Morpholine → HCID 11178974, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 4-[6-(4-bromo-2-fluoro-phenoxy)-5-methyl-pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester (Compound C130, 500 mg, 1.07 mmole), morpholine (121 mg, 1.39 mmole), palladium acetate (3 mg, 0.011 mmole), biphenyl-2-yl-di-tert-butyl-phosphane (4 mg, 0.012 mmole) and sodium t-butoxide (257 mg, 2.14 mmole) in dioxane (3 mL) was heated under microwave irradiation at 150° C. for 1 hours. The crude mixture was purified by HPLC to provide Compound C3 as a yellow oil (235 mg, 46%). 1H NMR (CDCl3, 400 MHz) δ 1.28 (d, J=6.3 Hz, 6H), 1.81-1.85 (m, 2H), 1.99-2.04 (m, 2H), 2.20 (s, 3H), 3.44-3.47 (m, 2H), 3.49-3.51 (m, 4H), 3.73-3.78 (m, 2H), 4.08-4.10 (m, 2H), 4.95 (sep, J=6.3 Hz, 1H), 5.35-5.37 (m, 1H), 7.25 (d, J=10.1 Hz, 2H), 7.32 (t, J=8.6 Hz, 1H), 8.26 (s, 1H). Exact mass calculated for C24H31FN4O5 474.2, found 475.4 (MH+).

Provenance & Evidence