反应详情

温度

80 °C

A dichloromethane solution (3 ml) of bis-(4-methoxy-benzyl)-[5-(2-morpholin-4-yl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl)-pyrimidin-2-yl]-amine (100 mg, 0.185 mmol), pyridine (30 μl, 0.37 mmol) and thiophosgene (28 μl, 0.37 mmol) was stirred for 40 minutes. This was concentrated and dried under reduced pressure, and subsequently (4-ethyl-piperazin-1-yl)-(3-amino-4-methyl-phenyl)-methanone (90 mg, 0.390 mmol) obtained in Step B was added, followed by stirring in dichloromethane (3 ml) for 16 hours. The reaction mixture was washed with aqueous ammonium chloride solution, and subsequently dried over sodium sulfate. The drying agent was removed, followed by concentration and drying. To this, TFA (2 ml) was added, followed by stirring at 80° C. for 4 hours. After TFA was removed under reduced pressure, dichloromethane was added, followed by washing with sodium hydrogencarbonate aqueous solution. The organic layer was dried over sodium sulfate, filtered and concentrated, to obtain a crude product. Purification by silica gel column chromatography (dichloromethane/methanol=10/1) afforded 4-(2-amino-pyrimidin-5-yl)-2-morpholin-4-yl-5,6-dihydro-pyrrolo[2,3-d]pyrimidine-7-carbothioic acid [5-(4-ethyl-piperazine-1-carbonyl)-2-methyl-phenyl]-amide (42 mg, 39%) as a pale yellow powder.

1. concentrationThis was concentrated
2. additionwas added
3. washThe reaction mixture was washed with aqueous ammonium chloride solution
4. dry with materialsubsequently dried over sodium sulfate
5. customThe drying agent was removed
6. concentrationfollowed by concentration
7. customdrying
8. additionTo this, TFA (2 ml) was added
9. customAfter TFA was removed under reduced pressure, dichloromethane
10. additionwas added
11. washby washing with sodium hydrogencarbonate aqueous solution
12. dry with materialThe organic layer was dried over sodium sulfate
13. filtrationfiltered
14. concentrationconcentrated
15. customto obtain a crude product
16. customPurification by silica gel column chromatography (dichloromethane/methanol=10/1)