text:
|Publication number
|Publication type
|Application number
|Publication date
|Nov 12, 1991
|Filing date
|Jul 9, 1990
|Priority date
|Jun 24, 1987
|Fee status
|Publication number
|William J. Kruper, Jr.
|Original Assignee
|The Dow Chemical Company
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|Patent Citations (2), Non-Patent Citations (10), Referenced by (52), Classifications (35), Legal Events (5)
|External Links: USPTO, USPTO Assignment, Espacenet
This application is a continuation-in-part of our co-pending application Ser. No. 289,163, filed Dec. 22, 1988, abandoned; our co-pending application Ser. No. 65,739 filed June 24, 1987, U.S. Pat. No. 4,994,560, our co-pending application Ser. No. 211,496 filed June 24, 1988, abandoned, and of our co-pending application Ser. No. 370,956 filed June 21, 1989.
The present invention relates to a process for preparing mono-N-alkylated polyazamacrocycles.
T. A. Kaden, Top. Curr. Chem. 121, 157-75 (1984) has shown that simple alkylative techniques using electrophiles and polyazamacrocycles for the production of mono-N-functionalized polyazamacrocyles result in the formation of a mixture of mono, bis, and tris alkylated products which are difficult to separate and purify. To overcome this problem, large excesses of macrocycle, for example 5-10 equivalents relative to electrophile, have been employed by M. Studer et al., Helv. Chim. Acta. 69, 2081-86 (1986), by E. Kimura et al., J. Chem. Soc. Chem. Commun. 1158-59 (1986), and by Toyo Soda, (inventor:Kimura), J6 3014780-A (a published, but not yet examined, Japanese patent application). Additionally, auxiliary bases have used together with large excesses of macrocycle to obtain the mono-N-alkylation product by M. Studer et al., supra. Purification of the desired mono-N-alkylated product from the large excess of starting material and inorganic salt is a major problem associated with these methods. Additionally, the cost associated with employing a large excess of expensive reagent is prohibitive.
Other mono-N-alkylation attempts by F. Wagner et al., Inorg. Chem. 15, 408 (1976) involve selective deprotonation of a transition metal complex of a polyazamacrocycle with strong base followed by alkylation with methyl iodide. Further synthetic manipulation of this compound necessitates metal removal and purification which can be tedious.
Additional synthetic routes which afford mono-N-functional polyazamacrocycles involve lengthy, protection, functionalization, deprotection schemes which are divergent and not always general. For example, see P. S. Pallavincini et al., J. Amer. Chem. Soc. 109, 5139-44 (1987) and published European patent application 0 232 751 (1984).
In light of these limitations on mono-N-alkylation techniques existing in the art, it would be desirable to employ a direct alkylation approach which would not be reliant upon the use of excess macrocycle and an auxiliary base and yet would be selective for the desired mono-N-alkylated product.
Surprisingly, the present invention provides a process for preparing selectively the mono-N-alkylated products in a range of solvents without the use of large excesses of macrocycle and auxiliary base. The present process involves reacting between about one to five equivalents of a free base polyazamacrocycle with an appropriate electrophile in a solvent which will not promote a proton transfer.
The present invention is directed to a novel process for preparing a mono-N-alkylated polyazamacrocycle which comprises reacting an electrophile with between about one and five equivalents of a polyazamacrocycle in a solvent which will not promote a proton transfer. This process results in a greater selectivity for the desired mono-N-alkylated product compared to the bis, tris, tetra or higher N-alkylated products. The difficult and time consuming procedure of separating the excess starting material from the desired product and the commensurate cost involved in doing so is reduced when the essential features of this invention are used: (a) the possible and preferred use of about a one to one equivalent of electrophile to polyazamacrocycle and (b) the range of solvents possible to obtain the mono-N-alkylated product.
The present invention concerns the reaction of an appropriate electrophile (E) with a free base polyazamacrocycle (M) in a relatively non-polar, preferably aprotic solvent. The ratio of E to M is about one to five equivalents, preferably from about one to about three equivalents, more preferably from about one to about two equivalents, and most preferably from about one to about one equivalents.
The present process is very general and can produce selective mono-N-alkylation products with various polyazamacrocycles and electrophilies. A slight excess of polyazamacrocycle is preferred to insure complete conversion of the electrophile: however, only small differences in isolated yield occur when larger excesses of the polyazamacrocycle are used.
The term "polyazamacrocycles" as used in the present invention must contain at least two nitrogen atoms and at least one additional hetero atom and a methylene moiety, (--CH2)n, where n is from 2-4, as a spacer between the hetero atoms. The methylene moiety is independently selected between any two hetero atoms. The term "hetero atom" means a nitrogen, sulfur, or oxygen atom. Examples of polyazamacrocycles containing hetero atoms in addition to nitrogen are polyoxazamacrocycles or polythioazamacrocycles. Also included in the term polyazamacrocycles are any symmetrical rings such as polyazamacrocycle, azaoxamacrocycle or bicyclopolyazamacrocycle (i.e. bridged moieties or fused rings, but the mono-N-alkylation reaction occurs on the nitrogen atom of a saturated ring) which bears secondary amines capable of mono-N-alkylation. Preferably the secondary amines are all chemically equivalent. The macrocycle preferably has a plane of symmetry and the total number of hetero atoms (O, S, N) should preferably total an even integer. The combined total of hetero and carbon atoms in the polyazamacrocycle is preferably 12, 13, or 14. The term polyazamacrocycles means all of these heterocyclic possibilities and includes, for example, 1,3,7-triazacyclononane, 1,4,7,10-tetraazacyclododecane, 1,4,8,11-tetraazacyclotetradecane, 1,4,7,10,13-pentaazacyclopentadecane, 1,4,7,10,13,16-hexaazacyclooctadecane, 1,7,13-triaza-4,10,16-trioxacyclooctadecane, 1,7-diaza-4,10-dithiacyclododecane and the like.
The electrophile (RX) used in the present process is one capable of accepting a pair of electrons from one of the nitrogen atoms in the polyazamacrocycle. A covalent bond results from the reaction between the electrophile and polyazamacrocycle and selective mono-N-alkylation results. In the term RX, the R term is a C1 -C4 alkyl; a C1 -C4 alkyl which is substituted with a cyano, pyridinyl, CO2 R1 or CON(R1)2 moiety where R1 is H or C1 -C4 alkyl; or an alkylaryl where the alkyl portion is C1 -C4 and the aryl portion can be a 5 or 6 member carbon ring or a 9 member ring containing carbon and one or more hetero atoms selected from sulfur, nitrogen or oxygen. The X term is any leaving group. Such leaving groups are well known in the art such as, for example, chloro, bromo, iodo, acetate, trifluoroacetate, triflate, mesylate, diazo, brosylate and the like. Some suitable electrophiles are, for example, d,l-2-bromo-4-N-phthalamidobutanoic acid isopropyl ester, d,l-2 -bromo-4-(4-nitrophenyl)butanoic acid isopropyl ester, d,l-2-bromo-4-(4-nitrophenyl)butanoic acid methyl ester, 4-nitrocinnamyl bromide, 4-nitrophenethyl bromide, 4-nitrobenzyl bromide, benzyl bromide and the like.
Concentration of the reagents is not critical for the present process but for economic reasons and reasonable reaction times, the present process is preferably conducted under non-dilution conditions such as 1�10-3 M to 2M in each reagent. Mono-N-alkylations conducted under these concentrations afford the desired product in good to excellent yield with unexpectedly high selectivities. The mono-N-alkylated polyazamacrocycle is obtained in a selectivity of at least 40%, preferably from about 50 to about 98%, compared to the bis, tris and/or tetra N-alkylated products. The following schematic of p-nitrobenzyl bromide reacting with 1,4,7,10-tetraazacyclododecane illustrates what is meant by a mono, bis and tris alkylated product. While not wishing to be bound by theory, obtaining a predominantly mono-N-alkylated product is not expected if similar alkylation rates (e.g. kinetics) for the remaining nitrogens of the azamacrocycle are comparable to the rate constant for the first alkylation. ##STR1##
The solvent used for the present process is one which will not promote a proton transfer. Examples of suitable solvents which do not promote a proton transfer are (a) a polar, aprotic solvent: (b) a non-polar, aprotic solvent: or (c) a protic alcohol. Examples of suitable polar, aprotic solvents are, for example, chloroform (CHCl3), methylene chloride (CH2 Cl2), tetrahydrofuran, acetonitrile, 1,4,-dioxane or the like. Examples of suitable non-polar, aprotic solvents are, for example, carbon tetrachloride (CCl4), toluene, benzene, cyclohexane, n-hexane or the like. Examples of suitable protic alcohols are, for example, n-butanol, t-butanol, isopropanol, n-hexanol or the like. The term "aprotic" means that the solvent does not donate a proton to the reaction under the present process conditions. The term "protic alcohol" means a solvent which does not donate a proton to the reaction under the present process conditions although it contains a hydrogen attached to oxygen. The term "non-polar" means that the solvent possesses substantially little dipole moment, i.e., a dipole moment of less than 0.2 debyes.
Temperature employed is in the range of from about -78� C. to about 100� C., preferably from about -25� C. to about 40� C., more preferably from about 0� C. to about 25� C. The time of the reaction, at a temperature of from about 0� C. to about 25� C., is from about 10 to 24 hours. The time of the reaction will vary inversely with the temperature; however, the lower temperatures are preferred to aid in selectivity of the desired mono-N-alkylated product.
The absence of base from the displacement conditions of the reaction helps to prevent epimerization of chiral electrophillic reagents. Hence, optically active mono-N-alkylated adducts are potentially available by this present process. The product formed will possess the inverted optical form from the starting electrophile reagent. For example, the resulting mono-N-alkylated polyazamacrocycle product has the opposite optical configuration from the optically active α-haloacid ester.
The present process does not require the presence of an auxiliary base. Although trace amounts of such bases may be used, the process is conducted in the substantial absence of an inorganic auxiliary base such as, for example, sodium hydroxide, lithium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate and the like, or of an organic auxiliary base such as, for example, triethylamine, trimethylamine, pyridine, 4-N,N-diethylaminopyridine, diazobicyclododecane, diazobicyclononane and the like.
