反应详情

A solution of 5-benzyl-1H-tetrazole (1.0 g, 6.24 mmol) in MeOH (5 ml) was treated with 1-chloro-3-iodopropane (1.0 ml, 9.36 mmol) and a solution of 0.5M NaOMe in MeOH (4.7 ml, 9.36 mmol). The reaction was heated at reflux for 18 h then partitioned between 2M HCl (aq) and EtOAc. The organic layer was separated and the aqueous layer extracted once more with EtOAc. The combined extracts were washed with brine, dried (MgSO4) and concentrated, giving a yellow solid. (796 mg). 700 mg of this material was reacted with 8-chloro-3-pentyl-7-(2-propen-1-yl)-3,7-dihydro-1H-purine-2,6-dione (732 mg, 2.47 mmol) and Cs2CO3 (967 mg, 3.0 mmol) in DMF (20 ml) at 75° C. for 24 h. The reaction was allowed to cool to rt and the mixture was degassed by applying a vacuum and then nitrogen was introduced. Pd(PPh3)4 (428 mg, 0.37 mmol) was added and the mixture degassed once more. Morpholine (2.1 ml, 24.7 mmol) was added and the mixture was stirred under nitrogen for 3 h, then partitioned between 2M HCl (aq) and EtOAc. The organic layer was separated and the aqueous layer extracted once more. The combined extracts were concentrated, giving a yellow residue. MeOH was added and then passed down an aminopropyl SPE, the product eluting with 2-3% AcOH/MeOH. The product fractions were combined and concentrated then purified by the MDAP to give the title compound as a white solid (35 mg, 3%).

1. temperatureThe reaction was heated
2. temperatureat reflux for 18 h
3. customthen partitioned between 2M HCl (aq) and EtOAc
4. customThe organic layer was separated
5. extractionthe aqueous layer extracted once more with EtOAc
6. washThe combined extracts were washed with brine
7. dry with materialdried (MgSO4)
8. concentrationconcentrated
9. customgiving a yellow solid
10. customthe mixture was degassed
11. additionnitrogen was introduced
12. customthe mixture degassed once more
13. custompartitioned between 2M HCl (aq) and EtOAc
14. customThe organic layer was separated
15. extractionthe aqueous layer extracted once more
16. concentrationThe combined extracts were concentrated
17. customgiving a yellow residue
18. washthe product eluting with 2-3% AcOH/MeOH
19. concentrationconcentrated
20. customthen purified by the MDAP