Reaktion #156100

Reaktionsgleichung

N,O-Dimethylhydroxylamine-HCl

1H-indazole-3-carboxylic acid

carbonyldiimidazole

→

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

Ausbeute 79.0%

Lösungsmittel

DMF

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstige(ca. 15 minutes)
2. 2
   Temperaturto cool to r.t
3. 3
   Temperaturthe mixture was heated to 65° C. for 3 hours
4. 4
   EinengenThe reaction was concentrated to a paste
5. 5
   Waschenwashed subsequently with water and 2N HCl
6. 6
   FiltrationThe solid was filtered
7. 7
   Waschenrinsed separately with EtOAc
8. 8
   WaschenThe EtOAc and DCM layers were separately washed with sodium bicarbonate
9. 9
   Trocknendried over MgSO4
10. 10
    Einengenconcentrated under reduced pressure
11. 11
    Sonstigetriturated with 1:1 mixture of DCM-ether
12. 12
    Filtrationfiltered
13. 13
    Sonstigedried

Vorschrift

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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