反应详情

A solution of 4-[4-(6-Fluoro-pyrido[3,4-d]pyrimidin-4-ylamino)-2-methyl-phenoxy]-piperidine-1-carboxylic acid tert-butyl ester (1.0 g, 2.21 mmol), NEt3 (0.67 g, 6.63 mmol), and morpholine (0.57 g, 6.63 mmol) in DMSO (10 mL) was heated to 120° C. in a sealed tube. After 24 h the reaction was diluted with EtOAc, the organic layer was washed 2× 1N NaOH and 2× water. The organic layer was treated with HCl (g) and the title compound was collected by filtration as a yellow solid (0.63 g, 67%). LRMS: 421.3 (MH+). 1H NMR (DMSO-d6, 400 MHz): δ 9.15 (br. s, 1H), δ 9.05 (br. s, 1H), δ 8.92 (s, 1H), δ 8.65 (s, 1H), δ 8.18 (s, 1H), δ 7.49-7.51 (m, 2H), δ 7.096 (d, J=9.55, 1H), δ 4.66-4.69 (m, 1H), δ 3.65-3.73 (m, 8H), δ 3.16 (br. s, 2H), δ 3.06 (br. s, 2H), δ 2.17 (s, 3H), δ 2.07-2.13 (m, 2H), δ 1.85-1.94 (m, 2H).

1. washthe organic layer was washed 2× 1N NaOH and 2× water
2. additionThe organic layer was treated with HCl (g)
3. filtrationthe title compound was collected by filtration as a yellow solid (0.63 g, 67%)