反应详情

2-Piperidin-1-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ol. To solution of KOtBu (1.3 g, 5.77 mmol) in tBuOH (32 mL) was added 5-oxo-1-(3-trifluoromethyl-pyridin-2-yl)-azepane-4-carboxylic acid ethyl ester (Intermediate B; 1.27 g, 3.85 mmol), followed by piperidine-1-carboximidamide hydrobromide (1.2 g, 5.77 mmol). After heating at reflux for 24 h, the mixture was cooled and concentrated. The residue was dissolved in water and CH2Cl2. The aqueous layer was acidified to pH=7 with HOAc. The layers were separated and the aqueous layer was extracted with CH2Cl2. The combined organic layers were dried (Na2SO4) and concentrated. The residue was triturated with Et2O and filtered. The filtrate was concentrated and the residue was purified (FCC) to give the title compound (776.4 g, 51%—combined filtered and chromatographed).

1. temperatureAfter heating
2. temperatureat reflux for 24 h
3. temperaturethe mixture was cooled
4. concentrationconcentrated
5. dissolutionThe residue was dissolved in water
6. customThe layers were separated
7. extractionthe aqueous layer was extracted with CH2Cl2
8. dry with materialThe combined organic layers were dried (Na2SO4)
9. concentrationconcentrated
10. customThe residue was triturated with Et2O
11. filtrationfiltered
12. concentrationThe filtrate was concentrated
13. customthe residue was purified (FCC)