1-Butanol → N-{5-[1-({3-Cyano-6-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]-5-fluoropyridin-2-yl}amino)ethyl]-2-fluorophenyl}cyclopropanecarboxamide

Participants

Reaction Conditions

Reaction Steps

To a 10-ml microwave reaction vessel was added 6-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]-2,5-difluoronicotinonitrile (Method 32, 431 mg, 1.65 mmol), N-[5-(1-aminoethyl)-2-fluorophenyl]cyclopropanecarboxamide (Method 69, 550 mg, 2.5 mmol), and DIEA (1.15 ml, 6.6 mmol) in n-butanol (5 ml). The resulting suspension was set to microwave heating (CEM Discover System) at 150° C. for 3 hours. The reaction was concentrated in vacuo and purified by silica gel chromatography (Biotage Horizon System) using a gradient elution of 25-35% EtOAc (20% v/v MeOH) in hexanes to give 267 mg (35% isolated yield) of the title compound. 1H NMR: 11.99 (s, 1H) 9.91 (s, 1H) 9.42 (s, 1H) 7.88 (d, J=6.03 Hz, 1H) 7.59 (d, J=10.55 Hz, 1H) 6.95-7.20 (m, 3H) 5.99 (s, 1H) 5.02-5.21 (m, 1H) 1.89-2.03 (m, 1H) 1.76-1.89 (m, 1H) 1.45 (d, J=7.54 Hz, 3H) 0.87 (t, J=8.67 Hz, 2H) 0.75 (d, J=6.03 Hz, 4H) 0.54-0.66 (m, 2H). MS: Calcd.: 463. Found: [M+H]+ 464.

Provenance & Evidence