Diisopropylethylamine → 2-(3-Fluoro-phenyl)-pyrimidine-5-carboxylic acid (6-fluoro-2,3-dihydro-1,4-benzoxazin-4-yl)-amide

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Reaction Steps

DIPEA (174 μL) is added to a mixture of 2-(3-fluoro-phenyl)-pyrimidine-5-carboxylic acid (218 mg), HATU (380 mg) and 6-fluoro-2,3-dihydro-benzo[1,4]oxazin-4-ylamine (220 mg) in DMF (15 mL) and then heated at 800 C. overnight. The reaction mixture is concentrated in vacuo and the residue is purified by silica gel column chromatography eluting with 30% EtOAc in heptane to afford 2-(3-fluoro-phenyl)-pyrimidine-5-carboxylic acid (6-fluoro-2,3-dihydro-1,4-benzoxazin-4-yl)-amide (81 mg). MS: 369 (M+H); 1H NMR (300 MHz, DMSO-D6): δ 11.05 (s, 1H), 9.35 (s, 2H), 8.32 (dd, 1H), 8.18 (dd, 1H), 7.65 (m, 1H), 7.5 (m, 1H), 6.8-6.7 (m, 2H), 6.52-6.45 (m, 1H), 4.36-4.33 (m, 2H), 3.65 (m, 2H). IC50=12 nM.

Provenance & Evidence