Sodium hydride → {(3S,4R)-4-(3,4-Dichloro-phenyl)-1-[1-(1-methyl-cyclopropanecarbonyl)-piperidine-4-carbonyl]-pyrrolidin-3-yl}-methyl-carbamic acid 2-fluoro-pyridin-3-yl ester

関与物質

反応条件

反応手順

A mixture of 50 mg (0.11 mmol) [(3R,4S)-3-(3,4-Dichloro-phenyl)-4-methylamino-pyrrolidin-1-yl]-[1-(1-methyl-cyclopropanecarbonyl)-piperidin-4-yl]-methanone, 16.2 mg (0.12 mmol) DIPEA and 11.8 mg (0.04 mmol) triphosgene in 5 mL THF at −78° C. was allowed to come to 0-5° C. during 2 h, concentrated under vacuum and dissolved in 1 mL DMF. A solution of 65.5 mg (0.57 mmol) 2-fluoropyridine-3-ol in 1 mL DMF was treated with 18.2 mg (0.45 mmol) NaH 55% in mineral oil and heated to 45° C. for 1 h. This solution was added to the activated amine in DMF and the mixture was shaken for 90 minutes at 80° C. The mixture was filtered and the filtrate was subjected to preparative HPLC on reversed phase eluting with a gradient formed from acetonitrile, water and NEt3. The product containing fractions were evaporated to yield 42 mg (64%) of the title compound as off-white foam. MS m/e: 577.3 [M+H]+.

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