Potassium Carbonate → HCID 72192439, compound

Participants

Reaction Conditions

Reaction Steps

Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (11.20 mg, 0.016 mmol) was added to a degassed dioxane (700 μl)/Water (100 μl) solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[5-(5-chloro-2-methoxypyridin-3-yl)-2-(morpholin-4-yl)pyrimidin-4-yl]methyl}-4-methyl-1,3-oxazolidin-2-one (EXAMPLE 11, 100 mg, 0.158 mmol), potassium cyclopropyltrifluoroborate (46.8 mg, 0.316 mmol) and K2CO3 (65.6 mg, 0.475 mmol). After further degassing with N2 and vacuum for 3 cycles, the reaction was capped and stirred for 30 minutes at 130° C. in a Biotage microwave reactor. LCMS showed >80% conversion to product. The reaction was diluted with 5 mL acetonitrile and filtered through a 1 g RP C18 silica cartridge, eluting with 15 mL acetonitrile until the filtrate was colorless. The filtrate was concentrated and the crude purified under the following conditions: X-Bridge 21.2×150 mm RP column, sample loaded in 7:3:1 CH3CN/water/DMSO (5 mL) with the column eluted using a 10-100% acetonitrile/water (0.1% NH4OH) linear gradient at 15 mL/minute over 20 minutes to give the product as a white solid after lyophilization of the purified fractions. LCMS (M+H)+: 638.5. 1H NMR (500 MHz, CDCl3): δ 8.23 (br, 1H), 8.12 (br, 1H), 7.93 (br, 1H), 7.75 (br, 2H), 7.24 (br, 1H), 5.68 (m, 2H), 4.72 (d, J=17.6 Hz, 1H), 4.13 (d, J=17.6 Hz, 1H), 4.07 (m, 4H), 3.99 (s, 3H), 3.88 (m, 4H), 1.93 (m, 1H), 1.05 (m, 2H), 0.71 (m, 5H). SPA IC50: 530 nM

Provenance & Evidence