Hydrochloric Acid → HCID 59187379, compound

Temperature

185 °C

To a solution of 2,3-dichloropyrazine (8-1, 3.5 g, 23.5 mmol) in MeOH (115 mL) was added NaOMe in methanol (15.0 mL, 70.5 mmol, 4.37M) and the system was stirred overnight. The reaction contents were then filtered through a fritted funnel of medium porosity, concentrated, and partitioned between EtOAc and water. The organic phase was washed with brine, dried over Na2SO4, filtered and concentrated to afford a clear oil. To this clear oil (2.5 g, 17.8 mmol) in DMF (17 ml) at 0° C. was added NBS (3.5 g, 19.6 mmol) the system was stirred overnight. The system was quenched with Na2SO3 and then poured into ice water. The resulting solids that precipitated from solution were isolated by filtration and dried to afford a white solid. To this white solid (1 g, 4.5 mmol) in DMF (9 mL) was added copper cyanide (0.45 g, 5.0 mmol) and heated to 185° C. for 20 minutes in the microwave reactor. The mixture was cooled and partitioned between EtOAc and water. The organic phase was washed with brine, dried over Na2SO4, filtered and concentrated. The crude material was purified by gradient elution on silica (0 to 65% EtOAc in hexanes) to afford a white powder. To this white powder (0.740 g, 4.5 mmol) in MeOH (40 mL) was added Pearlman's catalyst (0.315 g, 0.45 mmol, 20 weight percent) and concentrated HCl (3.0 mL, 36 mmol, 12M). The system was then stirred under an atmosphere of hydrogen via a balloon for 1.5 h. The reaction contents were filtered through a pad of celite followed by removal of methanol in vacuo. The crude mixture was then dissolved in DCM, basified using saturated Na2CO3 and then extracted several times with DCM. The organic phase was washed with brine, dried over Na2SO4, filtered and concentrated to yield the desired product (8-2) as a bone solid. ESI+MS [M+H]+ C7H11N3O2: M-16 (—NH2), 152.8 found, 152.2 required.

1. customThe reaction contents
2. filtrationwere then filtered through a fritted funnel of medium porosity
3. concentrationconcentrated
4. custompartitioned between EtOAc and water
5. washThe organic phase was washed with brine
6. dry with materialdried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated
9. customto afford a clear oil
10. stirringwas stirred overnight
11. customThe system was quenched with Na2SO3
12. additionpoured into ice water
13. customThe resulting solids that precipitated from solution
14. customwere isolated by filtration
15. customdried
16. customto afford a white solid
17. temperatureThe mixture was cooled
18. custompartitioned between EtOAc and water
19. washThe organic phase was washed with brine
20. dry with materialdried over Na2SO4
21. filtrationfiltered
22. concentrationconcentrated
23. customThe crude material was purified by gradient elution on silica (0 to 65% EtOAc in hexanes)
24. customto afford a white powder
25. stirringThe system was then stirred under an atmosphere of hydrogen via a balloon for 1.5 h
26. customThe reaction contents
27. filtrationwere filtered through a pad of celite
28. customfollowed by removal of methanol in vacuo
29. dissolutionThe crude mixture was then dissolved in DCM
30. extractionextracted several times with DCM
31. washThe organic phase was washed with brine
32. dry with materialdried over Na2SO4
33. filtrationfiltered
34. concentrationconcentrated

ORD record

ord-20891b178b2b4478820cb368e9702c7d

Source dataset

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08349872B2