Cesium carbonate → diethyl (4-{[4-({6-[1-(3-hydroxypropyl)-1H-pyrazol-4-yl]-2-(methylcarbamoyl)pyridin-3-yl}amino)-5-(trifluoromethyl)pyridin-2-yl]amino}-3-methoxybenzyl)phosphonate

Participants

Reaction Steps

A solution of 3-{[2-chloro-5-(trifluoromethyl)pyridin-4-yl]amino}-6-[1-(3-hydroxypropyl)-1H-pyrazol-4-yl]-N-methylpyridine-2-carboxamide (Compound 36C, 158 mg, 0.35 mmol) and diethyl (4-amino-3-methoxybenzyl)phosphonate (Compound 1F, 104 mg, 0.38 mmol) in 1,4-dioxane (4.0 mL) was treated with Pd(II)(OAc)2 (3.90 mg, 0.017 mmol), Xantphos (20.1 mg, 0.035 mmol) and Cs2CO3 (226 mg, 0.70 mmol). The mixture was purged with N2 for 2 minutes, sealed and irradiated in a microwave reactor for 40 minutes at 120° C. The cooled reaction mixture was poured into water and extracted twice with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated to a brown residue which was taken purified using a Teledyne ISCO Combiflash® system (0%-5%-10% MeOH/DCM) to afford 27 mg of a brown foam (11%). 1H NMR (400 MHz, CDCl3) δ 10.91 (s, 1H), 8.38 (s, 1H), 8.23 (q, J=5.6 Hz, 1H), 7.98 (s, 1H), 7.98 (s, 1H), 7.86 (d, J=8.8 Hz, 1H), 7.76 (d, J=7.8 Hz, 1H), 7.51 (d, J=8.6 Hz, 1H), 6.86-6.94 (m, 3H), 6.70 (s, 1H), 4.38 (t, J=6.3 Hz, 2H), 3.93-4.05 (m, 4H), 3.88 (s, 3H), 3.66 (q, J=5.5 Hz, 2H), 3.12 (d, J=21.2 Hz, 2H), 3.06 (d, J=5.1 Hz, 3H), 2.79 (t, J=5.2 Hz, 1H), 2.13 (quin, J=6.1 Hz, 2H), 1.21 (t, J=7.0 Hz, 6H).

Provenance & Evidence