반응 #294

ord-3925d0a898bc49db9d7ff1cb2ec90b8d

반응 방정식

CC1c2ccc(Cl)nc2OC(C2CC2)CN1C
CC1c2ccc(Cl)nc2OC(C2
COc1nc(N)ccc1-c1cnn(C)c1
COc1nc(N)ccc1-c1cnn(
COc1nc(Nc2ccc3c(n2)OC(C2CC2)CN(C)C3C)ccc1-c1cnn(C)c1
COc1nc(Nc2ccc3c(n2)O
수율 15.3%

용매

반응 조건

온도
100°CELSIUS

실험 절차

8-chloro-2-cyclopropyl-4,5-dimethyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine (122 mg, 0.48 mmol), 6-methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-amine (99 mg, 0.48 mmol), Pd2dba3 (11.05 mg, 0.01 mmol), BINAP (15.03 mg, 0.02 mmol) and SODIUM TERT-BUTOXIDE (69.6 mg, 0.72 mmol) were weighed in to a microwave vial, the vial was capped and flushed with argon. toluene (4 mL) was added and the mixture was heated to 100°C in a microwaver apparatus for 2 h. The cooled reaction mixture was diluted with dichloromethane and filtered. The mixture was concentrated and purified by column chromatography on Silica, using gradient elution with increasing concentration of methanol, from 0 to 8 %, in dichloromethane to give a mixture of the two diastereomers. This was then subjected to diastereo and enantio separation to give 31 mg of isomer 1, 32.6 mg of isomer 2, 29 mg of isomer 3 and 29.7 mg of isomer 4 of 2-cyclopropyl-N-(6-methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)-4,5-dimethyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-8-amine (Total Yield 122.3 mg, 60 %).

출처

750 AstraZeneca ELN dataset