Sodium Hydroxide → Sodium 3-(N-(4-(4-(azetidine-1-carbonyl)pyridin-2-yloxy)cyclohexyl)-4-methylcyclohexanecarboxamido)-5-(3,3-dimethylbut-1-ynyl)thiophene-2-carboxylate

Participants

Reaction Steps

NaH (60 mg of a 60% oil dispersion, 1.50 mmol) was added in portions to a solution of 5-(3,3-dimethyl-but-1-ynyl)-3-[(4-hydroxy-cyclohexyl)-(4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid (130 mg, 0.291 mmol) and azetidin-1-yl-(2-chloro-pyridin-4-yl)-methanone from the previous step (290 mg, 1.47 mmol) in DMF (3.0 mL) at 0° C. After 30 min the reaction was warmed to room temperature and then heated at 85° C. for 3.5 h. The reaction was cooled, aqueous NaOH (0.5 mL of a 1.0 N solution) was added and the reaction evaporated to dryness to give a solid residue. The solid was purified by column chromatography on reverse phase C18 silica gel (100% water to 20% acetonitrile/water). Fractions containing product were pooled and lyophilized to give the desired product as a colorless solid (140 mg, 77%). HPLC retention time: 6.41 min (2-98% acetonitrile:water with 0.05% trifluoroacetic acid).

Provenance & Evidence