Dimethyl Sulfoxide → 7-Chloro-1-{[(1R)-1-cyclopropyl-2,2,2-trifluoroethyl]amino}-5H-pyrido[4,3-b]indole-4-carboxamide

HRID 1970995Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[C:6]3[C:14]([NH:15][C@H:16]([CH:21]4[CH2:23][CH2:22]4)[C:17]([F:20])([F:19])[F:18])=[N:13][CH:12]=[C:11]([C:24]#[N:25])[C:7]=3[NH:8][C:9]=2[CH:10]=1.C(=O)([O-])[O-:27].[K+].[K+].CS(C)=O.OO>CCOC(C)=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[C:6]3[C:14]([NH:15][C@H:16]([CH:21]4[CH2:22][CH2:23]4)[C:17]([F:18])([F:20])[F:19])=[N:13][CH:12]=[C:11]([C:24]([NH2:25])=[O:27])[C:7]=3[NH:8][C:9]=2[CH:10]=1

Participants

Conditions

Temperature: 80 °C

Procedure

7-Chloro-1-{[(1R)-1-cyclopropyl-2,2,2-trifluoroethyl]amino}-5H-pyrido[4,3-b]indole-4-carbonitrile (4.48 g, 12.3 mmol) and potassium carbonate (8.49 g, 61.4 mmol) were placed in a flask. DMSO (246 ml) and 30% hydrogen peroxide (12.55 ml, 123 mmol) were added and the solution heated at 80° C. for 2 h. Additional 30% hydrogen peroxide (12.55 mL, 123 mmol) and potassium carbonate (8.49 g, 61.4 mmol) were added. The resultant mixture was heated to 80° C. for 2 h, cooled to room temperature, and diluted with EtOAc. The mixture was washed with water and brine, dried (magnesium sulfate), concentrated, and purified by flash chromatography to give the title compound. 1H NMR (600 MHz, CD3SOCD3) δ 11.81 (s, 1H); 8.54 (s, 1H); 8.50 (d, 1H); 7.96 (br s, 1H); 7.80 (d, 1H); 7.33 (br s, 1H); 7.30 (dd, 1H); 7.07 (d, 1H); 4.86 (m, 1H); 1.59 (m, 1H); 0.76 (m, 1H); 0.64 (m, 1H); 0.54 (m, 1H); 0.33 (m, 1H). LRMS (APCI) calc'd for (C17H14ClF3N4O) [M+H]+, 383.1. found 383.0.

Workup

temperaturecooled to room temperature
washThe mixture was washed with water and brine
dry with materialdried (magnesium sulfate)
concentrationconcentrated
custompurified by flash chromatography

Sources & evidence

ORD record: ord-e479cc9172544887b104ae063f7f640c
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08431569B2

Reaction notes

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