反应详情

A mixture of 1-[(4-amino-2-propyl-1H-imidazo[4,5-c][1,5]napthyridin-1-yl)methyl]cyclopentanol (511 mg), platinum oxide (511 mg), and trifluoroacetic acid was placed under hydrogen pressure (50 psi, 3.4×105 Pa) overnight on a Parr apparatus. The mixture was filtered through a layer of CELITE filter aid and the filter cake was rinsed with methanol. The filtrate was concentrated under reduced pressure. The residue was combined with concentrated hydrochloric acid (2 mL) and stirred at ambient temperature for 2 hours. The mixture was diluted with water (10 mL) and then cooled to 0° C. The pH was adjusted to 12 with 6N sodium hydroxide and then the mixture was extracted with dichloromethane (3×50 mL). The combined organics were washed with brine (20 mL), dried over sodium sulfate, filtered, and then concentrated under reduced pressure. The residue was triturated with acetonitrile, purified by HPFC eluting with a gradient of 0-35% CMA in chloroform, and then triturated with acetonitrile to provide 167 mg of 1-[(4-amino-2-propyl-6,7,8,9-tetrahydro-1H-imidazo[4,5-c][1,5]napthyridin-1-yl)methyl]cyclopentanol as a white powder, mp 207.0-208.0° C. Anal. Calcd for C18H27N5O.0.25H2O C, 64.74; H, 8.30; N, 20.97. Found: C, 64.71; H, 8.29; N, 20.98.

1. custompressure (50 psi, 3.4×105 Pa) overnight
2. filtrationThe mixture was filtered through a layer of CELITE
3. filtrationfilter aid
4. washthe filter cake was rinsed with methanol
5. concentrationThe filtrate was concentrated under reduced pressure
6. additionThe mixture was diluted with water (10 mL)
7. temperaturecooled to 0° C
8. extractionthe mixture was extracted with dichloromethane (3×50 mL)
9. washThe combined organics were washed with brine (20 mL)
10. dry with materialdried over sodium sulfate
11. filtrationfiltered
12. concentrationconcentrated under reduced pressure
13. customThe residue was triturated with acetonitrile
14. custompurified by HPFC
15. washeluting with a gradient of 0-35% CMA in chloroform
16. customtriturated with acetonitrile