Cesium carbonate → N-(3-(3-amino-4-fluorophenyl)-2-methyl-1,6-naphthyridin-7-yl)cyclopropanecarboxamide

Participants

Reaction Conditions

Reaction Steps

Sparge a solution of 5-(7-chloro-2-methyl-1,6-naphthyridin-3-yl)-2-fluoroaniline (0.5 g, 1.738 mmol) in dioxane (15 mL) with argon, add cyclopropanecarboxamide (0.739 g, 8.69 mmol), XantPhos (0.101 g, 0.174 mmol), Cs2CO3 (1.699 g, 5.21 mmol) and Pd2(dba)3 (0.080 g, 0.087 mmol) and heat at 80° C. overnight. Cool to RT, add EtOAc and MeOH, remove the solids via filtration through diatomaceous earth, rinse well with EtOAc and H2O and separate the layers of the filtrate. Wash the organic layer with brine, dry over Na2SO4, concentrate to dryness and purify via silica gel chromatography (EtOAc/Hex) to afford the title compound (200 mg, 34%) as a white amorphous solid. 1H NMR (400 MHz, DMSO-d6): δ 11.01 (s, 1H), 9.13 (d, J=0.9 Hz, 1H), 8.44 (m, 1H), 8.17 (s, 1H), 7.08 (m, 1H), 6.82 (dd, J=8.7, 2.2 Hz, 1H), 6.59 (m, 1H), 5.28 (s, 2H), 2.56 (s, 3H), 2.02 (m, 1H), 0.88-0.81 (m, 4H); MS(ESI) m/z: 337.1 (M+H+).

Provenance & Evidence