反应详情

A mixture of 5-(5-(3-fluoro-4-hydroxyphenyl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-7-yl)-3-(trifluoromethyl)picolinonitrile (Example 1, 100 mg, 0.23 mmol), benzyl alcohol (35 μL, 0.30 mmol) triphenylphosphine (79 mg, 0.30 mmol), and diisopropyl azodicarboxylate (60 μL, 0.30 mmol) in THF (5 mL) was stirred at room temperature for 2 days then heated to 60° C. overnight. The reaction mixture was absorbed on silica gel and purified by column chromatography on silica gel eluting with 0 to 50% EtOAc/Hexanes to afford impure desired product. The solid was triturated in MeOH, filtered, and dried to afford 36 mg of 5-(5-(4-(benzyloxy)-3-fluorophenyl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-7-yl)-3-(trifluoromethyl)picolinonitrile as a white solid. 1H NMR (300 MHz, DMSO-d6) δ 9.21 (d, 1H), 8.75 (d, 1H), 7.53-7.36 (m, 7H), 7.23 (d, 1H), 5.28 (s, 2H), 2.66-2.60 (m, 2H), 2.53-2.43 (m, 2H), 2.02-1.92 (m, 1H), 1.61-1.55 (m, 1H).

1. temperaturethen heated to 60° C. overnight
2. customThe reaction mixture was absorbed on silica gel
3. custompurified by column chromatography on silica gel eluting with 0 to 50% EtOAc/Hexanes