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 1503536Notes

Reaction equation

HRID 1503536 reaction equation
[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]

Participants

6

Reactant 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

Product 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-trifluoropropanamideYield 60%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

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]−).

Workup

  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)

Sources & evidence

ORD record
ord-d49367d5c68b417ea6981ca32e26557c
Source dataset
uspto-grants-2015_12
Patent number
US09212163B2

Reaction notes

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