieties (especially the benzyl group). Such protecting groups may be more easily introduced onto the compound of formula (III) and/or ultimately more easily removed from the relevant nitrogen atom in a downstream step.
Such a process of the invention may be conducted using the free base of a compound of formula (III) or salt thereof, e.g. a di-hydrogen chloride salt of the compound of formula (III). Further the protecting group R1 is preferably a non acid-labile protecting group (e.g. a group labile to base or removable though hydrogenation or the like) such as a carboxybenzyl (Cbz) protecting group. However, the choice of this protecting group is influenced by the choice of the protecting group R2 (e.g. the two are preferably mutually compatible) as indicated hereinafter.
In this aspect of the process of the invention, the compound of formula (III) (or derivative thereof, e.g. di-HCl salt) may be added to the compounds of formula (II). Preferably less than two equivalents of the compound of formula (III) is employed compared to the compound of formula (II), more preferably less than 1.5 equivalents. However, the equivalents ratio of compound of formula (III) to compound of formula (II) may be between 1.5:1 to 1:1.5, preferably between 1.2:1 to 1:1.2 and in particular, the ratio is about 1:1.
Preferably, this aspect of the process of the invention may be performed in a suitable solvent, such as in the presence of a polar solvent, such as an alcoholic solvent (e.g. ethanol) and/or water, or mixtures thereof. It is preferred that a mixture of an alcohol (e.g. ethanol) and water is employed. Compared to the weight of the compound of formula (II) employed, at least one (e.g. at least five, but preferably less than 20) volume equivalent(s) of the solvent/alcohol and at least one (e.g. at least five, but preferably less than 20) volume equivalents of water are employed. Preferably about 13 volume equivalents of the alcohol and about 10 volume equivalents of water are employed.
Preferably, the compound of formula (II) in the presence of a suitable solvent (as described above) is cooled to below room temperature, for example to below 10° C., e.g. to about 5° C. The compound of formula (III) (or derivative thereof) is then added to the mixture of compound of formula (II) and solvent. Preferably this is done so as to maintain the temperature of the reaction mixture below room temperature (e.g. at below about 10° C., preferably between 5 and 10° C.). For instance, this addition may be drop-wise.
This process aspect of the invention is preferably conducted in the presence of a base, such as an organic base, preferably an amine base such as a tertiary amine base (e.g. triethylamine). Preferably between one and four molar equivalents of base are employed in the process of the invention (compared to the molar equivalents of the compound of formula (II) or (III)), and more preferably between 1.5 and 2.5 equivalents are employed (e.g. about two equivalents). Preferably the base is added dropwise, and preferably the temperature is maintained at below room temperature (e.g. at below about 10° C., preferably between 5 and 10° C.).
After the addition of the base, the reaction mixture is the preferably allowed to warm to about room temperature, after which it is allowed to stir at that temperature for a period of time (during which the conversion to desired product compound (I) may be monitored), which may depend on the conversion rate to product. Typically, the reaction mixture is allowed to stir for at least 20 minutes, for example for about one hour, after which further water may be added (e.g. between about 10 and 20 volume equivalents), the reaction mixture may be cooled (again) to below room temperature (e.g. to below about 10° C., preferably about 5° C. or below, e.g. about 0° C.). The desired product may then solidify, and may therefore be separated/isolated by filtration. It may be further purified if required.
Such an aspect of the process of the invention has several advantages. For instance, the fact that the substituted hydrazine of formula (III) (that may be employed in e.g. the free base form, or in the salt form which may be formed in situ) is employed in the reaction has at least the following advantages:                (i) the use of hydrazine hydrate is avoided, which is a hazardous reagent to handle, especially at high temperatures (for instance hydrazine is combustible even in the absence of oxygen);        (ii) the reaction leads to a 1N-substituted pyrazole and hence downstream substitution at the 1N-position is circumvented (when substitution is required at that position), for instance a downstream Mitsunobu reaction to introduce a substituent is circumvented, the latter reaction generating enormous amounts of waste (e.g. the Mitsunobu reaction may require two equivalents of the 3-hydroxy-N-Boc piperidine, due to a competing elimination reaction);        (iii) the use of the expensive chiral 3-hydroxy-N-Boc piperidine is circumvented;        (iv) the reaction of compound (II) with a non-symmetrical hydrazine may be expected to result in a variety of products (as opposed to reaction with the symmetrical hydrazine itself) but however, advantageously and unexpectedly, the reaction proceeds in a regioselective manner. That is the process of the invention predominantly results in the formation of a pyrazole with a substitution pattern as depicted by the compound of formula (I), i.e. in the 1(N)-position the piperidine, R2a group (e.g. 4-phenoxy-phenyl) in the 3-position, etc, as opposed to a pyrazole with the piperidine at the 2-position adjacent the R2a group. Advantageously, the desired regioisomer is present in higher quantity than the undesired regioisomer, and for instance is present in a ratio of greater than 75:25 compared to the undesired regioisomer, more particularly, this ratio is greater than 90:10, and most advantageously there may be a negligible or undetectable amount of the undesired regioisomer.
Hence, this aspect of the process of the invention may be advantageous in terms of economy (e.g. cost of goods), efficiency and environmental considerations (e.g. less waste).
After the first process of the invention, the compound of formula (I) that is prepared may be converted to a compound of formula (IV),

or a derivative (including isomer) thereof, wherein R1 is as hereinbefore defined.
In the conversion to the compound of formula (IV), the compound of formula (I) may first be converted to a compound of formula (IVA),

or a derivative (including isomer), wherein X2 represent —OH or —NH2, and R1 and R2a are as hereinbefore defined.
For instance, for compounds of formula (I) in which R1a represents —CN, a corresponding product of formula (IVA) in which X2 represents —NH2 may be produced by reaction with either:                (i) formamide (HCONH2);        (ii) formamidine or a formamidine salt H—C(═NH)—NH3+X−, wherein X− represents a suitable counterion, such as a halide (e.g. Cl−) or an oxy anion (e.g. acyl-O−), so forming for example formamidine HCl or formamidine acetate or the like;        (iii) alkyl (e.g. ethyl) formimidate, or a salt thereof, such as ethyl formimidate HCl;        (iv) ethylorthoformate followed by ammonium acetate.
For compounds of formula (I) in which R1a represents —C(O)OR1b or —C(O)N(R1c)(R1d), a corresponding product of formula (IVA) in which X2 represents —OH (or a tautomer thereof, as depicted by formula (IVB) below) may be produced by reaction with for example, CH(OEt)3 optionally in the presence of a catalyst (e.g. ZnCl2, 0.1 equiv), followed by the addition of e.g. NH4OAc, which reaction may be performed in the presence of a suitable solvent (e.g. an aromatic solvent such as toluene):

Thereafter, compounds of formula (IVA) in which X2 represents —OH (or the tautomer, i.e. compound (IVB) depicted above) may be converted to corresponding compounds of formula (IVA) in which X2 represents —NH2, by first converting to the corresponding chlorinated derivative (which need not be isolated) followed by a nucelophilic aromatic substitution to provide the desired compound, conditions including the use of POCl3 (or another suitable chlorinating reagent) followed by reaction with NH4OAc (or another suitable source of ammonia).
For compounds of formula (IVA) in which R2a represents hydrogen, such a compound may be converted to a compound of formula (IVC):

