Hydrogen Peroxide → 8-Fluoro-1-{[(1R,2R,4R)-4-hydroxy-2-methylcyclohexyl]amino}-5H-pyrido[4,3-b]indole-4-carboxamide

HRID 1971018Notes

Reaction equation

[F:1][C:2]1[CH:10]=[CH:9][C:8]2[NH:7][C:6]3[C:11]([C:24]#[N:25])=[CH:12][N:13]=[C:14]([NH:15][C@@H:16]4[CH2:21][CH2:20][C@@H:19]([OH:22])[CH2:18][C@H:17]4[CH3:23])[C:5]=3[C:4]=2[CH:3]=1.OO.C(=O)([O-])[O-:29].[K+].[K+]>CS(C)=O.[Cl-].[Na+].O>[F:1][C:2]1[CH:10]=[CH:9][C:8]2[NH:7][C:6]3[C:11]([C:24]([NH2:25])=[O:29])=[CH:12][N:13]=[C:14]([NH:15][C@@H:16]4[CH2:21][CH2:20][C@@H:19]([OH:22])[CH2:18][C@H:17]4[CH3:23])[C:5]=3[C:4]=2[CH:3]=1

Participants

Conditions

Temperature: 70 °C

Procedure

To a stirred solution of 8-fluoro-1-{[(1R,2R,4R)-4-hydroxy-2-methylcyclohexyl]amino}-5H-pyrido[4,3-b]indole-4-carbonitrile (4.8 g, 14.2 mmol) in DMSO (100 mL) were added hydrogen peroxide (30%, 14.5 mL, 142 mmol) and potassium carbonate (10.6 g, 77 mmol). The reaction mixture was heated to 70° C. overnight, cooled to room temperature, treated with brine, and extracted with EtOAc (×3). The combined organics were dried, concentrated, and purified by flash chromatography to afford the title compound. 1H NMR (600 MHz, CD3OD) δ 8.43 (s, 1H); 7.94 (dd, 1H); 7.57 (dd, 1H); 7.13 (dt, 1H); 3.98 (m, 1H); 3.67 (m, 1H); 1.22-2.12 (series of m, 7H); 1.01 (d, 3H). LRMS (APCI) calc'd for (C19H21FN4O2) [M+H]+, 357.2. found 357.1.

Workup

temperaturecooled to room temperature
extractionextracted with EtOAc (×3)
customThe combined organics were dried
concentrationconcentrated
custompurified by flash chromatography

Sources & evidence

ORD record: ord-168ef28045ac457c97be2f49b92e7357
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08431569B2

Reaction notes

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