For "proof-of-concept", we set out to synthesise initially two heterotrivalent compounds, MN666 and MN675 (2) (Figure ). The structure of 1 shares a scaffold much like that of SIM1, differing only by a JQ1 ligand being substituted by thalidomide via an aniline tether. 2 is a smaller analogue of 1, with a PEG unit removed from both VH032-JQ1 and VH032-thalidomide sides to the linker. Using a similar route described by for the synthesis of SIM1, 11 alcohol 3 was first alkylated with allyl bromide in a solution of potassium hydroxide and tetrabutylammonium bromide in toluene and water to give allyl ether 4 (Scheme 1). The acetonide of 3 was hydrolysed with trifluoroacetic acid (TFA) in methanol and water to yield diol 5. Next, diol 5 was di-deprotonated using 4 equivalents of sodium hydride at 0°C in dimethylformamide (DMF), before the addition of azido mesylates 6 and 7 and heating to 60°C to yield dialkylated allyl ethers 8 and 9, respectively. Next, alkenes 8 and 9 were oxidatively cleaved with sodium periodate, 2,6-lutidine and a catalytic amount of osmium tetroxide in dioxane and water to yield aldehydes 10 and 11. Then, aldehydes 10 and 11 underwent a Pinnick oxidation by treating them with 2-methyl-2-butene, monobasic sodium phosphate and sodium chlorite in tert-butanol and water to yield carboxylic acids 12 and 13 (Scheme 1).