wherein X2 is as hereinbefore defined, and X3 is a suitable group such as halo (e.g. bromo, chloro or preferably, iodo), which reaction may take place in the presence of a source of halide, for instance an electrophile that provides a source of iodine includes iodine, diiodoethane, or preferably, N-iodosuccinimide, and sources of bromide and chloride include N-bromosuccinimide and N-chlorosuccinimide, and which reaction may be performed in the presence of a suitable solvent such as an alcohol (e.g. methanol) or preferably a halogenated solvent (e.g. chloroform) or a polar aprotic solvent (such as DMF).
Compounds of formula (IVC), in particular those in which X2 represents —NH2, may be converted to compounds of formula (IVA) in which R2a represents phenyl substituted at the 4-position with halo or —OR2b, by reaction of the compound of formula (IVC) with a compound of formula (IVD):X4—R2aa  (IVD)
wherein R2aa represents phenyl substituted at the 4-position with halo or —OR2b (with R2b as hereinbefore defined), and wherein X4 represents a suitable group such as —B(OH)2, —B(ORw)2 or —Sn(Rw)3, in which each Rw independently represents a C1-6 alkyl group, or, in the case of —B(ORw)2, the respective Rw groups may be linked together to form a 4- to 6-membered cyclic group (such as a 4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl group, thereby forming e.g. a pinacolato boronate group), and wherein the coupling reaction may be performed in the presence of a suitable catalyst system, e.g. a metal (or a salt or complex thereof) such as Pd, CuI, Pd/C, Pd(OAc)2, Pd(Ph3P)2Cl2, Pd(Ph3P)4, Pd2(dba)3 and/or NiCl2 (preferred catalysts include palladium) and a ligand such as PdCl2(dppf).DCM, t-Bu3P or the like, optionally in the presence of a suitable base (e.g. a carbonate base, hydroxide base, etc) and a suitable solvent.
Where, e.g. for compounds of formula (IVA) as defined above in which X2 represents —NH2 (or a protected derivative thereof) and R2a represents phenyl substituted at the 4-positon by halo or —OH, then conversion to the compound of formula (IV) may be possible by a coupling reaction with X4-phenyl-O-phenyl or X4-phenyl, for instance using similar catalytic coupling reactions to those mentioned above.
Hence, ultimately compounds of formula (IV) may be prepared according to the processes mentioned above.
The processes discussed above (including those to prepare compounds of formula (IV) and (IVA)) are also embraced by the concept of the invention, and are also processes that may be referred to herein as a "process of the invention".
There is therefore provided a process for the preparation of a compound of formula (IV) which process comprises a process for the preparation of a compound of formula (I) as hereinbefore defined followed by a process for the conversion of (I) to (IV) as hereinbefore described.
There is also provided a process for the preparation of a compound (IV) or (IVA), which process comprises reaction of a compound of formula (I) (as hereinbefore defined) with a formamidine salt defined at (ii) above. Such a process is also an aspect of the invention and has associated advantages compared with reaction with formamide. For instance, the use of the formamidine salt may be advantageous as it circumvents the use of formamide, the latter being using in prior processes at high temperatures (e.g. at about 165° C., which represents a thermal hazard), whereas the use of the formamidine salt allows lower temperatures to be employed.
This aspect of the invention (conversion of compound (I) to compound (IV) or (IVA)) is preferably performed by reaction of the compound (I) with a formamidine salt (as defined hereinbefore). The formamidine salt is preferably an acetate salt and is preferably employed in excess compared with the molar equivalents of compound of formula (I) employed (e.g. in greater than two equivalents compared to compound of formula (I), e.g. greater than five equivalents, such as greater than 10 equivalents and preferably about fifteen equivalents).
This aspect of the process of the invention may be performed in the presence of a suitable solvent, which may be selected from aromatic solvents (e.g. toluene), alcohols, ethers and N-methyl-2-pyrrolidone, or the like. Glycols ethers may be particularly preferred (e.g. due to high boiling points), and a particularly preferred solvent is therefore ethylene glycol monoethyl ether. The solvent is preferably de-gassed and the reaction is preferably carried out under an inert atmosphere. More than five volume equivalents of solvent is employed (e.g. more than ten, and preferably around 13).
The resultant reaction mixture is then preferably heated to above room temperature, e.g. to above 40° C., e.g. above 60° C. such as above 80° C. Most preferably it is heated to above 100° C. However, the temperature of the reaction mixture is preferably below 160° C., for instance the preferred temperature range is between 100° C. and 140° C., most preferably between about 110° C. and 130° C. (e.g. about 120° C.).
The reaction mixture may be monitored for progress, consequently affecting the time period of the reaction. After adequate completion of the reaction, mixture may be allowed to cool down and the reaction mixture worked up to provided the desired compound.
There is further provided a process for the preparation of a compound of formula (III) as hereinbefore defined, which process comprises resolution of a corresponding racemic mixture (or derivative, e.g. protected derivative, thereof), which may be performed by means of chiral chromatography (e.g. using chiral SFC), thereby advantageously obtaining a compound of formula (III) in greater than 50% ee, for example greater than 60% ee. Given that the process of the invention is stereoselective, it is possible to purify downstream so as to provide an enantiomerically pure downstream compound.
Advantageously, this may produce product (compound (III)) in greater than 50% ee, for instance greater than 60% ee. Introducing the chirality at this stage allows the processes hereinbefore described to be effected, thereby circumventing other methods for introducing the chirality (e.g. using chiral 3-hydroxy-piperidine) and circumventing the undesired Mitsunobu reaction prior disclosed in a process for preparing ibrutinib.
Compounds of formula (III), or protected derivatives thereof may be prepared by reaction of a compound of formula (VI),

or a derivative thereof, wherein R1 is as hereinbefore defined, with a compound of formula (VII),R2—N(H)—NH2  (VII)
wherein R2 is hydrogen or a suitable nitrogen protecting group (which may be subsequently removed),
which may also be referred to as an aspect of the invention. This aspect of the invention may be conducted under standard dehydration reaction conditions optionally in the presence of a suitable solvent.
In general, the protection and deprotection of functional groups may take place before or after any of the reaction steps described hereinbefore.
Protecting groups may be removed in accordance with techniques which are well known to those skilled in the art and as described hereinafter.
The use of protecting groups is described in "Protective Groups in Organic Chemistry", edited by J. W. F. McOmie, Plenum Press (1973), and "Protective Groups in Organic Synthesis", 3rd edition, T. W. Greene & P. G. M. Wutz, Wiley-Interscience (1999).
The following scheme (which may have its individual numbering, as may the experimental section) provides a non-limiting example of various processes of the invention:

For instance, for compounds of formula (II) in which X1 represents an alkoxy leaving group —OR3a (or sulfonate), then such a compound may be prepared by alkylation (e.g. methylation) (or appropriate sulfonylation) of a compound corresponding to a compound of formula (II) but in which —OR3a represents —OH. Conversion of the —OH to other suitable leaving groups (e.g. to halo) may also be effected.
Compounds corresponding to formula (II) but in which —OR3a represents —OH may be prepared by reaction of a compound of formula (VIII),R2a—C(O)X1a  (VIII)
wherein X1a represents a suitable leaving group (e.g. chloro) and R2a is as hereinbefore defined, with a compound of formula (IX),NC—CH2—R1a  (IX)
wherein R1a is as hereinbefore defined, under suitable reaction conditions.
Some compounds described herein may be novel themselves, and hence in a further aspect of the invention, there is provided:                a compound of formula (I) or a derivative thereof        a compound of formula (III) or a derivative thereof, for instance in at least greater than 50% ee        a compound of formula (II), (IV) or (IVA) or a derivative thereof.
In an embodiment of the invention, there is provided a process for the preparation of ibrutinib:

which process comprises a process as defined herein, followed by conversion to ibrutinib, for example:                a process for the preparation of a compound of formula (I) as herein described, followed by conversion to ibrutinib        a process for the preparation of a compound of formula (IV) or (IVA) as herein described, followed by conversion to ibrutinib, for example by deprotection (i.e. removal of the R1 group) followed by acylation with acryl chloride        a process for the preparation of a compound of formula (III) as hereinbefore described, followed by conversion to ibrutinib, for example in accordance with the procedures described herein
Hence, there is also provided the use of certain compounds (e.g. the use of a compound of formula (I), (IV), (IVA) and/or (III)) as intermediates in the preparation of ibrutinib.
There is then further provided a process for the preparation of a pharmaceutical formulation comprising ibrutinib, which process comprises bringing into association ibrutinib (or a pharmaceutically acceptable salt thereof), which is prepared in accordance with the processes described hereinbefore, with (a) pharmaceutically acceptable excipient(s), adjuvant(s), diluents(s) and/or carrier(s).
In general, the processes described herein, may have the advantage that the compounds prepared may be produced in a manner that utilises fewer reagents and/or solvents, and/or requires fewer reaction steps (e.g. distinct/separate reaction steps) compared to processes disclosed in the prior art.
The process of the invention may also have the advantage that the compound(s) prepared is/are produced in higher yield, in higher purity, in higher selectivity (e.g. higher regioselectivity), in less time, in a more convenient (i.e. easy to handle) form, from more convenient (i.e. easy to handle) precursors, at a lower cost and/or with less usage and/or wastage of materials (including reagents and solvents) compared to the procedures disclosed in the prior art. Furthermore, there may be several environmental benefits of the process of the invention.

