Pyridine → n-((1s,2r)-2-{[(Cyanomethyl)amino]carbonyl}cyclohexyl)-4-{[(pyridin-4-ylmethyl)amino]sulfonyl}benzamide

Participants

Reaction Steps

To a solution of 912 mg (5.03 mmol) (1R,2S)-2-amino-N-(cyanomethyl)cyclohexanecarboxamide (prepared according to method C) and 895 uL (11.07 mmol) pyridine dissolved in 10 mL dichloromethane was added 1.12 g (5.03 mmol) 4-(fluorosulfonyl)benzoyl chloride. The mixture was stirred for 30 minutes, partitioned between dichloromethane and 1 N HCl, dried over magnesium sulfate and concentrated to provide 1.54 g (84% yield) of crude product, pure by 1H NMR. To a mixture of 100 mg (0.272 mmol) of the above crude N-((1S,2R)-2-{[(cyanomethyl)amino]carbonyl}cyclohexyl)-4fluorobenzamide and 114 uL (0.817 mmol) triethylamine dissolved in 5 mL dichloromethane was added 88 mg (0.817 mmol) 4-picolylamine. The mixture was stirred at room temperature for 3 days, partitioned between ethyl acetate and water, dried over magnesium sulfate and concentrated. Column -chromatography, eluting with 20:1 dichloromethane:methanol provided 59 mg (48% yield) of N-((1S,2R)-2-{[(cyanomethyl)amino]carbonyl}cyclohexyl)-4-{[(pyridin-4-ylmethyl)amino]sulfonyl}benzamide, which was used in the preparation of compound 58 of Table 1.

Provenance & Evidence