Hydrogen Peroxide → HCID 178458647, compound

HRID 75874Notes

Reaction equation

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

Participants

Conditions

Temperature: 65 °C

Procedure

(S)-5-Fluoro-2-(1-(4-fluorophenyl)ethylamino)-6-(5-isopropoxy-1H-pyrazol-3-ylamino)nicotinonitrile (Example 16; 0.15 g, 0.38 mmol), was placed in MeOH (7 ml) at 25° C. A 25% aqueous solution (0.4 ml) of KOH (0.11 g, 1.9 mmol) was then added, followed by the addition of 0.1 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=25:1) to give the title compound (0.044 g, 28%). 1H NMR (400 MHz, CD3OD) δ 7.75 (d, J=11.7 Hz, 1H), 7.39-7.36 (m, 2H), 7.04-7.00 (m, 2H), 5.37 (s, 1H), 5.11-5.00 (m, 1H), 4.61-4.52 (m, 1H), 1.53 (d, J=7.0 Hz, 3H), 1.31 (m, 6H). MS: Calcd.: 416. Found: [M+H]+417.

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=25:1)

Sources & evidence

ORD record: ord-0b48bfd27df448dd93cc85882f47aea0
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08835465B2

Reaction notes

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