Diisopropylethylamine → (S)-6-(5-cyclopropyl-1H-pyrazol-3-ylamino)-5-fluoro-2-(1-(4-fluorophenyl)ethylamino)nicotinonitrile

HRID 75858

Reaction equation

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

Participants

Conditions

Temperature: 140 °C

Procedure

A portion of 2-chloro-6-(5-cyclopropyl-1H-pyrazol-3-ylamino)-5-fluoronicotinonitrile (Method 1; 0.8 g, 2.8 mmol) and (S)-1-(4-fluorophenyl)ethanamine (0.8 g, 5.6 mmol) were added to a solution of n-BuOH (4 ml) and DIEA (0.5 g, 3.7 mmol) in a sealed tube. The reaction was heated to 140° C. for 48 hrs, then cooled to 25° C. and concentrated. The resulting residue was purified by column chromatography (DCM-MeOH=50:1) to give the title compound (0.55 g, 50%). 1H NMR (400 MHz, CDCl3) δ 8.44 (br s, 1H), 7.37-7.33 (m, 2H), 7.27 (d, J=9.6 Hz, 1H), 7.07-7.03 (m, 2H), 6.11 (s, 1H), 5.24-5.20 (m, 2H), 1.87-1.83 (m, 1H), 1.60 (d, J=6.2 Hz, 3H), 1.01-0.98 (m, 2H), 0.79-0.65 (m, 2H). MS: Calcd.: 380. Found: [M+H]+ 381.

Workup

temperaturecooled to 25° C.
concentrationconcentrated
customThe resulting residue was purified by column chromatography (DCM-MeOH=50:1)

Sources & evidence

ORD record: ord-41a00db91be147f193b0d6ff37dd0507
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08835465B2

Linked notes

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