反应详情

温度

70 °C

Ethyl1-[[(2-chloro-5-nitro-pyrimidin-4-yl)-cyclopentyl-amino]methyl]cyclopropane-1-carboxylate (Intermediate 132; 35.92 g, 97.4 mmol) was dissolved in the acetic acid (750 mL) and the solution stirred and heated to 70° C. under nitrogen. Iron powder (14.61 g) was added in portions over 10 minutes. Over the next 10-15 minutes the resulting exotherm took the reaction mixture temperature up to a maximum of 92° C. The temperature then slowly dropped back to 75° C. The dark reaction mixture was then stirred at 75° C. for 3 hours. The reaction mixture was filtered whilst still hot through a bed of celite and the bed washed through with DCM. The acetic acid/DCM filtrate was evaporated to dryness and the resulting residue azeotroped three times with toluene. The residue was left under high vacuum at room temperature overnight, taken up in DCM and filtered through a small bed of celite. The celite was washed with DCM and the filtrate concentrated down to 250 mL and loaded onto a dry silica column pre-conditioned with DCM. The column was eluted with a 5-10% gradient of 7N NH3/MeOH in DCM and product containing fractions were combined and evaporated. The resultant material was recrystallised from isopropanol. The solid precipitate was collected by filtration, washed with chilled isopropanol and dried by desiccation under high vacuum at room temperature to constant weight to yield the title compound as a grey solid (17.1 g.

1. customOver the next 10-15 minutes
2. customup to a maximum of 92° C
3. additionThe temperature then slowly dropped back to 75° C
4. customThe dark reaction mixture
5. stirringwas then stirred at 75° C. for 3 hours
6. filtrationThe reaction mixture was filtered whilst still hot through a bed of celite
7. washthe bed washed through with DCM
8. customThe acetic acid/DCM filtrate was evaporated to dryness
9. customthe resulting residue azeotroped three times with toluene
10. filtrationfiltered through a small bed of celite
11. washThe celite was washed with DCM
12. concentrationthe filtrate concentrated down to 250 mL
13. washThe column was eluted with a 5-10% gradient of 7N NH3/MeOH in DCM and product
14. additioncontaining fractions
15. customevaporated
16. customThe resultant material was recrystallised from isopropanol
17. filtrationThe solid precipitate was collected by filtration
18. washwashed with chilled isopropanol
19. customdried by desiccation under high vacuum at room temperature to constant weight