Hydrogen Peroxide → HCID 178458668, compound

HRID 75869Notes

Reaction equation

[F:1][C:2]1[C:3]([NH:21][C:22]2[CH:26]=[C:25]([O:27][CH:28]([CH3:30])[CH3:29])[NH:24][N:23]=2)=[N:4][C:5]([NH:10][C@H:11]([C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=2)[CH2:12][OH:13])=[C:6]([CH:9]=1)[C:7]#[N:8].[OH-:31].[K+].OO>CO>[F:1][C:2]1[C:3]([NH:21][C:22]2[CH:26]=[C:25]([O:27][CH:28]([CH3:30])[CH3:29])[NH:24][N:23]=2)=[N:4][C:5]([NH:10][C@H:11]([C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=2)[CH2:12][OH:13])=[C:6]([CH:9]=1)[C:7]([NH2:8])=[O:31]

Participants

Conditions

Temperature: 65 °C

Procedure

(R)-5-Fluoro-2-(1-(4-fluorophenyl)-2-hydroxyethylamino)-6-(5-isopropoxy-1H-pyrazol-3-ylamino)nicotinonitrile (Example 11; 0.06 g, 0.1 mmol) was placed in MeOH (5 ml) at 25° C. A 25% aqueous solution (0.2 ml) of KOH (0.05 g, 0.7 mmol) was then added, followed by the addition of 0.05 ml of 30% H2O2. The resulting dark red solution was heated to 65° C. for 1 h, cooled to 25° C., and concentrated. The resulting residue was dissolved in EtOAc (50 ml), washed with water (30 ml), dried, filtered, and concentrated. The resulting solid was purified by column chromatography (DCM-MeOH=30:1) to give the title compound (0.037 g, 60%). 1H NMR (400 MHz, CD3OD) δ 7.75 (d, J=11.9 Hz, 1H), 7.43-7.39 (m, 2H), 7.06-7.02 (m, 2H), 5.37 (br s, 1H), 5.10-5.02 (m, 1H), 4.60-4.54 (m, 1H), 3.90-3.86 (m, 1H), 3.79-3.74 (m, 1H), 1.32 (d, J=6.0 Hz, 6H). MS: Calcd.: 432. Found: [M+H]+433.

Workup

temperaturecooled to 25° C.
concentrationconcentrated
dissolutionThe resulting residue was dissolved in EtOAc (50 ml)
washwashed with water (30 ml)
customdried
filtrationfiltered
concentrationconcentrated
customThe resulting solid was purified by column chromatography (DCM-MeOH=30:1)

Sources & evidence

ORD record: ord-a95106f054184a56991cecb945c662c6
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08835465B2

Reaction notes

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