反应详情

温度

70 °C

Tert-butyl (3-{4-[5-amino-6-(pyridin-3-ylcarbamoyl)pyrazin-2-yl]phenyl}propyl)(3-methoxypropyl)carbamate (1 kg) and water (8 L) were added to the reactor, stirred and heated up to 70° C. 36% Hydrochloric acid (606 ml) was added slowly controlling rate of gas evolution. The contents were stirred for 45 minutes at 70° C. The pH was adjusted to 3-4 by addition of sodium hydroxide (325 ml). The contents were cooled to 50° C. and 2-methyltetrahydrofuran (5 L) was added. The pH was then adjusted to pH 11-12 by the addition of 48% sodium hydroxide liquor (170 ml). The contents were then cooled to 40° C. The batch allowed to settle and the two layers separated. The aqueous layer was washed with 2-methyltetrahydrofuran (2.5 L). The combined organic layers were washed with a solution of 10% w/v aqueous sodium chloride solution. The organic layer was distilled to remove 3.75 L of distillate. The remaining liquors were heated to 50° C. and methyl-t-butyl ether (4 L) added. The liquors were cooled to 10° C. over 4 hours then isolated by filtration. The solid was washed with methyl-t-butyl ether (2 L×2) and dried in a vacuum oven at 50° C. 3-amino-6-(4-{3-[(3-methoxypropyl)amino]propyl}phenyl)-N-pyridin-3-ylpyrazine-2-carboxamide (721 g).

1. stirringThe contents were stirred for 45 minutes at 70° C
2. temperatureThe contents were cooled to 50° C.
3. temperatureThe contents were then cooled to 40° C
4. customthe two layers separated
5. washThe aqueous layer was washed with 2-methyltetrahydrofuran (2.5 L)
6. washThe combined organic layers were washed with a solution of 10%
7. distillationThe organic layer was distilled
8. customto remove 3.75 L of distillate
9. temperatureThe remaining liquors were heated to 50° C.
10. additionmethyl-t-butyl ether (4 L) added
11. temperatureThe liquors were cooled to 10° C. over 4 hours
12. customthen isolated by filtration
13. washThe solid was washed with methyl-t-butyl ether (2 L×2)
14. customdried in a vacuum oven at 50° C