Methyl iodide → tert-Butyl 4-(6-bromo-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-1H-pyrazole-1-carboxylate

HRID 2205867Notes

Reaction equation

HRID 2205867 reaction equation
[H-].[Na+].[Br:3][C:4]1[N:9]=[CH:8][C:7]2[CH:10]=[C:11]([C:13]3[CH:14]=[N:15][N:16]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH:17]=3)[NH:12][C:6]=2[CH:5]=1.I[CH3:26]>CN(C=O)C.O.CCOC(C)=O>[Br:3][C:4]1[N:9]=[CH:8][C:7]2[CH:10]=[C:11]([C:13]3[CH:14]=[N:15][N:16]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH:17]=3)[N:12]([CH3:26])[C:6]=2[CH:5]=1

Participants

7

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 86706280tert-Butyl 4-(6-bromo-1H-pyrrolo[3,2-c]pyridin-2-yl)-1H-pyrazole-1-carboxylate

Product 1

HCID 86706281tert-Butyl 4-(6-bromo-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-1H-pyrazole-1-carboxylateYield 78.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Sodium hydride (60% in mineral oil, 7.1 mg, 0.178 mmol) was added to a solution of tert-butyl 4-(6-bromo-1H-pyrrolo[3,2-c]pyridin-2-yl)-1H-pyrazole-1-carboxylate (27) (43 mg, 0.118 mmol) in DMF (515 μL) at 0° C. The reaction mixture was then stirred for 30 min at 0° C. before the addition of iodomethane (18 μL, 0.237 mmol). After stirring for 30 min, it was diluted with water and EtOAc. The layers were separated and the aqueous layer was extracted with EtOAc. The combined organic layers were dried (MgSO4), filtered and concentrated under reduced pressure. The crude was purified via Biotage (DCM/EtOAc 99/1 to 90/10; 12+M column) to afford the title compound as a white solid (35 mg, 78%). 1H NMR (500 MHz, CDCl3) 1.71 (s, 9H), 3.78 (s, 1H), 6.68 (d, J=0.6 Hz, 1H), 7.46 (m, 1H), 7.94 (d, J=0.6 Hz, 1H), 8.32 (d, J=0.6 Hz, 1H), 8.64 (s, 1H).

Workup

  1. customThe layers were separated
  2. extractionthe aqueous layer was extracted with EtOAc
  3. dry with materialThe combined organic layers were dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe crude was purified via Biotage (DCM/EtOAc 99/1 to 90/10; 12+M column)

Sources & evidence

ORD record
ord-de82d57a2f564204a6f01c931e0696eb
Source dataset
uspto-grants-2016_06
Patent number
US09371319B2

Reaction notes

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