反応 #1135843

反応方程式

N,O-Dimethylhydroxylamine-HCl

1H-indazole-3-carboxylic acid

carbonyldiimidazole

→

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

収率 79.0%

溶媒

DMF

反応条件

後処理

1. 1
   その他(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
   濃縮The reaction was concentrated to a paste
5. 5
   洗浄washed subsequently with water and 2N HCl
6. 6
   ろ過The solid was filtered
7. 7
   洗浄rinsed separately with EtOAc
8. 8
   洗浄The EtOAc and DCM layers were separately washed with sodium bicarbonate
9. 9
   乾燥dried over MgSO4
10. 10
    濃縮concentrated under reduced pressure
11. 11
    その他triturated with 1:1 mixture of DCM-ether
12. 12
    ろ過filtered
13. 13
    その他dried

実験手順

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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