Phenylacetyl chloride → {1-Cyclohexyl-2-[6-(6-fluoro-1H-indol-3-yl)-4-phenylacetyl-hexahydro-pyrrolo[3,2-b]pyrrol-1-yl]-2-oxo-ethyl}-carbamic acid tert-butyl ester

HRID 1949638ノート

反応式

HRID 1949638 の反応式
C[O:2][C:3]([N:5]1[CH2:9][CH:8]([C:10]2[C:18]3[C:13](=[CH:14][C:15]([F:19])=[CH:16][CH:17]=3)[NH:12][CH:11]=2)[CH:7]2[N:20]([C:23](=[O:39])[CH:24]([NH:31][C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH:25]3[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]3)[CH2:21][CH2:22][CH:6]12)=O.[C:40]1([CH2:46]C(Cl)=O)[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1>C(Cl)Cl>[C:35]([O:34][C:32](=[O:33])[NH:31][CH:24]([CH:25]1[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]1)[C:23]([N:20]1[CH2:21][CH2:22][CH:6]2[N:5]([C:3](=[O:2])[CH2:46][C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)[CH2:9][CH:8]([C:10]3[C:18]4[C:13](=[CH:14][C:15]([F:19])=[CH:16][CH:17]=4)[NH:12][CH:11]=3)[CH:7]12)=[O:39])([CH3:38])([CH3:37])[CH3:36]

参加物

4

反応物 2

HCID 7679Phenylacetyl chlorideHCID 674097574-(2-tert-Butoxycarbonylamino-2-cyclohexyl-acetyl)-3-(6-fluoro-1H-indol-3-yl)-hexahydro-pyrrolo[3,2-b]pyrrole-1-carboxylic acid methyl ester

生成物 1

HCID 67408591{1-Cyclohexyl-2-[6-(6-fluoro-1H-indol-3-yl)-4-phenylacetyl-hexahydro-pyrrolo[3,2-b]pyrrol-1-yl]-2-oxo-ethyl}-carbamic acid tert-butyl ester収率 66.4%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

反応条件

温度
0 °C

実験手順

A solution containing amine 50 (296 mg, 0.61 mmol) in DCM (8 mL) was cooled to 0° C. TEA (145 mg, 1.43 mmol) was added followed by phenylacetyl chloride (105 mg, 0.68 mmol) and the reaction mixture was warmed to ambient temperature. After 40 min, the reaction mixture was diluted with DCM and the resulting organic solution was washed successively with 1M HCl and brine, dried over anhydrous Na2SO4, filtered, and concentrated. The crude product was purified by flash silica gel chromatography (1:1 hexanes/EtOAc to 1:2 hexanes/EtOAc) to afford 244 mg (66%) of 56 as an off-white-colored foam. 1H NMR (300 MHz, CDCl3), mixture of amide rotamers: δ8.27 (s, 0.7H), 8.20 (s, 0.3H), 8.02 (dd, J=5.1, 8.4 Hz, 0.7H), 7.35-7.27 (m, 5H), 6.96-6.89 (m, 2H), 6.53 (s, 0.3H), 6.14 (s, 0.7H), 5.34 (d, J=9.3 Hz, 0.7H), 4.77 (d, J=5.1 Hz, 0.3H), 4.51-4.38 (m, 2H), 4.34-4.28 (m, 1H), 4.12 (app q, J=6.9 Hz, 1H), 4.04-3.89 (m, 2H), 3.77 (s, 1H), 3.51-3.42 (m, 0.7H), 3.30-3.20 (m, 0.3H), 2.60-2.53 (m, 1H), 1.76-1.63 (m, 6H), 1.44 (s, 9H), 1.19-1.05 (m, 5H) ppm. Mass spectrum, m/z [603.4] (M+H)+.

後処理

  1. temperaturethe reaction mixture was warmed to ambient temperature
  2. washthe resulting organic solution was washed successively with 1M HCl and brine
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was purified by flash silica gel chromatography (1:1 hexanes/EtOAc to 1:2 hexanes/EtOAc)

出典と根拠

ORDレコード
ord-e1fff0a1f60b494c8fd617083cbe3fce
出典データセット
uspto-grants-2013_03
特許番号
US08399683B2

反応ノート

読み込み中…