反应详情

6-(6-methoxypyridin-3-ylamino)-5-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)nicotinaldehyde (157 mg, 0.352 mmol) was dissolved in methanol (5.0 mL) and sodium borohydride (21.6 mg, 0.571 mmol) was added. The reaction was stirred at room temperature for 75 minutes, and then more NaBH4 (26 mg, 0.69 mmol) was added, along with DCM (3 mL). After 40 more minutes, 5 N aqueous HCl (0.50 mL, 2.5 mmol) was added, along with a MeOH rinse (about 1 mL), and stirring was continued at room temperature overnight. Then, the reaction was diluted with water (20 mL), and the suspension was filtered. The filtration was sluggish, so the filtrate was discarded, and the solid was collected, and the unfiltered material was extracted with 10:1 DCM/MeOH. These organic extracts were combined with the solid that was collected, while the aqueous suspension was again filtered. The solid from this filtration was combined with the solid and organic extracts collected earlier. The resultant solution was concentrated, treated with EtOAc, and filtered. The solid was washed with EtOAc and MeOH, but the solid was not 95% pure by HPLC, so the filtrate and solid were collected, concentrated, treated with DCM, and filtered again. The solid was washed with DCM. The product was still not 95% pure by HPLC, so the filtrate and solid were again collected, concentrated, and this time purified on HPLC (10% to 100% MeCN/water with 0.1% TFA over 30 minutes with a total flow rate of 100 mL/min) to give (6-(6-methoxypyridin-3-ylamino)-5-(2-methyl-9H-purin-6-yl)pyridin-3-yl)methanol (91.1 mg, 71% yield). MS (ESI pos. ion) m/z 364 (M+H)+. 1H NMR (d6-DMSO, 400 MHz) δ 12.62 (s, 1H), 9.79 (s, 1H), 8.62 (s, 1H), 8.54 (s, 1H), 8.24 (s, 1H), 8.17 (d, J=8.41 Hz, 1H), 6.86 (d, J=8.61 Hz, 1H), 4.52 (s, 2H), 3.85 (s, 3H), 2.86 (s, 3H).

1. washrinse (about 1 mL)
2. stirringstirring
3. waitwas continued at room temperature overnight
4. additionThen, the reaction was diluted with water (20 mL)
5. filtrationthe suspension was filtered
6. filtrationThe filtration
7. customthe solid was collected
8. extractionthe unfiltered material was extracted with 10:1 DCM/MeOH
9. customthat was collected, while the aqueous suspension
10. filtrationwas again filtered
11. filtrationThe solid from this filtration
12. customcollected earlier
13. concentrationThe resultant solution was concentrated
14. additiontreated with EtOAc
15. filtrationfiltered
16. washThe solid was washed with EtOAc and MeOH
17. customso the filtrate and solid were collected
18. concentrationconcentrated
19. additiontreated with DCM
20. filtrationfiltered again
21. washThe solid was washed with DCM
22. customso the filtrate and solid were again collected
23. concentrationconcentrated
24. customthis time purified on HPLC (10% to 100% MeCN/water with 0.1% TFA over 30 minutes with a total flow rate of 100 mL/min)