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

HRID 1715832

反応式

HRID 1715832 の反応式
[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]

参加物

6

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
60 °C

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-5f27f30636b540eb9f018409819a6869
出典データセット
uspto-grants-2010_09
特許番号
US07799933B2

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