Furthermore, the absence of strong base and a low temperature allows for incorporation of other latent functionalities into the periphery of the polyazamacrocyole. For example, both ester and phthalamido functionalities are tolerant of the mild conditions of the present process. A procedure in the art [M. Studer et al., Helv. Chim. Acta. 69, 2081-86 (1986)] which employs lithium hydroxide in polar protic solvents such as aqueous ethanol or methanol may be expected to hydrolyze these groups.
The present process has been used to make valuable synthetic precursors to bifunctional chelator molecules for radioactive pharmaceuticals. [See our copending U.S. application Ser. No. 211,496 by S. Baughman et al., the disclosure of which is hereby incorporated by reference, our copending U.S. application Ser. No. 284,876 by J. Simon et al., the disclosure of which is hereby incorporated by reference, and our copending U.S. application Ser. No. 65,739 by W. J. Kruper et al., the disclosure of which is hereby incorporated by reference.] The brevity of the five step synthetic approach to these compounds, of which the present mono-N-alkylation step is critical, is superior to the nine step process for other pharmaceutical products. See, for example, M. K. Moi et al., J. Amer. Chem. Soc. 110, 6266-27 (1988).
The mono-N-alkylation process of this invention depends upon the availability of the desired electrophile. In the case of substituted α-haloacid esters, commercially available acids may be brominated and converted to an ester in a one pot, two step procedure using N-bromosuccinimide [see D. N. Harpp et al., J. Org. Chem. 40, 3420-27 (1975)]. This ionic bromination procedure is superior to the standard Hell-Vollard-Zelinski process and allows for exclusive alpha halogenation of alkanoic acids which contain even reactive benzyl groups. Optically active α-haloacids are readily available from the corresponding amino acids using recent advances in diazotization chemistry [see B. Koppenhoefer et al., "Organic Synthesis", Vol. 66, Ed. C. Heathcock, Pub. Wiley-Interscience, N.Y., pp. 151-57 (1988)]. Other electrophiles used in this invention may be prepared by procedures known in the art or can be purchased commercially.
The polyazamacrocycles such as 1,4,7,11-tetraazacyclododecane and similar cryptand ligands may be prepared by well documented methods which utilize a template effect in a multi-step procedure. For example see T. S. Adkins et al., J. Amer. Chem. Soc. 96, 2268-70 (1974). With advent of this versatile procedure, a number of these symmetrical macrocycles are now commercially available.
The invention will be further clarified by consideration of the following examples, which are intended to be purely exemplary of the use of this invention.
In the following examples, the equipment used was as follows:
Mass spectra were obtained on either a Finnigan
TSQ mass spectrometer or a VG ZAB-MS high-resolution mass spectrometer:
1 H and 13 C NMR spectra were obtained using a Varian VXR-300 spectrometer; and
IR were recorded on a Nicolet SSX FT/IR instrument.
In the following examples, all solvents were Fisher HPLC grade materials. All preparative chromatography of organic compounds was performed using flash chromatography techniques by W. C. Still et al., J. Org. Chem. 43, 2923-2925 (1978) and employed the following solvent systems:
Solvent System 1--CHCl3 :CH3 OH:conc. NH4 OH 2:2:1 (V:V:V);
Solvent System 2--CHCl3 :CH3 OH:conc. NH4 OH 12:4:1 (V:V:V); and
Solvent System 3--CHCl3 :CH3 OH:conc. NH4 OH 16:4:1 (V:V:V).
Rf values are reported using these solvent systems and commercially available silica plates.
1,4,7,10--Tetraazacyclododecane and 1,4,7,10,13-pentaazacyclopentadecane were purchased from Parrish Chemical Co.
1,4,8,11--Tetraazacyclotetradecane was purchased from Aldrich Chemical Co.
The following terms used in the examples are defined as follows:
conc. means concentrated; and
dec means decomposition.
Preparation of d,l-2-bromo-4-(4-nitrophenyl)butanoic acid methyl ester.
To a solution of 5 mL of carbon tetrachloride and 15 mL of thionyl chloride was added 10.46 g (0.05 mole) of 4-(4-nitrophenyl)butanoic acid under a nitrogen atmosphere. The solution was brought to reflux for one hour with initial rapid liberation of hydrogen chloride and sulfur dioxide. Following the gaseous liberation, 11.0 g (0.06 mole) of N-bromo-succinimide in 25 mL of carbon tetrachloride and 3 drops of 48% aqueous hydrogen bromide catalyst was added to the warm solution whereupon bromine liberation occurred. The dark red solution was refluxed for an additional 15 minutes, cooled and poured into 100 mL of methanol with stirring. TLC (60:40 ethyl acetate:n-hexane) indicated a product characterized by Rf =0.69. The excess solvent was removed and the dark red oil was filtered through a flash silica gel pad 1 in.�6 in. (2.5 cm�15.2 cm) using methylene chloride as the eluent. Evaporation of solvent gave 14.5 g of a colorless oil which was an 85:15 mixture of the title product:methyl ester of the starting material and was further characterized by:
1 H NMR (CDCl3)
δ8.16(d), 7.38(d), 4.20(dd), 3.79(s), 2.88(m);
13 C NMR (CDCl3)
δ169.6, 147.5, 129.3, 123.7, 53.0, 44.4, 35.5, 33.0.
Preparation of d,l-2-bromo-4-(4-nitrophenyl)butanoic acid isopropyl ester.
The title ester was obtained as a clear oil in 50% yield after quenching the crude acid chloride with isopropanol and chromatographic purification. The product (Rf =0.73, methylene chloride) was devoid of any unbrominated ester and was further characterized by:
1 H NMR (CDCl3)
δ8.16(d), 7.38(d), 5.05(septet), 4.14(dd), 2.88(m), 2.39(m), 1.29(d);
13 C NMR (CDCl3)
δ168.7, 147.7, 129.3, 123.8, 69.9, 45.1, 35.6, 33.0, 21.5, 21.2.
Preparation of trans-p-nitrocinnamyl bromide.
In 35 mL of dry acetonitrile under nitrogen atmosphere was added 7.3 g (27.9 mmole) of triphenylphosphine. To the solution was added dropwise over 15 minutes 4.31 g of bromine (27.0 mmole) while cooling the reaction mixture to maintain the temperature between 0�-10� C. The solution was allowed to warm to room temperature (about 22�-25� C.) and 5.0 g (27.9 mmole) of p-nitrocinnamyl alcohol (Pfaultz & Bauer Chemical Co.) was added as a slurry in 50 mL of acetonitrile which caused an exothermic reaction, temperature about 45� C. The resulting dark red solution was heated for one hour at 60� C. with stirring and then poured into 500 mL of ether. Triphenylphosphine oxide precipitated from the solution after standing overnight (about 16 hours). The solution was filtered and 15 g of flash silica gel was added to the solution, followed by solvent removal. The resulting powder matrix was applied to a 3 in.�8 in. (7.6 cm�20.3 cm) flash column and the desired product was eluted with hexane, followed by 20% ethyl acetate in hexane to yield 5.8 g (23.9 mmole) of the desired pure trans product in 86% yield (MP=75�-76� C., Rf =0.81, 60:40 ethyl acetate:n-hexane) and was further characterized by:
1 H NMR (CDCl3)
δ8.17(d), 7.51(d), 6.70(dd), 6.56(dt), 4.16(dd);
13 C NMR (CDCl3)
δ147.3, 142.1, 132.0, 129.8, 127.2, 123.9, 31.8.
Preparation of d,l-2-bromo-4-(N-phthalamido)butanoic acid isopropyl ester.
Into a flask equipped with a trap and water condenser was placed 14.8 g (100 mmole) of phthalic anhydride, 10.3 g (100 mmole) of Y-aminobutyric acid (Aldrich Chemical Co.), 1.3 mL of triethylamine and 150 mL of toluene. The mixture was brought to reflux and 1.75 mL of water was removed azeotropically over 1.5 hours. The solution was allowed to cool and stand overnight (about 16 hours). The resulting white crystals that formed were filtered, washed with hexane and dried. The crude crystals were then washed with 250 mL of 5% aqueous hydrogen chloride and 100 mL of cold water. After drying, 19.0 g (81.5 mmole) of 4-(N-phthalamido)butanoic acid was obtained in 82% yield (MP=114.5�-115.5� C., recrystallized from 30% methanol in water) and further characterized by:
1 H NMR (CDCl3)
7.84(dd), 7.72(dd), 6.05(bs), 3.77(t), 2.42(t), 2.02(p);
13 C NMR (CDCl3)
δ177.9, 169.4, 134.0, 123.3, 37.1, 31.2, 23.6.
The above prepared 4-(N-phthalamido)butanoic acid was reacted by the procedure of Example A and B to obtain the title ester as a white solid, yield 68%, (MP=72�-4.5� C., Rf =0.38, chloroform) after flash silica gel chromatography using chloroform as an eluant, and further characterized by:
1 H NMR (CDCl3)
δ7.85(dd), 7.73(dd), 5.04(septet), 4.23(dd), 3.85(dt), 2.51(m), 2.36(m), 1.29(d), 1.26(d).
Preparation of 1,4,7,10-tetraaza-1-[(4-nitrophenyl)methyl]cyclododecane.
The free base, 3.5 g (20.3 mmoles), of 1,4,7,10-tetraazacyclododecane and 1.7 g (7.87 mmoles) of p-nitrobenzyl bromide (a polyazamacrocycle to electrophile ratio of about 2.5:1) in 50 mL of chloroform were stirred under nitrogen for 24 hours at 25� C. The chloroform slurry of hydrobromide salt was then applied to a 1 in.�17 in. (2.5 cm�43.2 cm) column of flash silica gel (Solvent System 3). The product, 2.13 g (6.93 mmoles) was obtained as a pale yellow solid (MP=128�-29� C., Rf =0.58
Solvent System 3) in 88% yield and further characterized by:
1 H NMR (CDCl3)
δ8.18(d), 7.49(d), 3.69(s), 2.82(t), 2.70(t), 2.59(m);
13 C NMR (CDCl3)
δ147.2, 128.4, 123.8, 58.8, 51.7, 47.1, 46.3, 45.1.
Preparation of 1,4,7,10-tetraaza-1-[2-(4-nitrophenyl)ethyl]cyclododecane.
To a stirred solution of 3 5 g (20.3 mmole) of 1,4,7,10-tetraazacyclododecane in 50 mL of pentene stabilized chloroform was added dropwise over five minutes with vigorous stirring under a nitrogen atmosphere 4.0 g (17.4 mmoles) of 1-bromo-2-(4-nitrophenyl)ethane (Aldrich Chemical Co.). This constituted a polyzazmacrocycle to electrophile ratio of about 1.2:1. The stirring was continued overnight at about 25� C. whereupon crystals of amine hydrobromide precipitated from solution. The contents of the flask were applied to a flash silica gel column 1 in.�18 in. (2.5 cm�45.7 cm) which had been pre-eluted with 5% methanol in chloroform and 200 mL of this solution was applied as an eluent, followed by elution with Solvent System 3. The p-nitrostyrene (1.45 g, 9.7 mmole, Rf =0.98, Solvent System 2) was cleanly separated from 2.27 g (7.06 mmole) of the desired product as an orange yellow oil (yield 40.6%) which solidified upon standing (Rf =0.73, Solvent System 2). A sample was recrystallized [MP=146.5�-148.5� C. (dec)] from chloroform/cyclohexane and was further characterized by:
1 H NMR (CDCl3)
δ8.14(d), 7.40(d), 2.91(t), 2.77(t), 2.72(t), 2.50(t), 2.60(s);
13 C NMR (CDCl3)
δ148.5, 129.6, 123.4, 55.5, 51.4, 46.9, 45.9, 45.1, 33.7.
Preparation of 1,4,7,10-tetraaza-1-[1-carbomethoxy-3-(4-nitrophenyl)propyl]cyclododecane.
To a stirred solution of 1.72 g (10.0 mmole) of 1,4,7,10-tetraazacyclododecane in 17 mL of pentene stabilized chloroform was added 2.07 g (5.82 mmole) of crude d,l-2-bromo-4-(4-nitrophenyl)butanoic acid methyl ester (prepared by the procedure of Example A) over a five minute period under a nitrogen atmosphere. This constituted a polyazamacrocycle to electrophile ratio of about 1.7:1. The reaction mixture was stirred for 48 hours at about 25� C. and TLC (Solvent System 2) indicated the conversion to the desired monoalkylation product (Rf =0.73, ninhydrin, iodine, and UV active). The yellow chloroform solution was applied to a 1 in.�16 in. (2.5 cm�40.6 cm) flash silica gel column which had been preeluted with 5% methanolic chloroform, followed by elution with 250 mL of the preelution solvent system, and then elution with Solvent System 2. The fractions containing the desired product were combined and evaporated affording 2.15 g (5.46 mmole) of the desired.. product (MP=156�-159� C., recrystallized from chloroform, ether) in 94% yield and further characterized by:
