反应详情

温度

120 °C

A suspension of 6-bromo-N-(5-cyano-4-((2-methoxyethyl)amino)pyridin-2-yl)-7-(dimethoxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide (intermediate 315, 50.9 mg, 0.101 mmol), 1-methylpyrazole-5-boronic acid pinacolester (23.9 mg, 0.111 mmol), PdCl2(dppf) (8 mg, 10.93 μmol) and saturated aqueous Na2CO3 (160 μl) in DME (480 μl) was sealed in a vial and purged with argon. Then reaction mixture was stirred at 120° C. for 15 min in a microwave. Additional 1-methylpyrazole-5-boronic acid pinacolester (10 mg, 0.047 mmol) and PdCl2(dppf) (8 mg, 10.93 μmol) were added and the reaction mixture was stirred in microwave for 15 min at 120° C. The suspension was diluted with DCM and water, phases were separated and the aqueous layer was extracted with DCM. The organic layers were combined, dried using Na2SO4, filtered and evaporated. The crude product was purified by silica gel column chromatography eluting with a gradient of MeOH (1-5%) in DCM. Product containing fractions were combined, evaporated and dried to yield the title compound as a yellow film. (UPLC-MS 3) tR 0.98 min; ESI-MS 507.2 [M+H]+.

1. customwas sealed in a vial and
2. custompurged with argon
3. customThen reaction mixture
4. stirringthe reaction mixture was stirred in microwave for 15 min at 120° C
5. customwere separated
6. extractionthe aqueous layer was extracted with DCM
7. customdried
8. filtrationfiltered
9. customevaporated
10. customThe crude product was purified by silica gel column chromatography
11. washeluting with a gradient of MeOH (1-5%) in DCM
12. additionProduct containing fractions
13. customevaporated
14. customdried