(S)-(4-(3,4-Dichlorobenzyl)morpholin-2-YL)methanamine → N-[[(2S)-4-[(3,4-dichlorophenyl)methyl]morpholin-2-yl]methyl]-2-(5-methyl-2-pyridin-3-yl-1,3-oxazol-4-yl)acetamide;formic acid

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Reaction Conditions

Reaction Steps

N,N′-carbonyldiimidazole (15 mg) was added to a stirred solution of Intermediate 34 (20 mg) at 22° C. under nitrogen, and the mixture was stirred at 22° C. for 1 h. Intermediate 9 (26 mg) was added and the mixture stirred at 22° C. for 24 h. The mixture was applied directly to a sulphonic acid ion exchange cartridge (Isolute SCX, 2 g) and eluted with methanol followed by 10% 0.880 ammonia in methanol. Evaporation of the methanolic ammonia fraction gave a gum (50 mg) which was further purified by solid phase extraction on silica gel (1 g Varian Bondelut cartridge), eluting with chloroform, ether, ethyl acetate, acetone and methanol to give a gum (38 mg). The gum was partitioned between dichloromethane and water, and the organic layer treated with polystyrene methylisocyanate resin (Argonaut, 95 mg, 1.6 mmol/g). After shaking for 4 h the resin was filtered off and the filtrate evaporated to give a gum (29 mg), which was further purified by chromatography on silica gel, eluting with dichloromethane:ethanol:0.880 ammonia 100:0:0-95:5:0.5, followed by mass directed preparative HPLC to give the title compound (7.6 mg).

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