Diisopropylethylamine → (E)-N-(2-(5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-1H-indol-1-yl)-2-oxoethyl)-3,3,3-trifluoropropanamide

HRID 1502707ノート

反応式

HRID 1502707 の反応式
[NH2:1][CH2:2][C:3]([N:5]1[C:13]2[C:8](=[CH:9][C:10](/[CH:14]=[CH:15]/[CH:16]([C:21]3[CH:26]=[C:25]([Cl:27])[C:24]([F:28])=[C:23]([Cl:29])[CH:22]=3)[C:17]([F:20])([F:19])[F:18])=[CH:11][CH:12]=2)[CH:7]=[CH:6]1)=[O:4].[F:30][C:31]([F:37])([F:36])[CH2:32][C:33](O)=[O:34].C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C(Cl)Cl>[Cl:27][C:25]1[CH:26]=[C:21]([CH:16]([C:17]([F:19])([F:20])[F:18])/[CH:15]=[CH:14]/[C:10]2[CH:9]=[C:8]3[C:13](=[CH:12][CH:11]=2)[N:5]([C:3](=[O:4])[CH2:2][NH:1][C:33](=[O:34])[CH2:32][C:31]([F:37])([F:36])[F:30])[CH:6]=[CH:7]3)[CH:22]=[C:23]([Cl:29])[C:24]=1[F:28]

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 27779723,3,3-Trifluoropropionic acidHCID 86675170(E)-2-amino-1-(5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-1H-indol-1-yl)ethanone

生成物 1

HCID 86675172(E)-N-(2-(5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-1H-indol-1-yl)-2-oxoethyl)-3,3,3-trifluoropropanamide収率 60%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

To a stirred solution of (E)-2-amino-1-(5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-1H-indol-1-yl) ethanone (0.04 g, 0.09 mmol) in CH2Cl2 (5.0 ml) was added 3,3,3-trifluoropropanoic acid (17.5 mg, 0.136 mmol), PyBOP (70 mg, 0.135 mmol) and DIPEA (29 mg, 0.225 mmol) and the reaction was stirred at ambient temperature for 16 h. The reaction mixture was diluted with CH2Cl2, and the CH2Cl2 layer was washed with water and saturated brine solution. The separated CH2Cl2 layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure to afford the crude compound, which was purified by column chromatography (SiO2, 100-200 mesh; 10% ethyl acetate/petroleum ether) to afford the title compound as an off-white solid (30 mg, 60%): mp 121-126° C.; 1H NMR (400 MHz, CDCl3) δ 8.33 (br, 1H), 7.59 (s, 1H), 7.45 (m, 4H), 6.72 (d, J=3.6 Hz, 3H), 6.39 (m, 1H), 4.71 (t, J=7.2 Hz, 2H), 4.15 (m, 1H), 3.51 (m, 1H), 3.28 (m, 1H); ESIMS m/z 553.06 ([M−H]−).

後処理

  1. washthe CH2Cl2 layer was washed with water and saturated brine solution
  2. dry with materialThe separated CH2Cl2 layer was dried over anhydrous Na2SO4
  3. concentrationconcentrated under reduced pressure
  4. customto afford the crude compound, which
  5. customwas purified by column chromatography (SiO2, 100-200 mesh; 10% ethyl acetate/petroleum ether)

出典と根拠

ORDレコード
ord-86e6408474b34563b0bab5cee256d73d
出典データセット
uspto-grants-2015_12
特許番号
US09210927B2

反応ノート

読み込み中…