1 H NMR (CDCl3)
δ8.14(d), 7.39(d), 3.71(s), 3.39(dd), 2.5-3.0(m), 2.08(m), 2.01(m);
13 C NMR (CDCl3)
δ172.7, 149.3, 146.4, 129.2, 123.6, 62.3, 51.2, 48.9, 47.2, 45.8, 45.4, 32.8, 30.9.
Preparation of 1,4,7,10,13-pentaaza-1-[1- carboisopropoxy-3-(4-nitrophenyl)propyl]-cyclopentadecane.
By the procedure of Example 3, one equivalent of 1,4,7,10,13-cyclopentadecane was reacted with one equivalent of d,l-2-bromo-4-(4-nitrophenyl) butanoic acid isopropyl ester. This constituted a polyazamacrocycle to electrophile ratio of about 1:1.
The purified desired product was obtained as a light yellow oil in 77% yield after chromatography on silica gel (Rf =0.82, Solvent System 2) and further characterized by:
1 H NMR (CDCl3)
δ8.14(d), 7.49(d), 5.09(septet), 4.86(s), 3.38(dd,s), 2.5-3.0(m), 2.30(m), 2.11(m), 1.29(d);
13 C NMR (CDCl3)
δ171.9, 149.1, 146.5, 129.5, 123.6, 68.7, 61.9, 49.5, 46.8, 46.7, 45.5, 45.3, 32.9, 32.1, 22.1, 22.0;
IR (CDCl3) cm-1
3450, 2860, 1735, 1350, 915.
Yields of mono-N-alkylation of p-nitrobenzyl bromide (Aldrich Chemical Co.) with 1,4,7,10-tetraazacyclododecane are given in Table 1. The results clearly show the mono-N-alkylated product is obtained preferentially over the bis and tris alkylated products and that the ratio of M:E is from about 1:1 to 1:2.
TABLE I__________________________________________________________________________Ex. [E] % ISOLATED YIELD**No. M:E MOLARITY SOLVENT MONO BIS TRIS MONO:BIS__________________________________________________________________________5A 1:1.0 1 CHCl3 49 11 5 4.5:15B 1:1.5 1 CHCl3 66 10 3 6.6:15C 1:1.5 4 � 10-2 CHCl3 73 9 2 7.4:15D 1:1.5 1 CH3 OH 39 16 3 2.4:15E 1:1.5 1 CH3 (CH2)3 OH 43 15 3 3.0:1A* 1:1.5 1 CH3 OH*** 34 19 7 1.8:1__________________________________________________________________________ *A is not a process of the invention. **Isolated yield of product after flash chromatography; process at 25� C. ***1.0 equivalents of KCO3 added relative to bromide.
Preparation of various mono-N-alkylpolyazamacrocycles using the process of the invention.
In Table II following, various electrophiles were reacted with polyazamacrocycles which gave yields greater than 40% selectivity for the desired mono-N-alkylpolyazamacrocycle, expressed as percent (%) isolated yield. The process was run using the equivalents and solvents given in Table II and by the procedure of Examples 1-4. Table III following indicates the structure of the desired mono-N-alkylpolyazamacrocycle formed by the reaction in Table II.
TABLE II__________________________________________________________________________ % MACROCYCLE ISOLATEDEX. ELECTROPHILE (EQ) SOLVENT YIELD* MONO:BIS__________________________________________________________________________6A ##STR2## ##STR3## (2.0) CHCl3 1006B ##STR4## ##STR5## (1.0) CHCl3 50 4.5:16C ##STR6## ##STR7## (2.0) CHCl3 87 10:16D ##STR8## ##STR9## (1.1) CHCl3 43** >20:16E ##STR10## ##STR11## (1.0) CHCl3 816F ##STR12## ##STR13## (1.7) CHCl3 946G ##STR14## ##STR15## (1.7) CCl4 706H ##STR16## ##STR17## (1.7) THF 866I ##STR18## ##STR19## (1.5) CHCl3 616J ##STR20## ##STR21## (1.5) CHCl3 646K ##STR22## ##STR23## (1.2) CHCl3 586L ##STR24## ##STR25## (1.2) CHCl3 69 4.1:16M ##STR26## ##STR27## (1.1) CHCl3 83 34:1__________________________________________________________________________ *Flash chromatography purification based upon electrophile as limiting reagent (1.0 eq.) **p-nitrostyrene isolated in 54% yield
Other embodiments of the invention will be apparent to those skilled in the art from a consideration of this specification or practice of the invention disclosed herein. It is intended that the specification and examples be considered as exemplary only, with the true scope and spirit of the invention being indicated by the following claims:
|Cited Patent
|Filing date
|Publication date
|Jan 19, 1987
|Aug 19, 1987
|E.R. Squibb & Sons, Inc.
|1-substituted-4,7,10-triscarboxymethyl-1,4,7,10-tetraazacyclododecane and analogs
|Title not available
|E. Kimura et al., J. Chem. Soc. Chem. Commun., 1158 1159 (1986).
|E. Kimura et al., J. Chem. Soc. Chem. Commun., 1158-1159 (1986).
|F. Wagner et al., Inorg. Chem. 15, 408 417 (1976).
|F. Wagner et al., Inorg. Chem. 15, 408-417 (1976).
|M. Studer et al., Helv. Chim. Acta. 69, 2081 2086 (1986).
|M. Studer et al., Helv. Chim. Acta. 69, 2081-2086 (1986).
|P. S. Pallavincini et al., J. Amer. Chem. Soc., 109, 5139 5144 (1987).
|P. S. Pallavincini et al., J. Amer. Chem. Soc., 109, 5139-5144 (1987).
|T. A. Kaden, Top Curr. Chem. 121, 157 179 (1984).
|T. A. Kaden, Top Curr. Chem. 121, 157-179 (1984).
|Citing Patent
|Filing date
|Publication date
|Feb 11, 1993
|Jan 31, 1995
|Schering Aktiengesellschaft
|Process for the production of N-β-hydroxyalkyl-tri-N-carboxyalkyl-1,4,7,10-tetraazacyclododecane and N-β-hydroxyalkyl-tri-N-carboxyalkyl-1,4,8,11-tetraazacyclotetradecane derivatives and their metal complexes
|Oct 25, 1993
|Apr 25, 1995
|Schering Aktiengesellschaft
|Process for the production of mono-N-substituted tetraaza macrocycles
|Oct 22, 1993
|Jun 27, 1995
|The United States Of America As Represented By The Department Of Health And Human Services
|Complexes of functionalized tetraazacyclododecane chelates with bismuth, lead, ytriium, actinium, or lanthanide metal ions
|Jun 7, 1995
|May 20, 1997
|Nycomed Imaging As
|Polyazacycloalkane compounds
|Feb 2, 1995
|Jun 17, 1997
|Associated Universities, Inc.
|Macrocyclic polyaminocarboxylates for stable radiometal antibody conjugates for therapy, spect and pet imaging
|Jun 7, 1995
|Oct 14, 1997
|Nycomed Imaging As
|Polyazacycloalkane compounds
|Feb 3, 1997
|Jan 6, 1998
|Nycomed Imaging As
|Polyazacycloalkane compounds
|Aug 16, 1996
|Nov 2, 1999
|Neumann; William L.
|Methods of diagnostic image analysis using metal complexes of nitrogen-containing macrocyclic ligands
|Sep 28, 2001
|Dec 3, 2002
|Anormed, Inc.
|Process for preparation of N-1 protected N ring nitrogen containing cyclic polyamines and products thereof
|Dec 17, 1999
|Jan 28, 2003
|Bristol-Myers Squibb Pharma Company
|Vitronectin receptor antagonist pharmaceuticals
|Jun 21, 2000
|Jan 28, 2003
|Thomas D. Harris
|Vitronectin receptor antagonist pharmaceuticals
|Mar 30, 1999
|Feb 25, 2003
|Bristol-Myers Squibb Pharma Company
|Quinolone vitronectin receptor antagonist pharmaceuticals
|Jun 21, 2000
|Mar 25, 2003
|Bristol-Myers Squibb Pharma Company
|Pharmaceuticals for the imaging of angiogenic disorders
|Mar 30, 1999
|Apr 15, 2003
|Bristol-Myers Squibb Pharma Company
|Benzodiazepine vitronectin receptor antagonist pharmaceuticals
|Dec 17, 1999
|May 6, 2003
|Bristol-Myers Squibb Pharma Company
|Vitronectin receptor antagonist pharmaceuticals
|Jun 21, 2000
|May 27, 2003
|Bristol-Myers Squibb Pharma Company
|Vitronectin receptor antagonist pharmaceuticals
|Sep 7, 2001
|Jan 27, 2004
|Bristol-Myers Squibb Pharma Company
|Vitronectin receptor antagonist pharmaceuticals
|Sep 7, 2001
|Feb 10, 2004
|Bristol-Myers Squibb Pharma Company
|Vitronectin receptor antagonist pharmaceuticals
|Sep 7, 2001
|Jun 1, 2004
|Bristol-Myers Squibb Pharma Company
|Vitronectin receptor antagonist pharmaceuticals
|Dec 17, 1999
|Sep 21, 2004
|Bristol-Myers Squibb Pharma Company
|Vitronectin receptor antagonist pharmaceuticals
|Nov 26, 2002
|Nov 16, 2004
|Bristol-Myers Squibb Pharma Company
|Vitronectin receptor antagonist pharmaceuticals
|Aug 7, 2002
|Jan 4, 2005
|Bristol-Myers Squibb Company
|Simultaneous imaging of cardiac perfusion and a vitronectin receptor targeted imaging agent
|May 17, 2001
|Apr 12, 2005
|Bristol-Myers Squibb Pharma Company
|Use of small molecule radioligands to discover inhibitors of amyloid-beta peptide production and for diagnostic imaging
|Oct 26, 2002
|Mar 28, 2006
|Bristol-Myers Squibb Pharma Company
|Vitronectin receptor antagonist pharmaceuticals
|Jul 18, 2003
|May 30, 2006
|Bristol-Myers Squibb Pharma Company
|Pharmaceuticals for the imaging of angiogenic disorders
|Aug 21, 2003
|Jun 13, 2006
|Bristol-Myers Squibb Pharma Company
|Matrix metalloproteinase inhibitors
|Jan 21, 2003
|Aug 15, 2006
|Bristol-Myers Squibb Pharma Company
|Vitronectin receptor antagonist pharmaceuticals
|Aug 7, 2002
|Nov 21, 2006
|Bristol-Myers Squibb Company
|Simultaneous imaging of cardiac perfusion and a vitronectin receptor targeted imaging agent
|Feb 2, 2004
|Jan 22, 2008
|Bristol-Myers Squibb Pharma Company
|Vitronectin receptor antagonist pharmaceuticals
|Jun 21, 2000
|Feb 19, 2008
|Bristol-Myers Squibb Pharma Company
|Vitronectin receptor antagonist pharmaceuticals
|Feb 7, 2003
|Oct 7, 2008
|Covalent Partners, Llc
|Nanofilm and membrane compositions
|Jan 8, 2009
|Jan 29, 2013
|Lantheus Medical Imaging, Inc.
|N-alkoxyamide conjugates as imaging agents
|Dec 21, 2012
|Oct 7, 2014
|Lantheus Medical Imaging, Inc.
|N-alkoxyamide conjugates as imaging agents
|Jul 8, 2010
|Nov 4, 2014
|Lantheus Medical Imaging, Inc.
|N-alkoxyamide conjugates as imaging agents
|Sep 2, 2014
|Feb 23, 2016
|Lantheus Medical Imaging, Inc.
|N-alkoxyamide conjugates as imaging agents
|Sep 22, 2014
|Jul 19, 2016
|Lantheus Medical Imaging, Inc.
|N-alkoxyamide conjugates as imaging agents
|May 17, 2001
|Oct 31, 2002
|Robert Zaczek
|Use of small molecule radioligands to discover inhibitors of amyloid-beta peptide production and for diagnostic imaging
|Aug 7, 2002
|Jun 5, 2003
|Carpenter Alan P.
|Simultaneous imaging of cardiac perfusion and a vitronectin receptor targeted imaging agent
|Oct 26, 2002
|Jun 19, 2003
|Harris Thomas D.
|Vitronectin receptor antagonist pharmaceuticals
|Oct 11, 2002
|Jul 3, 2003
|Harris Thomas D.
|Quinolone vitronectin receptor antagonist pharmaceuticals
|Nov 26, 2002
|Jul 31, 2003
|Cheesman Edward H.
|Vitronectin receptor antagonist pharmaceuticals
|Aug 23, 2002
|Oct 23, 2003
|Josh Kriesel
|Macrocyclic module compositions
|Jan 21, 2003
|Jan 22, 2004
|Cheesman Edward H.
|Vitronectin receptor antagonist pharmaceuticals
|Apr 29, 2003
|Jun 3, 2004
|Kriesel Joshua W.
|Nanofilm compositions with polymeric components
|Feb 7, 2003
|Dec 23, 2004
|Kriesel Joshua W.
|Nanofilm and membrane compositions
|Sep 1, 2004
|May 19, 2005
|Harris Thomas D.
|Compounds containing matrix metalloproteinase substrates and methods of their use
|Feb 2, 2004
|Jul 14, 2005
|Bristol-Myers Squibb Pharma Company
|Vitronectin receptor antagonist pharmaceuticals
|Aug 1, 2005
|Dec 29, 2005
|Bristol-Myers Squibb Pharma Company
|Matrix metalloproteinase inhibitors
|Jul 18, 2003
|Jan 5, 2006
|Milind Rajopadhye
|Pharmaceuticals for the imaging of angiogenic disorders
|Jun 28, 2006
|Jan 18, 2007
|Harris Thomas D
|Hydrazide conjugates as imaging agents
|Jan 8, 2009
|Oct 8, 2009
|Lantheus Medical Imaging, Inc
|N-alkoxyamide conjugates as imaging agents
|Sep 28, 2001
|Feb 11, 2009
|Anormed Inc.
|Process for the preparation of N-1 protected N ring nitrogen containing cyclic polyamines and products thereof
|U.S. Classification
|540/474, 540/467
|International Classification
|Cooperative Classification
|European Classification
|Jun 27, 1991
Owner name: DOW CHEMICAL COMPANY, THE, A CORP. OF DE, MICHI
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST.;ASSIGNOR:KRUPER, WILLIAM J., JR.;REEL/FRAME:005751/0465
Effective date: 19900709
|Jun 22, 1993
|Certificate of correction
|Jan 12, 1995
|Fee payment
Year of fee payment: 4
|Mar 2, 1999
|Fee payment
Year of fee payment: 8
|Apr 14, 2003
|Fee payment
Year of fee payment: 12


