1,1'-Carbonyldiimidazole → N-Methoxy-N-methyl-1H-indazole-3-carboxamide

Temperature

62.5 °C

1H-indazole-3-carboxylic acid (VIII) (100 g, 617 mmol) in DMF was treated with carbonyldiimidazole (110 g, 678 mmol) at r.t. until the evolution of gas ceased (ca. 15 minutes). The reaction was heated to 60-65° C. for two hours and then allowed to cool to r.t. N,O-Dimethylhydroxylamine-HCl (66.2 g, 678 mmol) was added as a solid and the mixture was heated to 65° C. for 3 hours, The reaction was concentrated to a paste and taken up in DCM, and washed subsequently with water and 2N HCl. The product could be seen coming out of solution. The solid was filtered and rinsed separately with EtOAc. The EtOAc and DCM layers were separately washed with sodium bicarbonate followed by brine, dried over MgSO4 and concentrated under reduced pressure. The resulting solids were combined, triturated with 1:1 mixture of DCM-ether, filtered, and dried to produce N-methoxy-N-methyl-1H-indazole-3-carboxamide (IX) as a white solid (100 g, 487 mmol, 79% yield). 1H NMR (DMSO-d6) δ ppm 3.46 (s, 3H), 3.69-3.85 (m, 3H), 7.13-7.31 (m, 1H), 7.41 (t, J=7.25 Hz, 1H), 7.56-7.65 (m, 1H), 7.93-8.08 (m, 1H); ESIMS found for C10H11N3O2 m/z 206 (M+H).

1. custom(ca. 15 minutes)
2. temperatureto cool to r.t
3. temperaturethe mixture was heated to 65° C. for 3 hours
4. concentrationThe reaction was concentrated to a paste
5. washwashed subsequently with water and 2N HCl
6. filtrationThe solid was filtered
7. washrinsed separately with EtOAc
8. washThe EtOAc and DCM layers were separately washed with sodium bicarbonate
9. dry with materialdried over MgSO4
10. concentrationconcentrated under reduced pressure
11. customtriturated with 1:1 mixture of DCM-ether
12. filtrationfiltered
13. customdried

ORD record

ord-6a42ea270f5841e1831eee3f156ef714

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08822478B2