2-Fluoroaniline → 5-cyclopropyl-2-{4-[(2-fluorophenyl)amino]phenyl}-6-[(3-hydroxypropyl)(methylsulfonyl)amino]-N-methyl-2H-indazole-3-carboxamide

Participants

Reaction Conditions

Reaction Steps

A mixture of Compound (4) (16 mg, 31 μmol), 2-fluoroaniline (4.4 μL, 46 μmol), 2,2′-bis(diphenylphosphino)-1,1′-binaphthalene (4 mg, 6 μmol) and cesium carbonate (30 mg, 92 μmol) in toluene (0.5 mL) and 1,2-dimethoethane (0.2 mL) was placed in a high pressure vial. Nitrogen was bubbled through the mixture for ˜20 min. Palladium acetate (0.7 mg, 3 μmol) was then added and the vial was sealed. The mixture was heated to 100° C. and stirred for 16 h. After cooling to RT, the mixture was diluted with EtOAc (10 mL) and filtered through a pad of Celite®. The filtrate was concentrated in vacuo to give a crude mixture which was purified by flash column chromatography eluting with MeOH/DCM (0-20%). Further purification was done by preparative HPLC to give Compound (5) (3.68 mg, 22%) as a pale yellow solid. ESI-MS m/z calculated for [M+H]+: 552.21; found: 552.14. 1H NMR (400 MHz, CDCl3) δ 7.73 (s, 1H), 7.52 (s, 1H), 7.49-7.43 (m, 2H), 7.41 (dt, J=8.2, 1.5 Hz, 1H), 7.20-7.07 (m, 4H), 7.04-6.93 (m, 1H), 6.01 (brd, J=1.8 Hz, 1H), 5.71 (brd, J=4.6 Hz, 1H), 4.02-3.63 (m, 4H), 3.07 (s, 3H), 2.95 (d, J=4.9 Hz, 3H), 2.51-2.25 (m, 1H), 1.87-1.74 (m, 2H), 1.13-0.94 (m, 3H), 0.74-0.55 (m, 1H).

Provenance & Evidence