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You are here: Home | Melbourne Sightseeing
So you have done some Sightseeing and you would love to share your amazing story with someone...
Well you can!
Here on this website you can write your story and tell everyone what it is that impressed you so much.
Things like...
Sightseeing On The Streets Of Melbourne
There are so many Melbourne sightseeing tourist attractions, I know because I have seen most of them. However for those who are still looking around at what they might do with the family I am sure that what you have to share will be appreciated.
Have you been to Luna Park, down St Kilda way.
Great family fun and full of thrilling rides for the kids.
Tell us all about it here.
Luna Park Amusement Center - St Kilda
Straight from the horses mouth as they say. Been there-done that sort of experience, nothing like it. Your personal recommendation to us all.
Just below here you will find a form that is very easy to use. Just fill in the details of your personal Melbourne Australia experience.
If you have some photos add them to the story...I love pictures!
This one was taken by my friend Steve Curle at the Melbourne Docklands during one of Melbourne's great Fire and Light celebrations.
Fire And Light Show Docklands - Melbourne Australia
Did you go somewhere special?
Did you find that little unknown, magic, secret place?
Do you know of a unique place to shop in Melbourne?
How did you find it? Where was it?
Tell us your story. Why did you like it so much?
Click on the links below to see some fascinating stories about other people's great times in Melbourne . They were all written by other visitors to this page.
Belgrave South Community Market
The Belgrave South Community Market is coordinated by Indie Market Place . The market runs every 1st Sunday of the Month in the heart of Belgrave …
Summer Night Markets - Warrnambool
We are in the beautiful South Western Victoria. A series of wonderful markets held predominantly over summer in Warrnambool. Fabulous & unique stalls, …
Eating Singapore Street Style
GF (Gluten Free) Pizza
Plus Afternoon Tea!
On my first visit to Melbourne, a girly trip with my Mum, one of the things which struck me most was the wonderful array of different restaurants …
Holiday In Melbourne
Dreaming About Going Back
My wife and I were having a bit of a think about where we'd go to celebrate our 25th wedding anniversary. Just the two of us for a change. We'd …
Get the free City Tram for the Ice House Not rated yet
If you're visiting the skating rink at the Ice House, it is best not to follow the instructions on their website. The suggested walking route from Spencer …
Puffing Billy - Melbourne Australia Not rated yet
Day 2 of our Host Family Excursions saw us all up high in the Dandenong Ranges . Here we boarded the Puffing Billy Locomotive at Emerald Lake railway …
Tooradin Ice Cream Shop Not rated yet
This is our first time playing at being a Host Family for a young Japanese Student, Shu. He is staying with us for 12 nights so this weekend we decided …
South Melbourne Market Not rated yet
Today we went to South Melbourne Market. It was a fantastic morning just wandering down the various aisles looking from left to right seeing what …
Thanks for sharing your happy memories with us all.
Please note that some links on this page are to companies that I have an affiliation with. By that I mean that if you purchase a product through them I receive a very small commission. This way of earning income is termed Monetization and it is a way for me to keep my site out here for you to enjoy. I will only affiliate with companies that I feel offer value for money and excellent back up service. These are Companies that I personally have used to purchase products for myself, my family and my friends. To learn more please refer to my Disclaimer page
Use this to check the UV in your area, click on the down arrow for location closest to you
Be Sun Smart
You cannot feel or see UV (Ultraviolet radiation). We can see the sun's light and we can feel the sun's warmth (the infrared radiation). Our senses don't pick up on UV radiation and this is why it is so damaging.
Right across Australia this UV radiation varies, it being determined by the time of day, time of year, the weather including cloud cover, how close to the equator the position is and other considerable scientific factors.