Processes and intermediates for preparing a medicament

Abstract: where R1, R1a and R2a have the definitions in the description, as well as a process to prepare other intermediates that may be useful to synthesize downstream products, especially compounds that are useful as medicaments, for instance Bruton's tyrosine kinase (Btk) inhibitors such as ibrutinib. Also disclosed are other processes, other intermediates and compounds per se.


The invention relates to a coating comprising a photochromic material, its production and its use. The photochromic material of the coating has an optically reversible photochromic effect, wherein the switching threshold is disposed outside of or in the boundary region of the visible range of the spectrum. According to the invention, the photochromic material is coated with an influencing material, so that the switching threshold of the coated photochromic material is shifted towards wavelengths longer than the switching threshold of the uncoated photochromic material.

The present invention relates to a coating comprising a photochromic material with an optically reversible photochromic effect, wherein the photochromic material has a switching threshold outside of or in the boundary region of the visible region of the spectrum, to a method of making a coating comprising a photochromic material with an optically reversible photochromic effect wherein the effect sets in at a certain wavelength, as well as to the use of such a coating.
According to the German textbook, "Rompp Chemisches Lexikon" (Chemical Encyclopedia), Volume 9, 1993 Georg Thieme Verlag, Stuttgart, N.Y., page 3403, a photochromic effect is described as the reversible property of a material, which is distinguished by a color change which takes place in the photochromic material when it is exposed to visible or ultraviolet light. However, some materials have a switching threshold for the onset of the photochromic effect which lies at the violet, high energy end of the visible region of the spectrum or at even shorter wavelengths, as a result of which the usability of such materials in the visible region of the spectrum is, at the very least, greatly limited.
It is an object of the present invention to increase the usability of photochromic materials in the optically visible spectral region of the electromagnetic spectrum.
This and other objects of the present invention are accomplished by a coating comprising a photochromic material coated with an influencing material such that the switching threshold of the coated photochromic material which forms a layer is shifted towards wavelengths longer than the switching threshold of the uncoated photochromic material.
The present invention further relates to a method wherein the photochromic material is acted upon by an influencing material.
By using an internal light effect, the switching threshold of the photochromic effect can be shifted to longer wavelengths and, thereby, to the optical region of the spectrum. As a result, less photon energy is required to utilize the photochromic effect. Since the sun has an intensity distribution within the visible region of the spectrum, in which the distribution maximum lies at a wavelength of about 500 nm, a large number of photons are available in daylight for the photochromic effect of the present inventive coating. This is expressed by a stronger absorption and, also a better coating color. Another advantage lies in the fact that, because of the shift in the switching threshold, a larger variety of lasers can now be used.
Other objects, advantages and novel features of the present invention will become apparent from the following detailed description of the invention when considered in conjunction with the accompanying drawings.

Coating comprising a photochromic material, a method for its production as well as its use


A data processing apparatus supporting simultaneous playback includes a processor, two tuners, a receiving element and a transmitting element. The first tuner generates first television data transmitted via a first frequency range, and provides the first television data to an internal playback device. The second tuner generates second television data transmitted via a second frequency range. The receiving element receives a data request for a selected television channel from an external electronic device. In response to the data request, the processor controls the second tuner to generate the second television data including video/audio data of the selected television channel. When the internal playback device performs playback according to the first television data, the transmitting element transmits the video/audio data of the selected television channel to the external electronic device for playback.

Field of the Invention
The invention relates in general to televisions, and more particularly to a technology capable of simultaneously playing multiple television channels.
Description of the Related Art
Various handheld mobile devices, such as mobile phones and tablet computers, have become extremely common in the recently years and are essential information receiving channels in the daily lives of many consumers. To enhance entertainment effects and sharing ability, some video/audio transmission standards have become available to allow handheld mobile devices to project screen images to display systems such as televisions or projects having larger display sizes. One focus among these transmission standards is Miracast™. Miracast™, using a wireless local area network (LAN) as a medium, enables an electronic device supporting such standard to share video images through wireless signals. According to this standard, apart from transmitting video images from a mobile device to a television system for display, a television system may also transmit television program images to a mobile device to display the television program images on a screen of the mobile device. Thus, a user is allowed to view television programs through the compact handheld mobile device.
FIG. 1 shows an exemplary functional block diagram of the above transmission architecture for illustrating signal correlation between a television system 100 and an electronic device 150. A tuner 110 receives external television signals. When a user wishes to view a certain television channel using a video/audio playback device 12, an associated instruction may be transmitted through a remote controller or an external key (not shown) of the television system 100. In response to the instruction, a processor 13 sets the tuner 11 to receive data of a frequency range associated with the television channel, prompts a signal processing unit 14 to retrieve video/audio data of the television channel from an output signal of the tuner 11, and performs processes of demodulation, decoding and image optimization on the retrieved video/audio data. A video/audio playback device 12 then receives and plays an output signal from the signal processing unit 14. A receiving element 15 and a transmitting element 16 operate according to the Miracast™ transmission standard. As shown in FIG. 1, a signal transmission line is provided between the signal processing unit 14 and the transmitting element 16. When the receiving element 15 receives a request for obtaining a television program image from the electronic device 150, the processor 130 controls the transmitting element 16 to transmit the output signal of the signal processing unit 14 to the electronic device 140.
The above architecture suffers from one drawback. That is, an image that the television system provides to the handheld mobile device is synchronous with an image that is being played by the television system. In other words, when the television system is playing a program of a certain television channel, a user using the handheld mobile device cannot opt to watch a program of another television channel.

Method and data processing apparatus supporting simultaneous playback


A cartridge for a valve housing having outlets, the cartridge comprising a stationary body sleeve for fixed insertion within the housing and having outlet ports permanently aligned with the outlets of the housing, a moveable substantially hollow stem sleeve inserted within the stationary body sleeve and having an opening selectively alignable with the ports of the stationary body sleeve, the body sleeve and hollow stem being connected to one another by a retaining ring which aligns and maintains the cartridge as a unit in the housing. The diverting valve may be installed as a deck mounted fixture in a tub, whirlpool, soaking bath, spa, roman tub, or the like wherein the tub spout is located below the flood line rim of the respective fixture wherein the diverting valve can be repaired by replacing the cartridge from the top of the valve by removing the handle and replacing the cartridge in its entirety.

