5-benzoyl-2-(1-tert-butoxycarbonyl-1H-thieno[3,2-c]pyrazol-3-yl)-indole-1-carboxylic acid tert-butyl ester → phenyl-[2-(1H-thieno[3,2-c]pyrazol-3-yl)-1H-indol-5-yl]-methanone

HRID 2111171노트

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HRID 2111171 반응식
C(OC([N:8]1[C:16]2[C:11](=[CH:12][C:13]([C:17](=[O:24])[C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[CH:14][CH:15]=2)[CH:10]=[C:9]1[C:25]1[C:26]2[S:39][CH:38]=[CH:37][C:27]=2[N:28](C(OC(C)(C)C)=O)[N:29]=1)=O)(C)(C)C>O1CCCC1.[OH-].[K+]>[C:18]1([C:17]([C:13]2[CH:12]=[C:11]3[C:16](=[CH:15][CH:14]=2)[NH:8][C:9]([C:25]2[C:26]4[S:39][CH:38]=[CH:37][C:27]=4[NH:28][N:29]=2)=[CH:10]3)=[O:24])[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1

참가 물질

4

반응물 1

HCID 576374025-benzoyl-2-(1-tert-butoxycarbonyl-1H-thieno[3,2-c]pyrazol-3-yl)-indole-1-carboxylic acid tert-butyl ester2회

생성물 1

HCID 135489135phenyl-[2-(1H-thieno[3,2-c]pyrazol-3-yl)-1H-indol-5-yl]-methanone수율 75.4%

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매HCID 14797Potassium Hydroxide용매

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온도
60 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-e658dfc0e0ef4fa9848bcc3f38008c1e
출처 데이터셋
uspto-grants-2009_04
특허 번호
US07518000B2

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