subset: commoncrawl


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Rock Hill, S.C. – July 7, 2016 – Gabriel Performance Products (Gabriel), a market leader in epoxy additives and specialty chemical manufacturing, has expanded their sales team to support development and growth of the Versamid® product family. Versamid includes various liquid epoxy curing agents, including reactive polyamides (modified and unmodified), amidoamines and selected modified amine curing agents.
The Versamid product family is a key brand in Gabriel's strategy to expand our specialty proprietary product offering within the coatings, adhesives, sealants, and elastomers markets," said Gabriel Performance Products' Vice President of Sales, Marianne Riemer. "We expanded our sales team to help drive the growth of Gabriel, with the initial focus on the Versamid brand."
Riemer adds, "I am happy to announce that all Versamid products have been commercially produced, and are available for sampling and order fulfillment." Gabriel recently acquired all remaining stock of product previously produced by BASF, and these products are available for purchase until supplies are exhausted.
Read More HERE
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2/23/2017Thermal Imaging Helps Chemicals Company to Monitor Package Sealing Quality
2/22/2017Covestro LLC Sells Spray Polyurethane Foam Business to Accella
3/15/2017Toughening Technologies for Structural Adhesives Webinar
4/3/2017 » 4/4/20172017 Waterborne Adhesives Short Course


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Fish - Cyanide & Happiness Shorts
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This Gif entitled Fish - Cyanide & Happiness Shorts was created from the youtube video 2 years ago. It uses 18 frames per second and is displayed at 640px resolution. This animated image plays for 1 seconds, was built with high quality and an estimated weight of 1.78 MB for download. This animation was originally created from the Fish - Cyanide & Happiness Shorts video from 00:10 to 00:11.
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hope you get to get started soon katrea
dh and i seen dr smith last thursday it was our first appt with him and all went well but we never got billed for this appt ???? we are so confused lol dont get me wrong i was happy to come home with my $380 but do they bill you later or something ??has this happened to anyone before ??
atm i am waiting to hear back from the nurses to make our appt with them and should be able to start pill popping in jan if they let me


text:
× View Today's Deals
You missed it This great deal for Just Teasin' Hair Salon is over. But don't despair, we've got more great deals every day.
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Just Teasin' Hair Salon
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You'll instantly feel at home in this Indianapolis salon, which boasts hip décor and friendly stylists eager to help you achieve your desired look:
• $50 ($100 value) for a haircut, deep conditioning, partial highlights, and blow dry
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PAID VALUE EXPIRES ON February 21, 2022
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What a great smooth labour! It's so nice to hear of a great experience
He is such a bunny - congratulations!
What a great smooth labour! It's so nice to hear of a great experience
He is such a bunny - congratulations!
Wow - look at all that hair!!! So cute Well done
"...dreaming of a belly full of life"
Can't wait he is beautiful! How amazing is his hair! You look amazing too! What a great labor, so happy it went just as you wanted, fantastic! Zac is on our short short list! Great taste!
Welcome to the world zac, and welcome to motherhood can't wait.
Awwww thanks everyone! It feels like I am in a dream, everything is just going so smoothly and I couldn't ask for more. He is such a good boy, sleeping and feeding like a little champion at the moment
Good luck to everyone trying at the moment and especially to those who have been trying for a while, any wait you have to endure is going to pay off ten fold when you eventually hold your precious baby in your arms, stay strong and lots of baby dust to you guys .
Disney I bet you are getting so excited with only 6 weeks to go! The time can feel like forever but before you know it you will get to your due date woohoo bring it on, looking forward to finding out if you have a boy or girl brewing in there!
Lil Nightmare - Draven looks so cute, can't believe he is over 2 weeks old already! I hope everything is going well for you and he is letting you get some good sleep.
Cantwait congrats in zac! He is adorable and the hair omg I thought draven had some hair. Your labour sounded like it went great. Enjoy your mummy time. I can't believe how quick it's going.
You're next Disney!
Cantwait, a big congratulations to you! Zac is so cute. Look at all the hair. So glad to hear things have been going well!
Disney, I think you will have a girl. Only because the thread already has two boys!
Cantwaitforabubba (15-10-2013),Disney (13-10-2013)
congrats can't wait he is a gorgeous baby. Good to hear that all is going so well already.
What did everyone get up too on the weekend?
We started construction on a fort for ds, it has been so much fun planning all the cool fun things we can put in it! A basic frame is cemented into the ground, but we still need to add more frame work for the roof and walls.
Stressed myself out about toxoplasmosis. I don't even know if I am pregnant or not, I just hate the neighbours cats pooing in our yard. I was playing in ds sand pit and scooped a great big crap out with cup, so gross! And the sandpit gets covered every night. That went to the tip, and I now refuse to have a sand pit. There's just too many cats here. It's not fair!
DH & I had dinner & went for a romantic walk by the lakes where we live when the weather was beautiful on saturday...and we also bought an A/C! Going to need it I think when I'm having a homebirth in January.
I'm not worried about toxoplasmosis, I assume I'm immune to it having worked with cats for 7 years and having pet cats for about 6.5 years. As long as you wash your hands well after handling cat poo, raw meat etc you should be fine. I don't blame you for getting rid of the sandpit, my parents had the same problem when we were kids. They covered it up which seemed to keep the cats out but then bush rats moved in instead!
You'll have to post a pic of the fort when you're done!
Sent from my GT-I9305 using The Bub Hub mobile app
Pregnant for the first-time?
Not sure where to start? We can help!
Our Insider Programs for pregnancy first-timers will lead you step-by-step through the 14 Pregnancy Must Dos!


text:
Villa Rosmarino
No prices found through our partners. Please contact the business directly or check some of our recommended alternatives.
How has this b&b rated in the past?
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Camogli and Recco
... swim a lot because it was our second to last practice before we return home.
As we stretched we became more determined and focused on practice. After our warm-up we began the awaiting brutal swim set. Swim set: 4x100, 2x200, 4x100, 8x50, 16x25's all sprint. After the exhausting swim set began the hardest leg set of the trip, 15 minutes straight of leg work with hands out doing various maneuvers. Following legs we started passing and shooting, then concluded practice with ...
Cinque Terre or Cinque Terror
... easy someone in a wheelchair can walk it. It is a section called "Via dell'Amore" and seeing we are celebrating our wedding anniversary it is appropriate, only trouble is this section is closed for renovation.
So we decide to catch a ferry to the next port of Manarola, but not much to see here just hoards of tourists walking around waiting for the next train to the middle town of Corniglia which is not accessable by ferry. We get off the train and find ...
Rapallo, Portofino e Cinque Terre
... br> Hark, now hear the sailors cry
Smell the sea and feel the sky
Let your soul and spirit fly
Into the mystic
And when that fog horn blows
I will be coming home
And when the fog horn blows
I want to hear it, I don't have to fear it
I want to rock your gypsy soul
Just like way back in the days of old
And magnificently we will fold
Into the ...
A Lot of Hills in A Lot of Towns
Today was so much fun!!!! We traveled to four little villages in the Cinque Terre and each town had something great to offer. It was also the first time that I rode a train and let me say that it wasn't as bad as I thought it would be. The people in these villages were so nice and they all knew each other. I enjoyed watching them all interact with each other. Our group was really the only one ...
Riomaggiore and Manorola today
... saint and the fireworks, will get a good view from our room. Wow a thunderstorm even hail, hope they covered up the fireworks. Not a good choice for dinner expensive and no extras. Rod had prawns and got 4 big prawns, nothing else on the plate. I had swordfish and I got two slices of swordfish nothing else, not even a bit of parsley. Storm has all cleared. But they packed up the ...


