Lithium Chloride → 5-(4-(benzyloxy)-3-fluorophenyl)-2-(cyclopropylmethylamino)-3-methylpyrimidin-4(3H)-one

Participants

Reaction Conditions

Reaction Steps

A suspension of 5-bromo-2-(cyclopropylmethylamino)-3-methylpyrimidin-4(3H)-one (0.112 g, 0.434 mmol), 4-(benzyloxy)-3-fluorophenylboronic acid (0.128 g, 0.521 mmol), Pd(PPh3)4 (0.025 g, 0.022 mmol) and lithium chloride (0.092 g, 2.17 mmol) in dioxane (1.5 mL) and 2M aqueous Na2CO3 (1.5 mL) was stirred at 100° C. for 30 minutes. The reaction mixture was cooled to room temperature and then partitioned between EtOAc and H2O. The phases were separated, and the aqueous phase was re-extracted with EtOAc (1×). The combined organic layers were dried (Na2SO4), filtered and concentrated to yield a crude black solid. The crude product was purified by flash column chromatography, eluting with 10:1 dichloromethane/EtOAc. The desired product (0.128 g, 78%) was obtained as a foamy off-white solid. 1H NMR (400 MHz, DMSO-d6) δ 7.93 (s, 1H), 7.57 (dd, J=2.0, 13.7 Hz, 1H), 7.49-7.31 (m, 7H), 7.19 (t, J=9.0 Hz, 1H), 5.19 (s, 2H), 3.35 (s, 3H), 3.24 (t, J=6.1 Hz, 2H), 1.16 (m, 1H), 0.44 (m, 2H), 0.25 (m, 1H). LRMS (APCI pos) m/e 380 (M+1).

Provenance & Evidence