Ammonia → Tiazofurin

Ethyl 2-β-D-ribofuranosylthiazole-4-carboxylate (5, 120.8 g, 0.418 mol) was mixed with cold (-20° C.) methanolic ammonia (saturated at 0° C.). The mixture was protected from moisture and at 5° C. for 2 days. The mixture was evaporated (40° C., 20 mm) to a sticky foam. The residue was dissolved in hot ethanol (500 mL) and then, with stirring, 2-propanol (500 mL) was added. The mixture was allowed to stand at ambient temperature for 2 h and then was refrigerated (5° C.) for 1 d. The yellow solid was collected by filtration, washed with 2-propanol (2×100 mL) and dried (25° C., 20 mm); 98.0 g, mp 139-142° C. The washes were combined with the filtrate and the solution was evaporated (40° C., 20 mm) to dryness. The residue was dissolved in hot ethanol (100 mL). The solution was allowed to stand at ambient temperature until crystallization began and then was stored at 5° C. for 1 d. The solid was collected by filtration, washed with ethanol (2×25 mL), and dried (25° C., 20 mm); 6.9 g, mp 138-139° C. The two crops of solid (104.9 g, 0.403 mol, 96%) were combined and dissolved in boiling ethanol (1.1 L). Norit A (10 g) was added and the mixture was stirred and boiled for 5 min. The mixture was filtered through an ertel pad and pad was washed with hot ethanol (3×100 ml). The washes were combined with the filtrate; the solution was stirred rapidly and cooled in ice bath for 1 h. The mixture was refrigerated (5° C.) for 3 d. The solid was collected by filtration, washed with ethanol (2×100 mL), and dried (50° C., 1 mm) for 1 d; 91.1 g (0.35 mol, 84%), mp 140-142° C. The combined filtrate and washes was concentrated to a volume of approx. 350 mL. The solution was heated to boiling and 2-propanol (200 mL) was added. The solution was concentrated to a volume of 300 mL and then refrigerated (5° C.) for 1 d. The solid was collected by filtration, washed with 2-propanol (3×25 mL), and dried (50° C., 1 mm); 9.4 g (0.036 mol, 8%), mp 138-139° C. The crops were not combined. 1H NMR (DMSO-d6): δ3.59 (m, 2), 3.89 (s, 2), 4.07 (t, 1), 4.85 (t, 1), 4.93 (d, 1), 5.06 (d, 1), 5.36 (d, 1), 7.55 (s, 1), 7.70 (s, 1) and 8.21 (s, 1).

1. customat 5° C.
2. customfor 2 days
3. customThe mixture was evaporated (40° C., 20 mm) to a sticky foam
4. dissolutionThe residue was dissolved in hot ethanol (500 mL)
5. addition2-propanol (500 mL) was added
6. custom(5° C.)
7. customfor 1 d
8. filtrationThe yellow solid was collected by filtration
9. washwashed with 2-propanol (2×100 mL)
10. customdried (25° C., 20 mm)
11. customthe solution was evaporated (40° C., 20 mm) to dryness
12. dissolutionThe residue was dissolved in hot ethanol (100 mL)
13. customto stand at ambient temperature until crystallization
14. waitwas stored at 5° C. for 1 d
15. filtrationThe solid was collected by filtration
16. washwashed with ethanol (2×25 mL)
17. customdried (25° C., 20 mm)
18. dissolutiondissolved
19. stirringthe mixture was stirred
20. waitboiled for 5 min
21. filtrationThe mixture was filtered through an ertel pad and pad
22. washwas washed with hot ethanol (3×100 ml)
23. stirringthe solution was stirred rapidly
24. temperaturecooled in ice bath for 1 h
25. custom(5° C.)
26. customfor 3 d
27. filtrationThe solid was collected by filtration
28. washwashed with ethanol (2×100 mL)
29. customdried (50° C., 1 mm) for 1 d
30. concentrationThe combined filtrate and washes was concentrated to a volume of approx. 350 mL
31. temperatureThe solution was heated
32. addition2-propanol (200 mL) was added
33. concentrationThe solution was concentrated to a volume of 300 mL
34. custom(5° C.)
35. customfor 1 d
36. filtrationThe solid was collected by filtration
37. washwashed with 2-propanol (3×25 mL)
38. customdried (50° C., 1 mm)

ORD record

ord-7487bf231e514213a8bffcefa647afd0

Source dataset

uspto-grants-1999_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05907036