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In response to the federal listing of Lynx as threatened, Maine's Department of Inland Fisheries and Wildlife restricted trapping in the Lynx's region. But animal rights groups have been complaining ever since, especially about the decision by the feds to give Maine an incidental take permit, allowing a few Lynx to be accidentally captured. A lot of this battle has been fought in court.
In August 2015, wildlife and animal welfare groups, including the Center for Biological Diversity, Wildlife Alliance of Maine and the Animal Welfare Institute, sued the U.S. Fish and Wildlife Service for allegedly failing to enforce rules protecting Canada lynx from being killed or injured.


text: Petit Bateau Petit Bateau Fancy jersey Onesies See all details Petit Bateau From $AU 25 From $AU 25 From $AU 25 From $AU 25 From $AU 25 Color: White Size: Size guide Choose your size. 1 month - (out of stock) 3 months - (out of stock) 6 months - (out of stock) 12 months - $AU 25 Size available soon Alert me when this product is available Alert me Choose your size. Pre-order : Available soon Add to basket Buy the look The item has been added to your wishlist Your item has been added to your gift list Share on Facebook Share on Twitter (@Melijoe_Fashion) Pin on Pinterest Share on Google Plus Share on Weibo Share on VK Delivery: 3 working days Details Description Cotton jersey Polo collarShort sleevesSnap buttons at the back and on the crotchFront printSmall logo patch on the pocket Reference16437-01 General details Jersey:100% CottonMachine washable at 30°C.


text:
Release Date: 2009 |
Album Rating: 4.0Choice cuts:
Peter Pan Complex
Empty Nest
Digging: Departures - Death Touches Us, From The Moment We Begin To Love
I missed the soundoff reviews
Digging: The Menzingers - After the Party
Album Rating: 4.0This is my shortest so far
Let's see if I can get down to like 1 line
Album Rating: 3.0yeah you summed it up
Digging: boring bathtimes - Loss
fuck that was short
Digging: Funeral Diner - The Underdark
Album Rating: 3.5I've never thought this album was that special
Album Rating: 4.0It's not really
I'd give it a 3.7 or 3.8 if I could
This is good stuff.
agreed on everything except the rating but you know
actually pretty sure these guys are from Charm City I'd probably give them a bump just cuzza that
Super short review, but fitting.
Album Rating: 4.0Such an enjoyable jam!
Bands: A B C D E F G H I J K L M N O P Q R S T U V W X Y Z


text:
Please help us to describe the issue so we can fix it asap.Cancel
Ji Yun visits Hyo Sang's house and opens Hyo Won's door. Hyo Won runs to meet Tae Yang and stays in hostel for a night. Meanwhile, Yun Shil confesses her love for Dong Jin to Gi Pyo's mum while Dong Sook and Tae Pyung tell everyone about their plan for marriage.


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Just a few of the blatent lies from our current commander and chief during the debates:<quoted text>
That's really hilarious coming from someone who's shilling for the most mendacious individual ever to seek the presidency and his equally dishonest running mate.
In Tuesday's debate he came up with a whole new lie in that he actively sought qualified women after he was elected governor and as a result of that request received "binders full of women". The group that gave him this list of women, MassGAP, made it up well before the election and presented it to him when he was elected. He never requested this information.
www.nydailynews.com/.../mitt-a-bind-weird-deb... ....
But that's only one of several falsehoods he spewed during the latest debate.
The Nation.(blog)
10. "I told you I would cut taxes for middle-class families, and I did. I told you Id cut taxes for small businesses, and I have." President Barack Obama has made this claim repeatedly during the campaign, but it is not true, as even the liberal Huffington Post acknowledges.
7. "I want to make sure our timekeepers are working here." For the third debate in a row, the Democratic candidate complained that he was not receiving as much time to speak as the Republican. And for the third debate in a row, the Obama/Biden ticket actually spoke for longer--much longer--than the Romney/Ryan ticket,
5. "You can ship jobs overseas and get tax breaks for it." We have heard the same lie for eight years from Obama. In 2004, he ran for U.S. Senate from Illinois on a promise to end such tax breaks. He did it again when he ran for President of the United States in 2008. And yet he has never done anything about it--because there are no such tax breaks.
4. "And the production is up....What youre saying is just not true." Obama contested a claim by Romney that production of oil and gas is down on federal lands. He even accused Romney of not telling the truth. But Romney was right--exactly right, down to the percentage decline.
1. "He did call it an act of terror." The worst untruth told by a moderator in presidential history. Candy Crowley's intervention in favor of Obama caused the president's cheering section to burst into applause, in violation of the rules, and there was little that Romney could say in response. But she was wrong--Obama's reference to "acts of terror" in his Sep. 12 statement was in a general, abstract sense, and came long after he had described the 9/11 attacks on U.S. diplomatic missions as demonstrations against an anti-Islamic video. Even Crowley seemed to realize what she had done: it wasn't long before she walked back her own comment.


text:
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Announcement For more of my art, please visit www.DavidReddickStudio.com!
For more of my art, please visit www.DavidReddickStudio.com!
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Les Vosla on Jan 26, 2014
5 out of 5 stars
Take your chance to get a real piece of comic art here! Well known for his webcomic "Legend of Bill", David Reddick shows off some of his sketches in this booklet. If you otherwise show big comic houses the finger, get some real handiwork for a small price here. It's worth it!
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Susan Bates Regular Cable Stitch Holder, 3-Inch
$36.99 Ships free Australia wideBack to top
Susan Bates Regular Cable Stitch Holder, 3-Inch
by Susan BatesIn Stock
$36.99 Ships free Australia wide
- Cable Stitch holder
- Lightweight aluminum
- Smooth finish
- more info
Delivery: Free shipping anywhere in Australia Delivery within 6-12 working days
(Shipments to NT and rural WA may take longer) Free SMS notifications
(Australian mobile numbers only)
(Shipments to NT and rural WA may take longer) Free SMS notifications
(Australian mobile numbers only)
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Product details:
SUSAN BATES-Regular Cable stitch Holder. This gull cable needle from Susan Bates is made of lightweight aluminum; which has undergone a special anodizing process that etches away all surface impurities. In addition; each cable needle is heat treated for strength and durability and polished for a velvety smooth finish. This cable needle is perfect for working cable designs with worsted weight and finer yarns. This package contains one 3in cable stitch holder. Imported.
- Cable Stitch holder
- Lightweight aluminum
- Smooth finish
Brand: Susan Bates
Product ID: 1117165428858146
Product Dimensions: 12.6cm x 1.3cm x 4cm
- Free delivery Australia wide
- 24/7 parcel tracking
- Customer support
- Full factory warranty
- Easy returns
- Secure checkout
Information above was provided by the manufacturer or local distributor.
Please check the packaging and read instructions prior to using the product.
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Excel Accounting Services
gst submission
With the implementation of GST, everything has been difficult. Rules & regulation & GST tax code are constantly added, company that is updated with the issue will face a high risk from it.
Office politics, highly paid accounting personnel, staff increment & bonuses & inexperience staff is an issue faced.by.most companies.
Beside bookkeeping service, we can also liase with external auditor & GST submission (monthly or quartly) upon request.
Why make yourself headache?
Outsource your account is a solution for it.
We can be contacted at hp no: 010-9643315 or email through [email protected]
Website - None provided
Print this page
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text: What's next for Conrad Black? Add to ... The Globe and Mail Published Monday, Nov. 01, 2010 9:01AM EDT Last updated Monday, Nov. 01, 2010 9:01AM EDT Conrad Black won a minor victory in a U.S. court with two fraud convictions overturned, but a count of obstruction of justice and one other fraud charge were upheld. Black may be retried, or even sent back to prison. Watch More Video: Trump revokes Obama guidelines on transgender bathrooms NDP calls Liberals 'blind' to Trump's approach to asylum seekers Justin Trudeau defends border preclearance bill Sean Spicer: Transgender guidance should be state's right Protesters vow face-off over North Dakota pipeline Floods ravage San Jose area after heavy rains British Muslim teacher forced off U.S.-bound plane North Korean diplomat sought in death of Kim Jong-nam Canada to take in 1,200 mostly Yazidi refugees Trump to spare young immigrants amid ramped up deportation NDP calls on Trudeau to end refugee agreement with U.S. Milo Yiannopoulos resigns from Breitbart amid controversy Muslim group calls for support of anti-Islamophobia motion NYPD chases runaway cow through NYC streets Ralph Goodale calls response to refugees at U.S. border 'magnificent' Refugees rush for U.S.-Canada border Anti-semitic threats are 'horrible': Trump Ottawa police scale icefalls as part of training Africa's newest, rarest crocodile faces battle for survival France's Le Pen refuses to wear headscarf for meeting with Lebanon's grand mufti Comments Share via email Share on facebook Share on twitter Share on LinkedIn Print


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In this article you will find the most popular Micro Four Thirds lenses we choose for recommendation. Want to buy a new lens for your mirrorless system camera, but you can not decide which one to get? Here are some of our choices! As you know the Micro Four Thirds system has a 2x crop factor, soContinue Reading
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Best Lenses for Olympus OM-D E-M1 Mark II Camera
Best lenses for Olympus OM-D E-M1 Mark II camera are listed below for Micro Four Thirds users. Here are the top rated OM-D E-M1 Mark II lenses. Announced back in late, 2016, the E-M1II MFT camera has several improvements over its predecessor. The camera offers a faster processor, higher resolution, better AF and a stabilization system with a 6.5 stops of shake correction. Check this quickContinue Reading
Panasonic updates G85, GX85 and 100-400mm lens firmware
Panasonic has released a new firmware update for its G85, GX85 mirrorless cameras and 100-400mm lens. Firmware Ver.1.2 for G85 and GX85 both reduces the operation noise during the shooting standby or the motion picture recording. Dual I.S.2 function also comes to 100-400mm lens paired with the G85 upgrade. More details about these upgrade can be found below withContinue Reading
Olympus 17mm f/1.2 PRO lens is on the horizon
Olympus is allegedly working on a new 17mm f/1.2 PRO lens which will be announced sometime in 2017. According to latest rumors the company might show new lens prototypes at the CP+ show this February. One of them could be the Olympus 17mm f/1.2 PRO lens. Although the release date and specifications of this lens are not yet known, itContinue Reading
New Subal Housing for Panasonic GX85
Subal announces a new housing for the Panasonic GX85 mirrorless interchangeable lens camera. The new Subal housing for Panasonic GX85 provides access to all camera functions including the ability to open and close the built-in flash. The ergonomic SUBAL design and arrangement of all important elements of the housing allows the camera an easy operation withoutContinue Reading
Olympus E-M1 Mark II review : Best MFT Sensor Yet
Olympus E-M1 Mark II sensor review and test results published by DxOMark. The flagship Micro Four Thirds camera achieved a score of 80 and becomes the best performing MFT sensor yet. The OM-D E-M1's Mark II series achieved a score above both the GX8 and GH4 ratings. As we know this is a newly developed 20.4-MP Live MOS sensorContinue Reading
Panasonic GH5 vs Canon 5D Mark IV Comparison
With the Panasonic GH5 being unveiled in the world of photography, we can think of a tough competition with its competitors in the video segment. So here is a Panasonic GH5 vs Canon 5D Mark IV that shows the highlights to help you for decision. Canon EOS 5D Mark IV features a 30.4 megapixel CMOS sensor with Dual Pixel AF. The CMOS sensor allowsContinue Reading
Panasonic GH5 vs Sony A7SII Comparison
Panasonic has unveiled the GH5 for videographers with amazing features. So here is a Panasonic GH5 vs Sony A7SII comparison that shows the highlights to help you for decision. If you want to have detailed information about the new GH5 impressions first please take a look at this article. The Panasonic GH5 comes with a new 20.3 megapixel sensor without a low-pass filter.Continue Reading
First Panasonic GH5 impressions, tests and videos
The first Panasonic GH5 impressions began to appear on various internet sites with new videos and tests. The device, which is known to have been developed at the Photokina 2016 event, was officially launched for sale last week at CES 2017 event. Featuring a 20.3MP Live MOS image sensor with no optical low pass filter, the PanasonicContinue Reading
Panasonic Announces 12-35mm II, 35-100mm II, 45-200mm II and 100-300mm II Lenses
Panasonic has announced the updated versions of 12-35mm II, 35-100mm II, 45-200mm II and 100-300mm II lenses to have full compatibility with their current camera lineup. All lenses gain a new exterior finish and a new iris for smoother automatic exposure changes, as well as updates to their autofocus system for faster readout. The 12-35 F2.8 IIContinue Reading


