Potassium Phosphate, Tribasic → 2-{(2-Methoxyethyl)[(trans-2-methylcyclopropyl)methyl]amino}-6-[methyl(methylsulfonyl)amino]isonicotinic acid

Participants

Reaction Conditions

Reaction Steps

A suspension of 2-chloro-6-[methyl(methylsulfonyl)amino]isonicotinic acid (20 g, 75.6 mmol), trans (2-methoxyethyl)[(2-methylcyclopropyl)methyl]amine hydrochloride (17.65 g, 98.2 mmol), potassium phosphate (48.12 g, 226.7 mmol) in DMA (300 mL) was degassed with argon for 10 min. Pd(PtBu3)2 (1.93 g, 3.78 mmol) was added and the reaction mixture was degassed with argon for 10 min. The reaction mixture was stirred at 110° C. for 24 hours. The reaction was cooled to rt, filtered through celite, rinsed with EtOAc, diluted with water, the pH was adjusted to 3-4 with 1N HCl, extracted with EtOAc (×3). The organic layer was washed with aq LiCl, dried over sodium sulfate and concentrated in vacuo to give 2-{(2-methoxyethyl)[(trans-2-methylcyclopropyl)methyl]amino}-6-[methyl(methylsulfonyl)amino]isonicotinic acid. 1H NMR (400 MHz, CDCl3) δ 7.05 (s, 1H), 7.62 (s, 1H), 3.76 (t, J=6.3 Hz, 2H), 3.60 (t, J=6.3 Hz, 2H), 3.52-3.43 (m, 1H), 3.39 (s, 3H), 3.36 (s, 3H), 3.38-3.30 (m, 1H), 3.18 (s, 3H), 1.23 (d, J=6.1 Hz, 3H), 0.82-0.64 (m, 2H), 0.46-0.39 (m, 1H), 0.32-0.25 (m, 1H).

Provenance & Evidence