反应 #1135843

反应方程式

N,O-Dimethylhydroxylamine-HCl

1H-indazole-3-carboxylic acid

carbonyldiimidazole

→

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

收率 79.0%

溶剂

DMF

反应条件

后处理

1. 1
   其他(ca. 15 minutes)
2. 2
   温度to cool to r.t
3. 3
   温度the mixture was heated to 65° C. for 3 hours
4. 4
   浓缩The reaction was concentrated to a paste
5. 5
   洗涤washed subsequently with water and 2N HCl
6. 6
   过滤The solid was filtered
7. 7
   洗涤rinsed separately with EtOAc
8. 8
   洗涤The EtOAc and DCM layers were separately washed with sodium bicarbonate
9. 9
   干燥dried over MgSO4
10. 10
    浓缩concentrated under reduced pressure
11. 11
    其他triturated with 1:1 mixture of DCM-ether
12. 12
    过滤filtered
13. 13
    其他dried

实验过程

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).

来源