Diisopropylethylamine → 4-(3-fluoro-4-{[(quinoxalin-2-ylamino)carbonyl]amino}phenoxy)-N-methyl-pyridine-2-carboxamide

Participants

Reaction Conditions

Reaction Steps

To a solution of 4-[4-amino-3-(fluoro)phenoxy]-N-methylpyridine-2-carboxamide (150.0 mg, 0.57 mmol) in anhydrous THF (5.7 mL) was added triphosgene (63 mg, 0.21 mmol, 0.37 eq) and diisopropylethyl amine (0.12 mL, 0.69 mmol, 1.2 eq), and the reaction mixture was stirred at 75° C. After 3 h a solution of 2-aminoquinoxaline (83.3 mg, 0.57 mmol, 1.0 eq) in anhydrous DMF (2.8 mL) was added, and the reaction mixture was stirred at 75° C. for 17 h. The reaction mixture was partitioned between EtOAc and water, and the organic layer was washed with water and brine, dried over MgSO4, filtered, and evaporated under reduced pressure. The crude was absorbed onto silica and purified by MPLC (biotage) eluted with 10% MeOH/EtOAc. Trituration from DCM/MeOH afforded 25.0 mg (10.1%) of the title product as a yellow solid. 1H-NMR (DMSO-d6) δ 11.75 (s, 1H), 10.75 (s, 1H), 8.89 (s, 1H), 8.79 (br q, J=5.1 Hz, 1H), 8.53 (d, J=6.0 Hz, 1H), 8.38 (t, J=9.0 Hz, 1H), 8.01 (d, J=8.1 Hz, 1H), 7.82 (d, J=3.9 Hz, 2H), 7.70 to 7.64 (m, 1H), 7.47 to 7.42 (m, 2H), 7.20 (dd, J=5.4, 2.4 Hz, 1H), 7.14 (d, J=8.7 Hz, 1H) 2.78 (d, J=4.8 Hz, 3H); TLC (100% EA), Rf=0.20; MS LC-MS [M+H]+=433), RT=2.86 min.

Provenance & Evidence