Back flow preventers and check valves are used in commercial and household installations, for example, bidets, Roman tubs, barber shop and hairdressing salon fixtures, laboratory sinks, food processing facilities, chemical manufacturing, metal plating facilities and all types of plumbing applications where the potable water outlet when installed is below the flood level rim of the fixture, just to name a few, to prevent the contamination of the potable water supply. The water in each case is used in different manners and the installation of back flow preventers and check valves would be required for each use to protect the water supply from contamination or a separate back flow preventer and check valve would be installed in the line in advance of the components in the system. For example, in residential installations of a bidet, the water is diverted to the rim or the spray. In a soaking or whirlpool bath tub the water is diverted to the spout, shower head or removable hand-held shower. A number of proposals have been made for the diversion of fluids. Various methods and devices have been used to protect the potable water system from contamination. The premises may be isolated to protect the purveyor's water distribution system by installing a back flow preventer at the water line into the building. An area may be isolated when a portion of the building has toxic material used there. That portion of the building should be isolated by installing a back flow preventer so as to protect the individual consumer using the water within the building. Finally one may individually isolate each fixture or piece of equipment from the water system such as is the case in Applicant's own structure described in Canadian Patent 1,225,006 and U.S. Pat. No. 4,589,438 which provides atmospheric back flow prevention, in a compact, easily manufactured, effective unit. The present invention describes improvements thereto by adding a plurality of checking devices and improves the structure and repair of the diverting valve.
It is well known that any deck mounted faucet with removeable spout or where the water spout outlet is installed below the flood level rim of the fixture that installation is required by law to have a vacuum breaker with check valves. These codes are set out by the ASME, CAN/CSA, IAPMO and CABO/ANSI (ADA) codes. Any installation for which there is risk of contamination to the potable water system. Such installations must meet all codes by providing vacuum breakers and check valves. In doing so, however, there is a considerable amount of cost resulting from installation of individual vacuum breakers with separate checks and the necessary piping to and from all the components along with the labour costs and the continual maintenance costs of such individual components. It would therefore be advantageous to provide all of these features within a cartridge system heretofore unknown. It would be desirable to have deck mounted valves with an integral cartridge accessible from the top for repair without requiring dismantling the deck mounted installation. It would also be advantageous to repair such a cartridge which may malfunction by merely removing such cartridge from the top of the deck simply by removing the diverter valve handle.
It is therefore an object of this invention, to provide a diverter valve with, integral atmospheric type vacuum breaker and inlet and outlet check valves in an integral structure which is entirely reliable and easily serviced from the top.
It is therefore another object of this invention to provide a deck-mounted tub installation wherein the spout is an integral part of the overflow and is below the flood level rim of the fixture including a diverter valve which meets all of the code requirements set out above.
It is a further object of this invention to provide a multiple deck mounted tub installation system including a diverter valve with integral atmospheric-type vacuum breaker and inlet and outlet check valves which conform with all codes and is economical and practical to acquire and maintain.
Further and other objects of the invention will be realized by those skilled in the art from the following summary of the invention and detailed description of preferred embodiments thereof.

Diverter valves with integral back flow preventer and inlet check and outlet check valve mechanisms and improvements therefor


Composites, products made from composites and method of producing same are provided. The present invention includes an injection moldable product made from a composite material at least composed of balanced mixture of thermoplastics and fibrous components. The injection moldable product is formed into a body that has a wedge-shape, a shim-shape or the like wherein the body includes one or more cored regions extending though at least a portion thereof.

The present invention generally relates to composites and products made from composites. More specifically, the present invention relates to composite products with a tapered body, such as shims, wedges and/or the like, and methods of producing same.
In general, composites and products made from composites are known and used in the market place. For example, composite products have been known and used as substitutes for products made from wood. In this regard, wood composite products have been used, for example, as a substitute for outdoor decking material made from wood.
As a wood substitute, composite products may exhibit similar, if not better, consistency of properties, such as compression strength, water resistance, pest resistance, rot resistance and/or the like, as compared to wood. In this regard, composites are generally made from a combination of plastics and a wood material, such as wood flour derived from a variety of different wood sources. Depending on the particular use, the composites are typically formed into an extruded product of varying sizes and shapes.
Within the manufactured home industry, for example, there exists a need for low cost and consistent performance in shims, wedges and/or the like. Wood shims and/or wood wedges typically vary with respect to properties and dimensions resulting in increased labor costs during use. In general, shims are utilized to position and level doors, windows, cabinets, framing and the like prior to being secured in place. In general, wedges are used to set and/or level heavy weight bearing objects, such as manufactured homes. Pre-made shims or setting wedges can facilitate operation due to the fact that extra time and effort does not have to be expended, for example, in sorting through a random assortment of commercially available wood shims for one with the necessary dimensions and quality.
However, wood shims, pre-made or otherwise, can split when a nail or nails are driven through a door jamb, for example, and subsequently into the shim to secure the door. This may result in having to replace the split shim and thus ultimately having to re-position the jamb. Further, once the shim has been secured in place, a portion of it generally needs to be removed such that it remains flush with, for example, the door jamb. In this regard, wood shims may not break cleanly or evenly when a portion is removed and thus can leave a jagged edge which may need additional cutting. Wood wedges can be problematic as well due to the fact that they are susceptible to slippage and/or compression over time under weight bearing use. This can cause shifting of the weight bearing objects, such as shifting of manufactured homes, set on the wood wedges.
A need, therefore, exists to provide composite products, such as shims and/or wedges, that can be readily manufactured and that have improved qualities, such as durability with resistance to split, splinter, swell, warp and twist, as compared to, for example, wood-made products.

Composite products and methods of producing same


The present invention pertains to novel tapes, tools and seaming systems for creating seams of rolled goods, especially carpeting, using induction heating. The present invention also provides improved seaming tapes for use in resistive heating methods.

