反应详情

To a well stirred suspension of 2-[(Cyclopropylmethyl-amino)-methyl]-3,5,7,8-tetrahydro-pyrano[4,3-d]pyrimidin-4-one (15.66 g, 57.6 mmol) in dichloromethane (600 mL) was added 2-(4-(4-methoxybenzoyl)piperidin-1-yl)acetic acid (16.45 g, 59.3 mmol), followed by triethylamine (24 mL, 173 mmol), 1H-benzo[d][1,2,3]triazol-1-ol hydrate (21.41 g, 140 mmol) and N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (13.26 g, 69.2 mmol). The resulting yellow suspension was stirred for 12 h, filtered and then washed with water three times (250 mL, 150 mL, then 50 mL). The organic layer was washed twice with brine (50 mL), dried with Na2SO4, filtered and concentrated in vacuo (33.34 g). The residue was dissolved in 750 mL dichloromethane, and washed with a pH 9 KHCO3/K2CO3 solution (2×100 mL). The organic layer was washed twice with brine (50 mL), dried with Na2SO4, filtered and concentrated in vacuo (23.4 g). The crude material was dissolved in approximately 25 mL MeOH resulting in an orange solution and placed in a freezer overnight to form a slurry. The mixture was filtered, washed with MeOH and dried in vacuo to yield 21.959 g of the title compound as a white solid. HRMS calculated for C27H34N4O5 495.2607. found (ESI, [M+H]+), 495.2607, retention time=3.717 min. CHN analysis: calculated (results). C, 65.57 (65.17), H, 6.93 (6.64), N, 11.33 (11.39).

1. stirringThe resulting yellow suspension was stirred for 12 h
2. filtrationfiltered
3. washwashed with water three times (250 mL, 150 mL
4. washThe organic layer was washed twice with brine (50 mL)
5. dry with materialdried with Na2SO4
6. filtrationfiltered
7. concentrationconcentrated in vacuo (33.34 g)
8. dissolutionThe residue was dissolved in 750 mL dichloromethane
9. washwashed with a pH 9 KHCO3/K2CO3 solution (2×100 mL)
10. washThe organic layer was washed twice with brine (50 mL)
11. dry with materialdried with Na2SO4
12. filtrationfiltered
13. concentrationconcentrated in vacuo (23.4 g)
14. dissolutionThe crude material was dissolved in approximately 25 mL MeOH resulting in an orange solution
15. customto form a slurry
16. filtrationThe mixture was filtered
17. washwashed with MeOH
18. customdried in vacuo