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

HRID 1092247Notes

Reaction equation

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

Participants

Conditions

Temperature: 230 °C

Procedure

A mixture of 3-(5-cyclopropyl-1H-pyrazol-3-ylamino)-5-fluoro-2-nitrobenzonitrile (Method 98, 3.50 g, 12.2 mmol), (S)-1-(4-fluoro-phenyl)ethylamine (1.87 g, 13.4 mmol), and DIEA (2.6 ml, 14.6 mmol) in n-BuOH (20 ml) was heated in a sealed tube at 230° C. for 2 hours. The solvent was removed under reduced pressure and the residue was purified by column chromatography (hexane-EtOAc=1:2) to give the title compound as a yellow solid (4.4 g, 89%). 1H NMR (400 MHz) 12.38 (s, 1H), 10.12 (b, 1H), 8.07 (d, J=6.4 Hz, 1H), 7.34 (m, 2H), 7.16 (m, 2H), 6.89 (b, 1H), 6.77 (s, 1H), 5.63 (m, 1H), 4.55 (m, 1H), 1.90 (m, 1H), 1.45 (d, J=6.8 Hz, 3H), 0.97 (m, 2H), 0.70 (m 2H). MS: Calcd.: 406; Found: [M+H]+ 407.

Workup

customThe solvent was removed under reduced pressure
customthe residue was purified by column chromatography (hexane-EtOAc=1:2)

Sources & evidence

ORD record: ord-dda31f0bd2f44141990eb9160607fed4
Source dataset: uspto-grants-2012_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08129403B2

Reaction notes

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