It is well known to attach rolled goods and other rigid and semi-rigid goods to an underlying surface or substrate through any number of traditional methods including mechanical fasteners such as nails, staples, screws, tacks and brads, and chemical fasteners such as adhesives and cements which cure by volatilization of solvents, heat or chemical reaction. Additionally, Remerowski et. al. (U.S. Pat. No. 5,935369) and Krzeszowski (U.S. Pat. No. 4,123,305) teach methods of bonding rolled goods to a work surface through induction bonding. However, in many applications, especially carpet seaming, it is undesirable to effect a bond between the rolled good and the underlying substrate or intermediate, in the case of a carpet and the intermediate carpet padding, while creating a seam bond between opposing edges of the rolled good or of adjacent pieces of a rolled good. While stitching of seams is common for most rolled goods applications involving fabrics and textiles, stitching is not always practical or possible, especially in applications where the presence of a visible seam would be unsightly as on a large tapestry, canvas or the like.
In order to address concerns relative to seaming of rolled goods without stitching, a number of different technologies and methods have been devised. For example, simple heat activated tapes comprised of a backing and a layer of a hot melt adhesive on one or both sides of the backing have been developed for butt end and overlap seaming, respectively, of generally thinner fabrics and textiles or overlap seaming of thicker fabrics and textiles. These tapes are activated in place by passing a traditional consumer iron over the site of the seam.
The heat of the iron passes through the fabric or textile to the adhesive, melting the same and forming a bond once the heat source is removed and the hot melt allowed to cool. However, care must be taken in forming the seam so as to avoid scorching the fabric or even melting of the fabric (especially in the case of certain fabrics of low temperature synthetic polymers and elastomeric materials) with the hot iron as well as leakage or squeeze-out of the adhesive from the edges of the tape. Furthermore, if adhesive leaks through the seam or bleeds through the rolled good itself and comes in contact with the hot iron, noxious fumes may arise and, more importantly, the iron may no longer be suitable for its traditional use of pressing or ironing articles of clothing and the like.
The problems associated with the use of adhesive tapes are compounded and magnified in the seaming, particularly butt end seaming, of heavy duty, thick fabrics as used for tapestries and curtains and especially in the seaming of carpets. For convenience, the following discussion will be directed to carpet seaming. Carpet seaming tapes are generally 3–6 inches in overall width and are comprised of a heat-activated adhesive coated in the central 2–5 inches of these tapes, preferably a hot melt adhesive, a reinforcing fabric, and a carrier paper, oftentimes coated with a silicone release coating on the backside. A general schematic of the traditional carpet seaming tape is shown in FIG. 1 where the tape 1 includes a paper backing 2, often creped and frequently coated with silicone release coating on the reverse side 4, a reinforcement strip or scrim 3 for strength and a thermally activatable adhesive 5. Reinforcement strip 3 can be a knit or woven material and may extend to the edge of the tape but is frequently ½ to 1 inch narrower than the paper carrier leaving equal spacing on each edge. The adhesive may be in the form of a layer or beads or a combination thereof, but, in any event, is placed a set distance from the edges of the tape to prevent the molten adhesive from flowing off the tape and inadvertently bonding the carpet to the pad during the heating and subsequent pressing steps. If this should occur, the silicone release coating on the underside of the tape ensures that the tape itself will not bond to the padding, although this will not prevent the back of the carpet adjacent to the tape from bonding to the pad.
This seaming method requires the operator to first place the seaming tape, adhesive side up, directly under the open seam defined by the opposing edges of the carpeting. Once the carpet and tape are properly aligned, the operator then lifts the carpet and inserts a specialized heating iron, whose lower surface is elevated to a sufficient temperature to activate or melt the adhesive, underneath the carpet and in direct contact with the heat activated adhesive of the seaming tape. Once the underlying adhesive has been melted or reacted, the hot iron is advanced along the seam to heat the next section of adhesive. Concurrently, the trailing edges of the carpet behind the iron are brought in contact with the molten adhesive, manipulated to mate opposing edges of the carpeting to match any designs that may be incorporated into the carpet, and then pressed into the molten adhesive to ensure good surface contact and integration of the molten adhesive into the rough surface of the carpet backing. Thereafter, the adhesive is allowed to cool to form the bonded seam. The desired outcome is a seam that is not distinguishable from the rest of the carpet when viewed from the top of the carpet after the carpet has been stretched onto a tack strip or like device that holds the finished carpet in place.
Though the foregoing is the most commonly practiced method of carpet seaming, it is not without its disadvantages. One particular disadvantage is the incidence of peaking of the carpet at the seam once the carpet is stretched. Numerous improvements to the carpet seaming tapes have been proposed for addressing this problem including the use of multiple tapes in a side-by-side relationship (Johnston et. al. U.S. Pat. No. 4,749,433), extra-wide tapes (Johnston et. al. U.S. Pat. No. 4,919,743), and plastic or metallic reinforcing elements (Matthews U.S. Pat. Nos. 5,691,051 and 6,110,565 and Matthews et. al. U.S. Pat. No. 5,198,300). Others have proposed the use of an excess of adhesive at the centerline of the tape. One way in which this has been achieved is through the use of specialized irons that include channels or channeling features on their lower surface which divert molten adhesive so as to create a ridge of excess adhesive directly under the seam. While all of these provide some relief to the peaking problem, they do so at the expense of added costs in relation to the materials and manufacturing of the tapes and/or tools.
While the modified irons would seem a most efficient means to ensure additional adhesive at the seam, they are not without problems and shortcomings. Most notably, if the adhesive is heated significantly above its melting point, its viscosity becomes so low that a substantial amount may flow away from the ridge region as the tool is advanced and before the applicator can properly align and place the carpet edges. Additionally, because the adhesive in the formed ridge area is exposed to the air for the longest period of time, cooling will result in some solidification or viscosity build up in the adhesive in this area so that even if the applicator can ensure that adhesive is present at the interface of the abutting edges, surface wetting may not be sufficient to ensure a strong bond at the interface, i.e., by the time the applicator is able to align and place the carpet edges in proper position and press the same into the adhesive, the adhesive may not be viscous enough to flow into the interface between the abutting edges and/or to develop a sufficiently strong bond with the consequence that when the carpet is stretched the abutting edges separate or open: much like a paper cut opens when one pulls the skin on opposite sides of the cut in opposite directions.
In addition to the foregoing problems, the hot iron method does not allow for ease of redoing a seam once formed. Should the applicator find the pattern is off or that a gap exists in the seam bond, he must employ extreme care in reopening the seam to the point of the problem. In this method, the only way to open the seam is to rip it apart and then strip the tape from the back of the carpet. This process can severely damage the carpet and the carpet backing. Similarly, this method and tool do not allow for simple repairs in the event one needs to replace a small section of carpeting, for example to repair a cigarette burn, or to re-bond a small segment of the seam that has opened due to traffic. In essence, one must open an area sufficiently large to enable the tool to be placed under the carpet and removed. Furthermore, the heat of the tool often causes a relaxation of the twist of the carpet pile resulting in a noticeable difference in the carpet texture at the seam.
Besides the aforementioned difficulties with the process, the hot iron method has a number of additional concerns as well, including health and safety related concerns. For example, the hot iron generates the emission of strong, offensive fumes from the adhesive. Additionally, because the irons, during use, generate a build up of adhesive and adhesive residue on the underside of the iron, i.e., that side in contact with the adhesive, the operator must often raise the temperature of the tool periodically during the seam forming operation in order to ensure good melting/activation of the adhesive. This can even occur during a single seam forming operation where it is not possible to interrupt a seaming operation to remove and clean a tool without seriously risking problems. As noted above, such higher temperatures result in lower viscosities of the adhesives, increasing the likelihood that adhesive will leak beyond the tape edges and bond the carpet and/or the tape to the underlying pad or flooring as well as through the tape backing itself. Additionally, such hot irons can permanently distort the carpet backing as well as the carpet structure itself as a result of scorching or, in the case of polymer based materials, melting and/or relaxation of the carpet fiber twist; cause severe burns in workers who accidentally touch or come in contact with the hot surface of the iron; cause the emission of noxious fumes as a result of the melting and scorching of the adhesive. Additionally, a build up of adhesive and adhesive residue on the iron interferes with the heat transfer from the iron to the adhesive, thus slowing down the overall seaming process and unduly extending the time needed to complete the job.
A number of alternative technologies have been developed in an effort to address some of the problems with the traditional irons and seaming techniques. In particular, concerns relative to adhesive buildup on the iron and the concomitant need for higher temperatures for the iron, and the associated problems with such higher temperatures, are eliminated by seaming methods and devices wherein the heat needed for activating or melting the adhesive is generated within the seaming tape itself and no tools come in direct contact with the adhesive. Additionally, these alternative methods involve tools that do not become excessively hot in use and, thus, concerns for burns to the applicator or the carpet are not an issue. Further these alternative technologies do not involve the use of tools which travel beneath the carpet and above the seam tape, thus making the seaming method much easier.
One of the alternative methods involves resistance heating as a means of melting or activating the adhesive. For example, Brooks (U.S. Pat. No. 4,416,713), Middleton (GB 1,499,801) and Rodenbaugh (GB 1,507,851) each teach methods of carpet seaming using electrically conductive seaming tapes, i.e., seaming tapes similar to those used in traditional iron seaming methods except that they have an electrically conductive resistance element incorporated into the tape. In practice, each end of the tape is connected to an electrical current supply source to create a circuit. Heat generated by resistance heating as the current passes through the conductive element then melts or activates the adhesive. This eliminates many of the problems with the hot iron method and device but creates additional problems as mentioned below.
Because the tape is activated for the whole length of the seam at once, special care must be taken to ensure that the whole seam is properly aligned before inducing the current. Any movement of the carpet before the seam is cured or set, even as a result of a misstep by the applicator at or near the seam, may throw the entire seam out of alignment. Additionally, any break in the conductive element in the tape will render the entire length of the conductive seaming tape ineffective. In this respect tears or breaks in the conductive material may occur during the manufacture of the tape, in the course of laying the tape and carpet or as a result of forces pressing down on the tape after its placement, e.g., as a result of a misstep or the placement of a heavy and/or sharp edged article on the seam. More importantly, this method requires costly, bulky and inconvenient current supply equipment capable of generating currents of over 100 amps in order to generate sufficient heat along a lengthy seam to sufficiently heat the adhesive.
To some extent the need for bulky and costly equipment may be addressed by superimposing one strip of the conductive material over another with an intervening electrically insulating material, isolating the one from the other, (Brooks U.S. Pat. No. 4,610,906) or by placing two narrow strips of conductive material in a spaced, side-by-side relationship along the length of the seaming tape (Baxter AU57288/80). In use, a conductive bridge is applied linking each conductive strip to the other at one end of the tape and the leads from the power source are attached to the conductive strips at the opposing end of the tape. Both tapes present problems of manufacture and handling to ensure that the conductive strips do not touch each other. In the latter, the strips must be placed carefully to ensure they do not touch; whereas in the former, care must be taken to ensure that nothing pierces the tape, a happenstance that could create a short through the electrically insulating layer. Furthermore, because the heat generated by the conductive material is fairly constant along the conductive element and across its width (assuming uniformity in the material), the use of thicker regions of adhesive can create problems as the time to melt the adhesive in such regions is longer than in thinner regions. Thus, the adhesive in the thinner regions will achieve a lower viscosity and have a greater tendency to flow before the adhesive in the thicker regions is sufficiently melted to effectively bond the carpet. This can lead to leakage of the adhesive from the seam.
A second alternative carpet seaming technology relies upon induction heating and induction activatable seaming tapes. Induction activatable seaming tapes are similar, in many respects, to the resistance tapes except that heating results from eddy currents and hysteresis effects that are induced in a susceptor material, e.g., a foil layer or strip, upon being exposed to electromagnetic fields. Although Middleton (GB 1,499,801) primarily focused on resistance tapes wherein the conductive medium is a perforated conductive foil, Middleton also indicates that these tapes may be activated by induction. Nakano (EP 0237657) also teaches carpet seaming using induction activatable adhesive tapes that are activatable upon exposure to alternating magnetic fields of high frequency. Finally, Sakai et. al. (JP 1200937 and JP1203825) teach induction heating apparatus and induction carpet bonding methods wherein the induction tool for generating the high frequency magnetic field has three circular coils in a linear relationship corresponding, in use, to the centerline of the seaming tape. It is believed that this technology was commercialized by Hiroshima in Japan; however, it has since been removed from the market due to poor performance and acceptance of the product.
While induction seaming methods as taught in the prior art will address many of the issues and detriments of the iron seaming method and the resistance seaming method, they still have various shortcoming of their own. For example, leakage of activated or melted adhesive from the edge of the tape is still of concern, especially if the adhesive as applied to the tape is close to the edge. More importantly, induction tools and induction activatable tapes taught to date for use in carpet seaming suffer from poor heating in the area of the seam line or centerline. With such tapes and tools, the prominent heating occurs at the edge of the susceptor and not at the centerline of the susceptor. Indeed, the traditional induction tools taught in the aforementioned art provide little, if any, heating at the centerline of the tape due to the fact that the induced electric field and heating is very weak directly under the center of the coil. Since the carpet seam itself overlies the centerline of the tape, that area of the seam that most needs heat to ensure a good bond receives the least amount of heat. Consequently, there can be un-bonded gaps or weaknesses in the seam as a result of incomplete or insufficient heating of the adhesive directly under the seam. Although activation of the induction tool for longer periods of time may allow additional heat to traverse the tape to the centerline, in reality this is not likely to occur to any significant extent since the more ready direction of heat transfer is through the foil to the other layers of the tape and carpet rather than across the thin foil. Consequently, even if such transverse heating were possible, by the time sufficient heat transferred to the centerline area, the other components of the tape and carpeting in contact with those regions of the tape where heating was effected, particularly at or near the edges of the susceptor, would suffer from excessive heating resulting in scorching and burning of the adhesive, other tape components and/or the carpeting. These problems are even further magnified and compounded if the tapes employed thicker adhesive regions in the centerline area.
Thus, there remains a need in the art to design heat activatable tapes that lessen or eliminate the concern for adhesive leakage or squeeze-out, without increasing, or substantially increasing, the costs of the tape.
There also remains a need in the art to design tapes which are readily activatable by induction and provide suitable, durable carpet seams and, in a preferred respect, have thick regions of adhesive in the centerline to enhance butt end bonding and reduce the likelihood of peaking without being concerned that excessive induction times and heat would be needed and without risking scorching or burning of the tape, the carpet backing or even the carpeting itself.
There also remains a need in the art to design induction seaming systems whereby induction tools and tapes are specifically designed for use in combination so as to provide enhanced performance, whether for addressing adhesive leakage or squeeze-out, peaking or merely for improving bonding in the centerline region of the tape without overheating the edges of the tape.