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"Dragon's Lair" Strawberry Favorite Tip by Pounder73
Strawberry General: 44 reviews and 44 photos
Favorite thing: Finally no dragons in the picture with me. This is kinda freak'n me out now that I can see these on a bigger screen then on my camera. Lucky they looked like orange lights while camping. I didn't sleep too badly.
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JoAnne: Fair warning. I'm not feeling well and I'm cranky. Enter at your own risk.
Shuk: It's a sunny afternoon and the whole OZ gang takes Mutt for walkies. He breaks loose, and lumbers towards a particularly yummy Professor Plum with a bandaged wrist.
JoAnne: Someone needs to jump on this boy. Right now I don't even care if it's Leo, but he needs some. And I need him to get some.
JoAnne: Does anyone else think his whole timeliness thing is stupid? I mean, sure, if you want to argue that he's doing this because they're a sinking ship and he's trying to turn them into a real business, ok. That even goes along with his earlier intentions, which were only to help them. But IN THE MEANTIME, he only got those extra shares because they insisted, and he DIDN'T want to take over the company and wasn't even thinking about it. So why is he being all Mr. Boss all of a sudden? Especially when it hurts his case with Tao Zi? Why isn't he telling them that wasn't his intention? He doesn't even say it to her parents, who of all people were inclined to at least LISTEN to his story. Frigging writers can't keep their motivations straight.
JoAnne: *nods* He really makes it all sound so reasonable.
Shuk: He even explains while Dork made a brief reappearance. PDLeo looks thoughtful. When the question comes around to the shares situation, he tells them that he sincerely wanted to help OZ Advertising. TaoDad is apoplectic but PDLeo smooths everything down; after all, he was willing to stand there and take the verbal abuse, so he must be genuine.
JoAnne: BUT HE STOPS EXPLAINING AT THIS POINT. Why does he not remind them that they INSISTED on something he NEVER asked for?
Shuk: Chalk Girl asks about Whiny, and Sexy truthfully says she's is okay for now but has an uncertain future. Once he leaves Tao House, he receives a phone call from Foster Mom. It seems Whiny can't wipe her butt without Sexy in the hospital room.
JoAnne: I care so little that I broke the grasshopper's tiny violin and threw it away. I won't even let him play the world's tiniest violin for her! No!
JoAnne: Slower, at the very least.
Shuk: Sexy makes small talk with the two women. Whiney promises to work hard with her physical therapist, as long as Tian Xing is there every day. Blah blah clingy vine blah blah.
JoAnne: Stop talking with that fucking baby voice.
JoAnne: Might as well. It's not like anyone is 'leaving Taiwan.'
Shuk: Before he can escape, Toady asks about the completion bond money. In a roundabout way, he gets Sexy to agree that Toady can review OZ's operation and assignments. What does he have up his sleeve?
JoAnne: So he did use company funds? The fucking idiot. Lance has exactly what you'd expect up his sleeve, and Xian Ting has now seriously diminished whatever affection I still held for him in this freaking nightmare.
Shuk: Sexy grabs Toady Jr and Helen to pull them off exclusively for OZ, telling them to not stay puppets to TX. FosterMom is surprised by this; Lance fires back and tells Sexy to make sure to stop by the hospital to keep Huan Huan from being upset.
JoAnne: Is that the plan now? Any time Xian Ting does something, Lance will just fire back with 'yeah...well....MY SISTER!' People need to die.
Shuk: At OZ, everyone is studiously ignoring work and ignoring Sexy until he's forced to play hardass. At the conference table, he tells everyone to continue working on their current project. When the TX guys show up, Bangs and Kitty seem happy. Sexy continues around the table. Chalk Girl takes the place of Dork and is now the creative head; PDLeo is in charge of all filming and everyone else stays the same.
JoAnne: And THESE idiots: Jesus take the wheel. PLEASE. 1) Your company is this little rinky dink operation that got what it got because of Xian Ting in the first place. 2) Ain't nobody got time to be all take-overish about such a nothing place. And even if they DID...3)who takes over a company that has nothing, really, but these 5 employees...and then fires the employees? If I were Tian Xing I'd be so irritated by your childish behavior that I might just shut you down for being ASSHOLES.
Shuk: The TX team passes around snacks from the contracted company. Sexy challenges them to come up with an ad campaign that surpasses what her brother previously did for the same company. And since everyone thinks he's a bad guy, Tian Xing will recuse himself from anything regarding the project. That way, the company lives or dies on their own merit, just like before he got involved. Sexy exits, stage left.
JoAnne: Not exactly completely out of it. Because you know if they failed, they'd still keep plugging along, pretending to be an actual business. But he'll shut them down if they fail, probably. Unless you think that was an empty threat, when he said he'd decide after?
JoAnne: And I say nothing either, because I couldn't give a rat's ass about any of them.*
|JoAnne's favorite shirt to wear while watching this episode.
JoAnne: *
Shuk: Sexy chases Chalk Girl out to the Mystery Machine, and chastises her for leaving during office house and ignoring the new GM. She bites back that she plans to visit Whiney, and drives off over his offer for them to go together.
JoAnne: This boss thing is certainly irritating. Although I admit at this point that I hate everyone at Oz so much that it's a little fun to see Xian Ting be so frustrated that he just acts like a dick all the time. They don't really deserve different.
JoAnne: You have been very patient because her voice was plucking my LAST nerve the first time we ever met her.
JoAnne: That blankness mirrors the gaping hole of the future she imagines for Whiney. It's really powerful stuff. I totally felt nothing. See? See how powerful that is? She has me FEELING like the blankness of Whiney's body. AMAZING.
Shuk: OZTX folks are playing video games together when Sexy and Chalky arrive back at the office with box lunches. They start a brainstorming session. At the end of the day, PDLeo walks her home, commenting that she seems more at ease over the last couple of days, and she admits she is making a concerted effort to be positive.
JoAnne: They only put that part in there so we'd understand what was happening because otherwise, we'd get no clues from her behavior.
JoAnne: Par for the course. She's actually kind of a bitch, when you get down to it.
Shuk: It's just Lance and Huan Huan at the hospital. Whiny wonders how things are between Sexy and Chalky. Lance believes that, since she is injured, she is Xian Ting's top priority. Lance comes up with a brilliant evil scheme: if his sister stays injured, then Tian Xing won't ever leave her side. WTF???
JoAnne: I cannot repeat what I said at this point, mostly because I can't remember it. But it was complicated and long and really, really, really insulting.
Shuk: Whiny is playing wheelchair ball in the hospital park when Sexy shows up. He starts to massage her legs, which twitch when he touches them. He's excited – is the feeling coming back? She lies and says no. Lance nails the final link in Sexy's chains by showing him a forged letter from the doctor stating Huan Huan will never walk again.
JoAnne: Oh, can we please send someone to jail? Please? But does this mean they're lying to her mother, too? Is she just supposed to do this forever? It can't last long, it's too stupid of a plan. Won't the doctors just flat out know she's faking?
Shuk: Tian Xing goes for some alone time in the stairwell, ultimately screaming out his pain and sadness, before regaining his composure, if not his equilibrium.
Shuk: Butler Fu meets up with Tao Zi to plug his young master's virtues and plead for them. He also describes Dork as the kindest and best part of Tian Xing, as well has his wish to make OZ stronger, not to destroy it. She interrupts him; all that may be true, but she still can no longer trust him.
JoAnne: Why? Why? WHY? If you know that these things are true and you know why it was done and how it happened and that the intent was never malicious, what is there not to trust? That he might high-handedly make decisions without involving you in them? Well THAT'S certainly reason enough to despise someone, yes, of course. NO, you idiot. No it's not. And I kinda think he has learned his lesson, anyway. But then again, he is playing Boss Mr. Jerk right now for some reason.
JoAnne: I expect to wake up tomorrow wearing a size 10. Is that all it takes?
Shuk: It's late late at OZ, and Chalk Girl has a stretch at her desk. She touches the bracelet still on her wrist and remembers its installation and the kiss afterward. At the same time, Sexy is still at DorkHouse, looking at the warehouse selfie he took of the two of them, and flashes back to several of their hugs.
Shuk: Time for the new ad campaign! Sexy shows up outside OZ and spots Chalky reading her ideas out loud. Clearly she's having a hard time being creative. (Because she has no talent or training for this job. Why won't people just admit it?) He catches up with her by the park bench, and begins to tell her something, but after several tries, he falls back to asking about the advertisement contract.
JoAnne: I'm sure she's comforted by her logic, but she's wrong. And not logical at all.
Shuk: She hurries away, leaving Sexy standing there frustrated. A bicyclist rides by and knocks her down. Tian Xing immediately rushes over and bandages her knee. She stares at his face while he focuses on covering the bleed.
JoAnne: I am seriously concerned for Korea and Taiwan. It seems every time you turn around, people are walking into each other or riding into each other, always resulting in at least one person hitting the ground hard enough to draw blood. Do they not look where they are going? Is it an issue of depth perception? Do they have any? Is it the prevalence of eye surgeries that is affecting their ability to see properly? Are they warned about this when they agree to the operation?
Shuk: Sexy brings in the mugs as they take a short break. He gets a postie pad off Chalky's desk and starts to write something. When a discouraged Tao Zi returns to her desk she finds the postie under her coffee mug with two sonograms: "Fulfilling Dreams." She smiles as an idea materializes, but it fades when she realizes where it came from. He's reading a magazine while he sips his beverage, completely ignoring her.
JoAnne: I thought here that he was really just better at verbalizing clearly what she had been stumbling around, rather than planting an idea in her head - did you see it that way?
Shuk: She restarts the meeting, and this time he sits in on it. We find out that, after her brother's work, Lu Tian Xing came up with the next successful advertising campaign for the company. The concept literally gels into existence with everyone's input. The idea includes a documentary-style operation involving kids at a local children's hospital. Sexy stands up and compliments them for their creativity before leaving. Guess what?? PDLeo looks thoughtful.
JoAnne: I'm shocked.
JoAnne: She's already feeling him. Maybe not so dumb after all.
Shuk: He was taking her to physical therapy. When Whiny sees him not paying attention to her, she fakes a fall. So she jeopardizes her recovery for someone who will never love her the way she wants. Wow.
JoAnne: But wait, it's the recovery that she's denying anyway, so if it goes away for real, isn't that a plus for her? I will smother her with a pillow.
Shuk: While wandering around the grounds, Tao Zi sees a little girl sitting with a poster. She tries to see what the girl wrote, but only succeeds in making the girl run away.
JoAnne: Because I have nothing to say about this, I will mention that I think I learned that Puff and Tia are in the same girl group? Dream Girls? This I did not know, and am now consumed by uncomfortable thoughts of them comparing Aaron backstage before concerts.
Shuk: For the second time, Tian Xing and Huan Huan bump into Tao Zi and Leo, but this time they stop. Lance and FosterMom show up at the same time. Mom is gracious over Chalk Girl's apology, and finds out the faked-out paraplegia diagnosis. (See, bullshit. Why would she just be finding out what's going on with her own child? Stupid writer.) Whiny looks upset, but Chalk Girl can't see her for locking eyes on the hot stare of our SexyAdGuyDork. Lance says it out loud; Huan Huan may spend the rest of her life in a wheelchair.
JoAnne: Finish the sentence, Lance: ..because she threw herself down a hill. Now everyone, look at Huan Huan and say this: What did you THINK would happen, idiot? You made your bed, now lie in it. Alone.'
Shuk: Chalk Girl bolts; when she stops, she remembers that Little Brat pried herself loose from Sexy's grip. PDLeo catches up to her as she has a guilt meltdown; he shoulders some of the blame, since he didn't out Dork before she fell in love with him, and since he never confessed his own love to her.
JoAnne: Fine, everyone, blame Leo for Huan Huan's injury. Let HIM take care of her forever, while the other two go off and have a happy life.
Shuk: She falls back to Blank Expression # 63 as Leo continues: He was willing to stand back and be the big brother for her happiness, but now he plans to protect her, make her smile, and love her as a man. Not much reaction on her part.
JoAnne: She's shocked at the thought of Leo having man parts. As are we.
JoAnne: Leo, go try to make love to the office. Then tell me it doesn't matter which.
Shuk: Lu Tian Xing responds: whether the company or the girl, he plans on acting with sincerity to renew everyone's trust. And now the competition really begins.
JoAnne: So all the beforehand was just preliminaries? Kill me. Kill me now.
Shuk: Things are moving along in predictable patterns. You can already see that Whiny is feeling the pressure of keeping secrets. Tian Xing is much more relaxed and confident, but then again, he's shed his secrets and can be open about anything. Leo's posturing doesn't sway me, since he plans to chase his love in "his own way" which means thoughtful stares of inaction.
JoAnne: Don't forget the gentle forehead flicking. That's key, there.
JoAnne: Quite frankly, Oz is not a going concern and never will be with Tao Zi at the helm. Shut it down or absorb it into the larger company.
JoAnne: And I'm guessing that unless they manufacture some OTHER big issue to deal with before the big issue we all know is coming, we're actually more like 2/3 or 3/4 done. Isn't it fun how they don't announce how long a show will be, though?
|Run, Tian /Xing! Don't let Clingy get you!!!


