Potassium Phosphate, Tribasic → Tert-butyl 5-(2-{[(1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl]methoxy}-1,5-naphthyridin-3-yl)-3,6-dihydropyridine-1 (2H)-carboxylate

Participants

Reaction Conditions

Reaction Steps

A mixture of 3-bromo-2-{[(1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl]-methoxy}-1,5-naphthyridine (LL2) (50 mg, 0.13 mmol), tert-butyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydropyridine-1(2H)-carboxylate (52 mg, 0.17 mmol), tripotassium phosphate (55 mg, 0.26 mmol), S-Phos (5.3 mg, 0.01 mmol), and Pd(OAc)2 (1.5 mg, 0.006 mmol) in THF (0.6 mL) and water (0.1 mL) was heated at 100° C. for 14 hours. The reaction mixture was allowed to cool to room temperature. The mixture was then diluted with EtOAc (5 mL), washed with sodium bicarbonate (1 mL) and brine (1 mL), dried over MgSO4, filtered and concentrated. The resulting residue was purified by reverse phase chromatography (Waters Sunfire Prep C18 OBD, 5-60% acetonitrile in water with 0.1% TFA modifier) to afford the title compound. 1H NMR (500 MHz, DMSO): δ 8.79 (dd, J=4.3, 1.6 Hz, 1 H), 8.18-8.06 (m, 3 H), 7.66 (dd, J=8.4, 4.2 Hz, 1 H), 7.24 (s, 2 H), 6.26 (s, 1 H), 4.54 (m, 1 H), 4.44 (m, 1 H), 4.26 (brs, 2 H), 3.77 (s, 3 H), 3.49-3.40 (m, 2 H), 2.27 (s, 2 H), 2.24-2.19 (m, 1 H), 1.80 (s, 1 H), 1.41 (s, 9 H), 1.23-1.15 (m, 2 H), 1.08 (dt, J=8.7, 4.6 Hz, 1 H); HRMS m/z (M+H) 489.2486 found, 489.2496 required.

Provenance & Evidence