反应详情

温度

60 °C

To a solution of 2-(1-tert-butoxycarbonyl-1H-thieno[3,2-c]pyrazol-3-yl)-5-(hydroxy-phenyl-methyl)-indole-1-carboxylic acid tert-butyl ester [640 mg, 1.17 mmol, Intermediate (12)] in Dichloromethane (25 mL) is added Dess-Martin Periodinane (677 mg, 1.69 mmol) and stirred at room temperature. After 30 minutes water (5 mL) is added and stirred for 10 minutes. The reaction mixture is diluted with dichloromethane (50 mL) and washed twice with a mixture of 10% Na2S2O3/saturated NaHCO3 (5 mL), NaHCO3 (10 mL), water (10 mL), brine and dried over sodium sulfate. The residue is chromatographed on 35 g silica gel cartridge, eluting with 30% ethyl acetate/Heptane to afford 5-benzoyl-2-(1-tert-butoxycarbonyl-1H-thieno[3,2-c]pyrazol-3-yl)-indole-1-carboxylic acid tert-butyl ester [440 mg, 69%, Intermediate (13)] as a white solid; LC/MS: 544 (M+H). Step 2. A mixture of 5-benzoyl-2-(1-tert-butoxycarbonyl-1H-thieno[3,2-c]pyrazol-3-yl)-indole-1-carboxylic acid tert-butyl ester [122 mg, 0.224 mmol, Intermediate (13)] in tetrahydrofuran (9 mL) and 1M KOH(aqueous, 2 mL) is heated at 60° C. oil bath overnight. The solvent is removed and added water (5 mL). The water layer is neutralized with 3N hydrochloric acid and extracted three times with ethyl acetate (20 mL). The combined ethyl acetate phases are washed with brine and dried over sodium sulfate. The residue is chromatographed on 10 g silica gel cartridge, eluting with 50 to 100% ethyl acetate gradient in heptane to afford phenyl-[2-(1H-thieno[3,2-c]pyrazol-3-yl)-1H-indol-5-yl]-methanone (58 mg, 75%, Example 25) as a pale yellow solid; 1H NMR [(CD3)2SO)]: δ 13.38 (1H, s), 12.09 (1H, s), 8.05 (1H), 7.78 (8H, m), 7.23 (1H, d, J=5.2 Hz), 6.87 (1H); LC/MS: 344 (M+H).

1. customThe solvent is removed
2. additionadded water (5 mL)
3. extractionextracted three times with ethyl acetate (20 mL)
4. washThe combined ethyl acetate phases are washed with brine
5. dry with materialdried over sodium sulfate
6. customThe residue is chromatographed on 10 g silica gel cartridge
7. washeluting with 50 to 100% ethyl acetate gradient in heptane