反应详情

To a solution of 4-[[3,3-difluoro-3-(4-fluorophenyl)-propyl]sulfanyl]-2-methyl-thiazole-5-carboxylic acid (0.25 g, 0.72 mmol) in DMF (4 ml) are added O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (347 mg, 1.08 mmol) and N-methylmorpholine (0.16 ml, 1.44 mmol) at 0° C. followed by the addition of 4-fluorobenzyl amine (0.01 ml, 0.86 mmol). The reaction mixture is stirred at RT for 3 h. After completion of the reaction, the mixture is poured onto ice-water, extracted with EtOAc (3×15 ml). The combined organic layers are washed with brine (20 ml), dried over sodium sulfate and evaporated to dryness to yield the crude product, which is purified by column chromatography (silica gel, 5% acetone/hexane) followed by preparative HPLC affording 4-[[3,3-difluoro-3-(4-fluorophenyl)-propyl]sulfanyl]-N-[(4-fluorophenyl)-methyl]-2-methyl-thiazole-5-carboxylic acid amide (example 15) (0.2 g, 0.42 mmol, 36%). [M+H]+ 455.1.

1. customAfter completion of the reaction
2. additionthe mixture is poured onto ice-water
3. extractionextracted with EtOAc (3×15 ml)
4. washThe combined organic layers are washed with brine (20 ml)
5. dry with materialdried over sodium sulfate
6. customevaporated to dryness
7. customto yield the crude product, which
8. customis purified by column chromatography (silica gel, 5% acetone/hexane)