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 1503707노트

반응식

HRID 1503707 반응식
[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]

참가 물질

6

반응물 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

생성물 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-trifluoropropanamide수율 60%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

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 DCM (5.0 ml) was added 3,3,3-trifluoropropanoic acid (17.5 mg, 0.136 mmol), PyBOP (70 mg, 0.135 mmol) and DIEA (29 mg, 0.225 mmol) and the reaction was stirred at RT for 16 h. The reaction mixture was diluted with DCM, and the DCM layer was washed with water and saturated brine solution. The separated DCM 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]−).

후처리

  1. washthe DCM layer was washed with water and saturated brine solution
  2. dry with materialThe separated DCM 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)

출처 및 근거

ORD 기록
ord-3a4182660ca549f482bbdc30011ad447
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09212164B2

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