Induction seaming tapes, systems and methods


An illumination system includes a plurality of radiation generating sources, such as LED dies. A corresponding plurality of optical waveguides is also provided, with each waveguide having a first and a second end, with each first end being in optical communication with the corresponding LED die. An array of corresponding passive optical elements is interposed between the plurality of LED dies and the corresponding first ends of the plurality of optical waveguides. The illumination system provides for substantially high light coupling efficiency and an incoherent light output that can appear to the human observer as arising from a single point of light. In addition, the light can be output remotely at one or more locations and in one or more directions.

1. Field of the Invention
The present invention relates to a lighting or illumination assembly and system. More particularly, the present invention relates to a high coupling efficiency illumination system including a plurality of light sources.
2. Background Art
Illumination systems are used in a variety of applications. Home, medical, dental, and industrial applications often require light to be made available. Similarly, aircraft, marine, and automotive applications require high-intensity illumination beams.
Traditional lighting systems have used electrically powered filament or arc lamps, which sometimes include focusing lenses and/or reflective surfaces to direct the produced illumination into a beam. However, in certain applications, such as in swimming pool lighting, the final light output may be required to be placed in environments in which electrical contacts are undesirable. In other applications, such as automobile headlights, there exists a desire to move the light source from exposed, damage-prone positions to more secure locations. Additionally, in yet other applications, limitations in physical space, accessibility, or design considerations may require that the light source be placed in a location different from where the final illumination is required.
In response to some of these needs, illumination systems have been developed using optical waveguides to guide the light from a light source to a desired illumination point. One current approach is to use either a bright single light source or a cluster of light sources grouped closely together to form a single illumination source. The light emitted by such a source is directed with the aide of focusing optics into a single optical waveguide, such as a large core plastic optical fiber, that transmits the light to a location that is remote from the source/sources. In yet another approach, the single fiber may be replaced by a bundle of individual optical fibers.
The present methods are very inefficient with approximately 70% loss of the light generated in some cases. In multiple fiber systems, these losses may be due to the dark interstitial spaces between fibers in a bundle and the efficiencies of directing the light into the fiber bundle. In single fiber systems, a single fiber having a large enough diameter to capture the amount of light needed for bright lighting applications becomes too thick and loses the flexibility to be routed and bent in small radii.
Some light generating systems have used lasers as sources, to take advantage of their coherent light output and/or low divergence angle. However, laser sources typically produce a single wavelength output color whereas an illumination system typically requires a more broadband white light source. For example, U.S. Pat. No. 5,299,222 discusses the use of single wavelength high-power laser diodes to couple energy into a wavelength sensitive gain medium, as opposed to use as an illumination source. The use of the specified laser diodes, with their asymmetrical beam shape, requires the extensive use of optical beam shaping elements in order to achieve more efficient coupling into the optical fibers. Also, some laser diodes are expensive to utilize since they require stringent temperature control (e.g., the need for using thermoelectric coolers, and the like) due to the heat they generate in operation. In addition, a concentrated array of packaged LEDs can lead to problems in the area of thermal management.
The need remains for a lighting system that can deliver high-intensity illumination using a light source.

Illumination system using a plurality of light sources


A dispersion strengthened mechanically alloyed aluminium based alloy is provided which is prepared by mechanical alloying and is characterized by improved isotropic strength, fracture toughness and corrosion resistance. The alloy system contains by weight 1.2 to 1.6% lithium, 4.0 to 6.0% magnesium, 0.15 to 0.7% carbon, up to 1% oxygen and up to 2.0% in total of one or more grain controlling elements to provide microstructural optimization and control, the balance aluminium save for incidental impurities.

