Methyl iodide → Methyl 1-(1-methylethyl)-6-nitro-1H-indazole-4-carboxylate

HRID 1476476Notes

Reaction equation

HRID 1476476 reaction equation
[H-].[Na+].[N+:3]([C:6]1[CH:7]=[C:8]([C:15]([O:17][CH3:18])=[O:16])[C:9]2[CH:10]=[N:11][NH:12][C:13]=2[CH:14]=1)([O-:5])=[O:4].Br[CH:20]([CH3:22])[CH3:21].IC>CS(C)=O.CN(C)C=O>[CH3:21][CH:20]([N:12]1[C:13]2[CH:14]=[C:6]([N+:3]([O-:5])=[O:4])[CH:7]=[C:8]([C:15]([O:17][CH3:18])=[O:16])[C:9]=2[CH:10]=[N:11]1)[CH3:22]

Participants

7

Reactant 4

HCID 6328Methyl iodideHCID 63582-BromopropaneHCID 24758Sodium hydrideHCID 24728069Methyl 6-nitro-1H-indazole-4-carboxylate

Product 1

HCID 67468642Methyl 1-(1-methylethyl)-6-nitro-1H-indazole-4-carboxylate

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (1.142 g, 45.2 mmol) was added to N,N-Dimethylformamide (DMF) (100 mL) which was cooled in a ice water bath. A DMSO solution (20 mL) of methyl 6-nitro-1H-indazole-4-carboxylate (5 g, 22.61 mmol) was then added dropwise. After 15 minutes was added 2-bromopropane (4.25 mL, 45.2 mmol) dropwise and the contents were stirred at room temperature for 16 hours. Next added iodomethane (2.83 mL, 45.2 mmol) and let stir at room temperature for 3 hours followed by heating at 50° C. for 3 hours. The solvent was removed in vacuo. The residue was purified via silica gel chromatography (eluent: 0% to 25% EtOAc:Hex) to afford the product as 1.39 g (23%). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 4.07 (s, 3H), 8.61-8.63 (m, 1H), 8.64 (s, 1H), 8.73 (d, J=2.02 Hz, 1H); LCMS (ES) [M+H]+ 264.0

Workup

  1. temperaturewas cooled in a ice water bath
  2. stirringlet stir at room temperature for 3 hours
  3. temperatureby heating at 50° C. for 3 hours
  4. customThe solvent was removed in vacuo
  5. customThe residue was purified via silica gel chromatography (eluent: 0% to 25% EtOAc:Hex)
  6. customto afford the product as 1.39 g (23%)

Sources & evidence

ORD record
ord-0faa9cf1658b4fccafa767823b30c80c
Source dataset
uspto-grants-2015_04
Patent number
US09018382B2

Reaction notes

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