Nitrogen → 2-(2-Chloro-5-cyclopropyl-pyridin-4-ylamino)-N-methyl-benzamide

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Reaction Steps

A solution of cyclopropylboronic acid (0.38 g, 4.40 mmole, 1.5 eq) in toluene (100 mL) was degassed with N2 at 50° C. for 15 min. To this was added Pd(PPh3)4 (0.17 g, 0.15 mmole, 0.05 eq) and 2-(5-bromo-2-chloro-pyridin-4-ylamino)-N-methyl-benzamide (1 g, 2.93 mmole, 1 eq) and the resulting reaction mixture was again degassed for 30 min. To this a degassed solution K3PO4 (2.49 g, 11.72 mmole, 4 eq) in H2O (4 mL) was added in one portion and the resulting reaction mixture was refluxed for overnight. Solvent was removed under reduced pressure and the residue was diluted with water (100 mL) and then extracted with DCM (3×75 mL). Combined organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure to yield crude product. Crude compound was purified by column chromatography over silica gel (60-120 mesh) using 0.5% MeOH-DCM as the eluant to give the title compound as a pale yellow solid (0.480 g, 54%). 1H-NMR (400 MHz, DMSO-d6): δ 0.60-0.70 (m, 2H), 0.95-1.05 (m, 2H), 1.60-1.71 (m, 1H), 2.76 (d, 3H, J=4.48 Hz), 7.09 (s, 1H), 7.10-7.18 (m, 1H), 7.49-7.60 (m, 2H), 7.68-7.70 (d, 1H, J=7.64 Hz), 7.93 (s, 1H), 8.60-8.70 (m, 1H), 10.22 (s, 1H). LC-MS [M+H]+=302.0.

Provenance & Evidence