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Animation poses
This project received 21 bids from talented freelancers with an average bid price of $11 USD / hour.Get free quotes for a project like this
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Project Description
I have a 3d animated character that I need recreated in different poses. I will provide the raw files and a series of photos of myself in the poses that I want recreated. I would like to have about 60 different poses created. The files I have are complete and edit ready. I just need the little character modelled into different positions.
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text: We came here on a recommendation from the hotel we were staying at , we also received a discount voucher by booking through the hotel ( Ramada Encore ) . We have been fortunate to have traveled around the UK and Australia extensively and had never been to a Greek Restaurant ! On arrival staff were friendly and showed us... More


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Days Inn Daytona Beach Speedway
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There are several eateries close by including Wing House or Ale House, both walking distance from our hotel. Grab a quick bite at McDonald's or have dinner at Red Lobster, one-half mile from our hotel. Olive Garden and Outback Steakhouse are less than three miles away and Miller's Ale House and Thai Cuisine are also nearby our hotel.
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Jubilee Campground is a 2.6 mile heavily trafficked loop trail located near Elgin, Oregon that features a lake and is good for all skill levels. The trail offers a number of activity options and is best used from June until September. Dogs are also able to use this trail.
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buying the business? Can this partner who is trying to get out get the courts to somehow disolve this partnership?
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Norton, Worcestershire WR5 2PT
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Affluent village locationNet T/O £501,851 year ended March 2015Trade split 50% food/ 50% WetLounge/bar and...More Details
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WORCESTERSHIRE - FAMED RIVERSIDE INN Two section main bar. Restaurant (90). Function suite (100). Nine en s...More Details


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Everyone needs children room design ideas and wants the best for their child. There's nothing better for a little princess than living in her magical pink world. Create a lovely enchanting realm for your baby girl and give her the feeling of softness and sweetness that she deserves. Girls love fairytales and magic, a lovely pink interior will give them the comfort and freedom to create their own magical world. It will develop their imagination and creativity.
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Nautical Nightmares - Twilight Halloween Sail
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Nautical Nightmares - Twilight Halloween Sail
Sun, October 29, 2017, 3:45 PM – 6:30 PM PDT
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Join the captain and crew of the traditional schooner FREDA B for a special Halloween Sail all about the Ghosts, the Legends and the Lore of the Bay Area. Set sail to catch the sunset and twilight hour on the bay. Learn about bootleg gangsters like Baby Face Nelson, and Sausalito's Madam, Madam Mayor Sally Stanford and their rise and fall on our local lands. Discuss the many shipwrecks and things that go bump in the night.
Prize for Scariest Nautical Costume!
Boarding: 3:45pm
Departure: 4:00pm
Return: 6:30 pm
On-deck Cash Bar- Cash ONLY we do not accept credit cards on this traditional girl.
Sonoma and Napa Valley wines by the glass $10-$12
California Craft Beers by the bottle $5
Premium pop and sparkling water $4
French Press Organic Taylor Maid Coffee, Hot Chocolate, Hot Apple Cider and Tea $5
Irish Coffee $12
Clam Chowder with SF Sourdough: $12 a mug
~No outside beverages are allowed on board~
Trick or Treat!!!
Beverages and Snacks:
CASH BAR - Fresh housemade Organic French Press Coffee, Hot Chocolate with whipped cream, Mimosas, California Craft Beer and Sonoma/Napa Valley Wines are available for CASH purchase on deck. Please note: No outside beverages or credit cards are accepted. Absolutely no outside beverages allowed.
What to Wear:
Dress in layers, sailing on the San Francisco Bay offers everchanging views, and exciting microclimates. Weather can change in a minute. Windbreaker, warm base layer, gloves, hat, scarf, sunglasses, and comfortable shoes are encouraged. Don't forget your sunscreen! NO HIGH HEELS.
Please arrive early to find parking and the boat.
Parking is located in one of the MUNICIPAL LOTS located around the Sausalito Yacht Harbor. Parking costs between $1 and $3 per hour. Freda B sails on time. There are NO REFUNDS for guests who miss the boat. NO outside beverages or dogs are allowed on board. Walk to 100 Bay Street in Sausalito and you will be at the head of our pier. Freda B is located at the Sausalito Yacht Harbor, Slip 907, Sausalito, CA 94965
Sailing on the San Francisco Bay is weather dependent. We sail in most weather, including cold, wind, fog,drizzle and light showers. On occasion, we will need to reschedule a sail due to extreme wind or rainy weather. If this is necessary, you will be notified within 24 hours of scheduled sail. If we cancel due to weather, you will be offered to reschedule. Our Captains monitor the most sophisticated weather channels and make every effort to bring you information in the timeliest manner. We appologize in advance if the weather complicates any special occasion plans.
A ticket is required for all passengers, including babes in arms. Children 14 and under must be accompanied and supervised at all times by an adult.
SF Bay Adventures does offer a group discount for regularly scheduled public sails for groups of 6 or more. Please contact the ticket desk at firstname.lastname@example.com for more information.
Large group? Schooner Freda B is available for private charters for up to 49 guests. Please contact firstname.lastname@example.com to book the entire boat!
Due to the popularity of this sail we do not offer guests an option to cancel or reschedule within 7 days of the sail. If you need to cancel please do so at least 1 week in advance or for extreme emergency situations within the week of sail, please contact the ticket desk with your reason at email@example.com.
Local Restaurants:
Before boarding or after we return, dine at one of Sausalito's many delicious restaurants walking distance to the boat:
We look forward to welcoming you aboard!!!
The forecast look good, but this is a weather dependent event. If we need to cancel you will be refunded.
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