반응 #1135843

반응 방정식

N,O-Dimethylhydroxylamine-HCl

1H-indazole-3-carboxylic acid

carbonyldiimidazole

→

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

수율 79.0%

용매

DMF

반응 조건

후처리

1. 1
   기타(ca. 15 minutes)
2. 2
   온도to cool to r.t
3. 3
   온도the mixture was heated to 65° C. for 3 hours
4. 4
   농축The reaction was concentrated to a paste
5. 5
   세척washed subsequently with water and 2N HCl
6. 6
   여과The solid was filtered
7. 7
   세척rinsed separately with EtOAc
8. 8
   세척The EtOAc and DCM layers were separately washed with sodium bicarbonate
9. 9
   건조dried over MgSO4
10. 10
    농축concentrated under reduced pressure
11. 11
    기타triturated with 1:1 mixture of DCM-ether
12. 12
    여과filtered
13. 13
    기타dried

실험 절차

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).

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