A concentrated aqueous solution of hydrogen chloride (34-37.5%, 0.1 mL) was added at room temperature to a solution of methyl 3-(5-(N-(2-(tert-butyldimethylsilyloxy)ethyl)-4,6-dichloropyrimidine-5-carboxamido)pyridin-2-yloxy)-2,2-dimethylpropanoate B-19 (139.4 mg, 0.25 mmol) in methanol (2.0 mL). The reaction mixture was stirred for 30 mins at room temperature and concentrated to dryness under reduced pressure. The residue was dissolved in ethyl acetate, successively washed with a saturated aqueous solution of sodium bicarbonate and brine, dried over anhydrous sodium sulfate, filtered and concentrated to dryness under reduced pressure to give crude intermediate methyl 3-(5-(4,6-dichloro-N-(2-hydroxyethyl)pyrimidine-5-carboxamido)pyridin-2-yloxy)-2,2-dimethylpropanoate (MS (ESI) [M+1]+ 444), which was then dissolved in acetonitrile (2.0 mL). Triethylamine (0.14 mL, 1.0 mmol) was then added at room temperature, and the reaction mixture was heated at 100° C. for 3 h then concentrated to dryness under reduced pressure. The residue was dissolved in ethyl acetate, successively washed with water and brine, dried over anhydrous sodium sulfate, filtered and concentrated to dryness under reduced pressure to give methyl 3-(5-(4-chloro-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)pyridin-2-yloxy)-2,2-dimethylpropanoate B-20. This material was used for the next step without purification. MS (ESI) [M+1]+ 407.