This invention relates to high strength isotropic dispersion strengthened aluminium-lithium alloys and in particular to those alloys suitable for fabrication, via an mechanically alloying route, into forged, extruded or rolled products made therefrom.
In recent years considerable research efforts have been expended to develop high strength aluminium to satisfy the demands of advanced design in aircraft, automotive and electrical industries. Aluminium-lithium alloys are of interest in these fields because the addition of lithium offers the possibility of improving properties of aluminium with respect to density and elastic modulus. The level of addition of lithium is chosen to avoid precipitation of the xcex4xe2x80x2 phase, Al3Li which would render the alloy heat treatable and so compromise its properties. Magnesium additions are also known to reduce the solubility of the lithium in the matrix and thus can render the alloy susceptible to age hardening. Magnesium has the further advantage of adding a component of solid solution strengthening. To meet the qualifications for certain advanced design applications, a combination of property requirements must be met including required density, strength, corrosion resistance, fracture toughness and ductility.
The use of a technique known as mechanical alloying to produce dispersioned strengthened powders has been well documented for example in UK Patent No. 1 265 432 and U.S. Pat. Nos. 3,591,362; 3,740,210 and 3,816,080. Mechanical alloying, as described in the aforesaid patents, is a method for producing uniform, finely dispersed, homogeneous metal powders by means of the fracturing and rewelding of a mixture of fine powders during high energy impact milling. Mechanically alloyed materials are characterised by a fine grain structure which is stabilised by uniformly distributed dispersoid particles such as carbides and/or oxides. For most uses, the powders produced by mechanical alloying are subsequently consolidated into bulk forms by, for example, degassing and then compacting the material. For fabrication into complex parts, this may be followed by extrusion, rolling or forging.
The problem with these techniques however, is that they are costly and time consuming; the handling and processing of a mechanically alloyed powder with conventional levels of carbon has associated health and safety problems; it can be difficult to balance the mechanical property requirements.
Aluminium-lithium-magnesium alloys manufactured by the abovementioned methods which have increased strength have been disclosed in EP 0 180 144. Heat treatable aluminium-lithium alloys which do not suffer from a reduction in strength as a result of the heat treatment process have been disclosed in EP 0 194 700. U.S. Pat. No. 4,600,556 discloses aluminium-lithium-magnesium alloys with improved strength and fracture toughness without an unacceptable loss in ductility. It has now been surprisingly found that high (4-6%) magnesium contents increase toughness and do not cause xcex4xe2x80x2 phase precipitation provided the lithium content is less than 1.6%.
It is an objective of the invention to provide aluminium alloys with reduced health and safety problems as well as improved mechanical properties particularly isotropic strength and fracture toughness. The ultimate product forms of these materials are often complex shapes and it is a further object of the invention to provide aluminium alloys which can be manufactured and shaped using cost effective techniques, whilst retaining their desirable properties.
This present invention is directed towards the provision of a dispersioned strengthened aluminium based alloy having a composition within the following ranges, all of the ranges being specified in weight percent, comprising 1.2 to 1.6% lithium, 4.0 to 6.0% magnesium, 0.15 to 0.7% carbon, up to 1% oxygen, up to 2.0 in total of one or more further grain controlling elements and the balance, save for incidental impurities, aluminium.
The principle alloying elements are lithium and magnesium with further optional additions of up to 2.0% of one or more of the elements selected from those established in the art as suitable for microstructural optimisation and control. Preferably these further grain controlling elements are selected from scandium, titanium, vanadium and niobium at up to 0.2%, nickel and chromium at up to 0.5% and preferably at up to 0.2%, hafnium at up to 0.6% and cerium at up to 0.5%.
The carbon and oxygen in the alloy is generally provided by a process control agent added during the mechanical alloying process. In this alloy, according to the invention, the carbon level is lower than normally used for mechanically alloyed powders; but is sufficient to allow the production of the mechanically alloyed powder and has a number of advantages. The carbon and carbides in the system generally decorate the grain boundaries in the manufactured product, which consequently reduces the fracture toughness of the material. By reducing the level of carbon in the system, the inventors have determined that the amount present at grain boundaries is similarly reduced, resulting in a reduced presence of stress raisers. Crack propagation is therefore more difficult and fracture toughness is increased. The handling and processing of high levels of carbon in mechanically alloyed powders has associated health and safety problems which are reduced when less than 1% carbon is added. Further advantages of milled powders produced with low levels of carbon in accordance with the invention is that they are more coarse and therefore easier to handle. Another advantage of having a low level of carbon is that the milling time of the powder can be reduced. This is important as the mechanically alloying stage is time consuming and expensive.
In a preferred embodiment of the invention, the aluminium alloy contains by weight percent: 1.2 to 1.4% lithium; 4.5 to 5.5% magnesium; 0.25 to 0.35% carbon up to 1% oxygen. These levels of alloying additions give a good balance of properties. The properties of lithium and magnesium are such that the effects of solid solution strengthening produced by the magnesium addition are not significantly reduced by the level of lithium addition.
Alloys according to the invention are also found to exhibit improved isotropic tensile performance, fracture toughness and corrosion resistance.
In one route to fabrication, the alloy can be mechanically alloyed and the resulting powder degassed and compacted into billets. A person skilled in the art will realise that there are a number of different methods that can be employed to produce billets, hot isostatic pressing (HIP) is an example.
Billets can be fabricated into the ultimate product forms by extrusion, rolling, forging or other known methods. If complex parts are to be manufactured with little waste, a preferred manufacturing route to use is forging. Forging allows complex parts to be manufactured with near net shape resulting in very little material wastage and post manufacture working of the product is kept to a minimum. Two important parameters in the forging stage are forging temperature and the amount and type of reduction the billet encounters.
The forging temperature is critical to the metallurgical structure of the alloy. If the forging temperature is too high, the grains in the alloy grow which reduces the strength of the final product thus, the advantages gained in producing a mechanically alloyed powder are reduced. A number of factors influence the temperature that the alloy reaches during forging, including the temperature of the die, the temperature of the billetxe2x80x94before entering the die, the speed of forging, the amount of reduction in forging and the thickness of the final part. These factors influence not only the mechanical property differences in different parts but also within a part.
A preferred embodiment of the invention is characterised in that the alloy is forged at a temperature within the range 250 to 450 xc2x0 C. In a more preferred embodiment, the alloy billet is forged within the range 300 to 400xc2x0 C.
The amount and type of reduction used in the forging stage affects both the temperature of the forging and the mechanical properties of the product. Shear stresses produced in the billet during forging cause the breakdown of oxide boundaries present on the powder particles of the mechanically alloyed material. By breaking down these oxide boundaries, the forging process disperses the oxides in the material so reducing the chance of large particles of oxides being present on the grain boundaries of the forged product. This in turn results in a product with improved mechanical properties. The amount and type of reduction used depends partly on the type of forging process used. In open die forging, a reduction ratio of greater than 8:1 is necessary to fully develop the ductility of the alloy. In die forging, where the work is more constrained, lower reduction ratios are sufficient.


A collectible structure of delicate frangible hollow construction having a circular or other shaped opening in its rear wall is provided with a relatively axially short protective sleeve of tough composition fitting within the opening and retained therein, e. g. by frictional engagement with the opening edges. An illuminating unit having a light source for illuminating the collectible structure from its interior is placed within the sleeve with the light source disposed within the structure interior beyond the inner end of the sleeve. Attached to the unit are resilient spring supporting means therefor, preferably in the form of plural resilient outwardly-directed fingers, in engagement with an interior surface of the sleeve so that the sleeve surface bears the force of the supporting means. Preferably, the sleeve has a short arcuate segment removed from its perimeter to permit the sleeve to be compressed to fit different sized openings.

