Morpholine → HCID 16117890, compound

Participants

Reaction Steps

A mixture of (2R)-2-[(4-{[1-(1,3-thiazol-4-ylmethyl)-1H-indazol-5-yl]amino}quinazolin-5-yl)oxy]propanoic acid (250 mg, 0.56 mmol), 2-hydroxypyridine-N-oxide (124 mg, 1.1 mmol), morpholine (0.098 ml, 1.1 mmol), diisopropylethylamine (0.195 ml, 1.1 mmol) and EDCI (214 mg, 1.1 mmol) in DMF (2 ml) was stirred at room temperature for 18 hours. Additional coupling agents were added (1 equivalent) and the mixture was stirred for 2 hours more. The reaction mixture was directly injected on an HPLC column (C18, 5 microns, 20 mm diameter, 100 mm length) of a preparative HPLC-MS system eluting with a mixture of water and acetonitrile containing 2 g/l of ammonium carbonate (gradient) to give the title compound as a white solid (180 mg, 62%); NMR Spectrum 1.58 (d, 3H), 3.70-3.40 (m, 8H), 5.79 (s, 2H), 5.88 (q, 1H), 7.29 (d, 1H), 7.35 (s, 1H), 7.51 (s, 1H), 7.75 (m, 2H), 7.84 (m, 1H), 8.10 (s, 1H), 8.51 (s, 2H), 9.04 (s, 1H), 11.12 (br s, 1H); Mass spectrum: MH+ 516.

Provenance & Evidence