Water → {4-[(1H-indole-6-carbonyl)-amino]-phenyl}-acetic acid tert-butyl ester

HRID 1715832

반응식

HRID 1715832 반응식
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:10]([OH:12])=O)[CH:8]=2)[CH:3]=[CH:2]1.CN1CCOCC1.[C:20]([O:24][C:25](=[O:34])[CH2:26][C:27]1[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][CH:28]=1)([CH3:23])([CH3:22])[CH3:21].O>CN(C)C=O>[C:20]([O:24][C:25](=[O:34])[CH2:26][C:27]1[CH:28]=[CH:29][C:30]([NH:33][C:10]([C:7]2[CH:8]=[C:9]3[C:4]([CH:3]=[CH:2][NH:1]3)=[CH:5][CH:6]=2)=[O:12])=[CH:31][CH:32]=1)([CH3:23])([CH3:21])[CH3:22]

참가 물질

6

반응물 4

HCID 962WaterHCID 79724-MethylmorpholineHCID 5952301H-indole-6-carboxylic acidHCID 2760930Tert-butyl 2-(4-aminophenyl)acetate

생성물 1

HCID 68434833{4-[(1H-indole-6-carbonyl)-amino]-phenyl}-acetic acid tert-butyl ester수율 11.7%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

반응 조건

온도
60 °C

실험 절차

A solution of indole-6-carboxylic acid (2.00 g, 12.40 mmol) in dimethylformamide (20.00 mL) under argon was treated with N-methyl morpholine (6.82 mL, 62.04 mmol), O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium-hexaflurophophate (HATU) (7.08 g, 18.62 mmol) and (4-amino-phenyl)-acetic acid tert-butyl ester (2.57 g, 12.40 mmol). The mixture was warmed at 60° C. and stirred for 18 hours. After cooling to room temperature, water (15.00 mL) was added. The resulting slurry was extracted with ethyl acetate and the combined organic phases washed with brine, dried over magnesium sulphate and evaporated. The residue was purified by flash chromatography (heptane/ethyl acetate gradient), to yield pure {4-[(1H-indole-6-carbonyl)-amino]-phenyl}-acetic acid tert-butyl ester (0.51 g) and a mixture of {4-[(1H-indole-6-carbonyl)-amino]-phenyl}-acetic acid tert-butyl ester and 1H-indole-6-carboxylic acid [1,2,3]triazolo[4,5-b]pyridin-3-yl ester (3.41 g). This was dissolved in tetrahydrofuran (34.00 mL) and treated with 1N NaOH. The mixture was stirred at room temperature for 4 hours, then extracted with ethyl acetate. The combined organic phases were washed with brine, dried over magnesium sulphate and evaporated, and the residue triturated in ether to afford {4-[(1H-indole-6-carbonyl)-amino]-phenyl}-acetic acid tert-butyl ester (1.36 g), which was combined with the aliquot obtained by flash chromatography. Total yield of {4-[(1H-indole-6-carbonyl)-amino]-phenyl}-acetic acid tert-butyl ester, 1.87 g (43%), MS (mass spectrometry) (ISP): m/e=351.3 (M+H). As used herein (M+H)=the molecular weight of the compound plus a proton.

후처리

  1. temperatureAfter cooling to room temperature
  2. extractionThe resulting slurry was extracted with ethyl acetate
  3. washthe combined organic phases washed with brine
  4. dry with materialdried over magnesium sulphate
  5. customevaporated
  6. customThe residue was purified by flash chromatography (heptane/ethyl acetate gradient)

출처 및 근거

ORD 기록
ord-5f27f30636b540eb9f018409819a6869
출처 데이터셋
uspto-grants-2010_09
특허 번호
US07799933B2

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