There are many different kinds of ornamental or decorative articles that are currently manufactured and sold with the intent of collection by those to whom the particular article has some kind of sentimental, emotional, historical or nostalgic appeal. Such articles can be collected with a view to creating a charming even beautiful display within one's home. While some of these articles retain only an intrinsic ornamental value, others after the passage of time and especially where the specific article was issued in limited quantity and/or experiences an unexpected demand can undergo an increase in economic value which can become surprisingly large. Thus, there can be a strong financial incentive to protect such articles from breakage or damage in addition to the normal desire to preserve one's possessions and since it is difficult if not impossible to predict in advance which collectible is likely to increase in value over time, this incentive tends to apply generally.
A very popular type of collectible in recent years are miniature hollow structures fashioned to resemble, or even reproduce on a small scale, some structure often well known having an historical or nostalgic significance or otherwise having a sentimental appeal or, alternatively, as a fanciful creation from a designer's imagination. The variety of subjects qualifying for such treatment is virtually unlimited and include castles, churches, lighthouses, cottages, manor houses, taverns, early rowhouses, figures, scenic views, etc., both historical and imaginary. Most of these articles by their very nature include openings or perforations and sometimes areas of reduced thickness and to augment their ornamental or decorative attraction, are illuminated from within their interior so that light streams from the openings or creates a translucence in thin regions.
For such illumination, these miniature structures have a special opening, preferably circular, in a rear, and ordinarily unseen, wall and an illuminating unit, such as a low wattage light bulb and associated socket, is disposed in this opening with a light cord extending to a convenient electrical source. A reasonably secure mounting of the socket within the rear wall opening is obviously desirable. While this objective could surely be achieved in many ways, one popular solution is to attach to opposite sides of the socket, opposed stiffly resilient spring fingers (or "wings") of steel, plastic or the like extending angularly outwardly relative to the socket axis in generally V-shaped fashion away from the bulb end of the socket. The angle of inclination of the fingers relative to their length is sufficient that the transverse separation of the fingers at at least a short distance inwardly from their free ends exceeds the diameter, or some other dimension in case the opening is not circular. The spring fingers are preferably flat but could have other shapes, e. g. rod-like.
Thus, the free ends of the spring fingers are compressed together for insertion in the rear opening and when released are spring-biased by their resiliency outwardly against opposite side edges of that opening. With flat spring fingers and a circular opening as preferred, the planes of the fingers extend chordally of the opening on opposite sides thereof. To insure that the spring fingers are retained in their engaged position, and resist the socket-bulb assembly from becoming dislodged by the spring action of the fingers or otherwise, a positive engagement over and above friction alone between the fingers and opening edges is preferably provided. For example, on opposite sides of the respective spring fingers at a point along their length where their separation is greater than the rear opening dimension, there can be, and preferably are, small indentations, such as short shallow U-shaped notches or the like. When the illuminating assembly is inserted in the rear opening and the spring fingers released, these indentations receive or catch on edge portions of the rear structure wall opening and effectively prevent unintended axial displacement of the fingers from the opening edges until the fingers are again deliberately compressed.
This technique while effective for mounting the light-socket unit within the collectible, has an important drawback. As stated above, the hollow structures are of delicate construction with a wall thickness of only 1/8 in or so and the rear opening edges are quite susceptible to damage from their engagement by the notched spring fingers of the unit. The security of this engagement in anchoring the unit in place is primarily a function of spring finger resiliency; strong resiliency is thus desirable but increases the risk of damage and loss of value. The bulb-socket unit is typically occasionally removed and replaced from an item, as e. g. when a collection of the collectibles is re-arranged for a different visual effect or replaced with a different collection in a seasonal change. The "attack" of the spring fingers on the opening edges can therefore be progressive, chipping away the edges with an increasing possibility of causing a major crack in the structure and diminishing or even destroying its value.

Protective shield for illuminated hollow frangible collectibles


A communication event notification method, an apparatus, and system, which relate to the communications field and can flexibly present notification information according to a preset condition. The method includes learning, by a central device, of a communication event; determining, by the central device, an identifier of at least one bridge device according to parameter information of a candidate bridge device, where parameter information of the at least one bridge device meets a preset condition; and sending, by the central device according to the identifier of the at least one bridge device, notification information corresponding to the communication event to the at least one bridge device.

The development of communications technologies has made mobile phone communication an indispensable part of people's routine life, for instance, all information exchanges between one user and another can be implemented by means of mobile phone communication. Generally, in some indoor environments, because of being away from a mobile phone, or other like cases, a user often misses a communication event such as a call or a short message. Consequently, the user cannot exchange information with another user.
In the prior art, when a user's mobile phone receives a communication event, a function of notifying the user may be generally implemented by using two methods. In one aspect, a smart television may be used to notify the user of a communication event received by the user's mobile phone. Optionally, a connection between the smart television and the mobile phone may be implemented by using a wireless communications technology. When receiving a communication event, the mobile phone may send the communication event to the smart television by using the wireless communications technology, so that the smart television can present the communication event to the user to notify the user of the communication event received by the user's mobile phone. In the other aspect, a wearable device may be used to notify the user of a communication event received by the user's mobile phone. Optionally, a connection between the wearable device and the mobile phone may be implemented by using a Bluetooth technology. When receiving a communication event, the mobile phone may send the communication event to the wearable device by using the Bluetooth technology, so that the wearable device can present the communication event to the user to notify the user of the communication event received by the user's mobile phone.
However, in one aspect, if the smart television is used to notify the user of the communication event received by the user's mobile phone, due to a limitation of a position where the smart television is placed, the user cannot see a notification of the communication event when the user is not near the smart television; therefore, a function of notifying the user by the smart television is subject to a geographical restriction. In the other aspect, if the wearable device is used to notify the user of the communication event received by the user's mobile phone, due to a limited effective distance of the used Bluetooth technology, the user cannot receive the notification of the communication event when a distance between the user and the mobile phone is greater than an effective distance of Bluetooth transmission; therefore, a function of notifying the user by the wearable device is subject to a distance restriction.

Communication event notification method, apparatus, and system


An improved cathode material for nonaqueous electrolyte lithium electrochemical cell is described. The preferred active material is ε-phase silver vanadium oxide (Ag2V4O11) coated with a protective layer of a metal oxide, preferably γ-phase SVO (Ag1.2V3O1.8). The SVO core provides high capacity and rate capability while the protective coating reduces reactivity of the active particles with electrolyte to improve the long-term stability of the cathode.

1. Field of Invention
This invention relates to the conversion of chemical energy to electrical energy. In particular, the present invention relates to preparation of an improved cathode for lithium electrochemical cells. The cathode contains a first metal oxide or metal sulfide, preferably silver vanadium oxide (SVO) or copper silver vanadium oxide (CSVO), coated with a second metal oxide or metal sulfide different than the first. One preferred composition has a core of ε-phase SVO (Ag2V4O11) provided with a coating of γ-phase SVO (Ag1.2V3O1.8). The core ε-phase SVO provides the cell with relatively high capacity and rate capability while the γ-phase SVO protective coating improves long-term cathode stability by reducing particle reactivity with the electrolyte. Improved long-term stability translates into increased discharge life in a lithium electrochemical cell. A sol-gel process preferably performs the coating. An exemplary application is having the cell power an implantable cardiac defibrillator, where the cell may run under a light load for extended periods of time interrupted by high rate pulse
2. Prior Art
As is well known by those skilled in the art, an implantable cardiac defibrillator is a device that requires a power source for a generally medium rate, constant resistance load component provided by circuits performing such functions as, for example, the heart sensing and pacing functions. From time-to-time, the cardiac defibrillator may require a generally high rate, pulse discharge load component that occurs, for example, during charging of a capacitor in the defibrillator for the purpose of delivering an electrical shock to the heart to treat tachyarrhythmias, the irregular, rapid heartbeats that can be fatal if left uncorrected.
It is generally recognized that lithium cells containing silver vanadium oxide and, in particular, ε-phase silver vanadium oxide are preferred for powering cardiac defibrillators. U.S. Pat. Nos. 4,310,609 and 4,391,729, both to Liang et al., disclose the preparation of ε-phase SVO as a cathode material for use in a nonaqueous electrolyte electrochemical cell. These patents describe the preparation of silver vanadium oxide by a thermal decomposition reaction of silver nitrate with vanadium oxide (V2O5) at a maximum temperature of about 360° C. The Liang et al. patents are assigned to the assignee of the present invention and incorporated herein by reference.
The reason silver vanadium oxide is preferred for cardiac defibrillators is because of its relatively high rate capability. For example, U.S. Pat. No. 4,830,940 to Keister et al. discloses a primary cell containing silver vanadium oxide for delivering high current pulses with rapid recovery, high capacity and low self-discharge. The Keister et al. patent is assigned to the assignee of the present invention and incorporated herein by reference.

Silver vanadium oxide provided with a metal oxide coating