Reacción #1135843

Ecuación de reacción

N,O-Dimethylhydroxylamine-HCl

1H-indazole-3-carboxylic acid

carbonyldiimidazole

→

N-methoxy-N-methyl-1H-indazole-3-carboxamide

Rendimiento 79.0%

Disolventes

DMF

Condiciones de reacción

Tratamiento posterior

1. 1
   Otro(ca. 15 minutes)
2. 2
   Temperaturato cool to r.t
3. 3
   Temperaturathe mixture was heated to 65° C. for 3 hours
4. 4
   ConcentraciónThe reaction was concentrated to a paste
5. 5
   Lavadowashed subsequently with water and 2N HCl
6. 6
   FiltraciónThe solid was filtered
7. 7
   Lavadorinsed separately with EtOAc
8. 8
   LavadoThe EtOAc and DCM layers were separately washed with sodium bicarbonate
9. 9
   Secadodried over MgSO4
10. 10
    Concentraciónconcentrated under reduced pressure
11. 11
    Otrotriturated with 1:1 mixture of DCM-ether
12. 12
    Filtraciónfiltered
13. 13
    Otrodried

Procedimiento

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).

Fuente