Sodium hydride → HCID 67352869, compound

HRID 1478899Notes

Reaction equation

HRID 1478899 reaction equation
[NH:1]1[C:9]2[CH:8]=[C:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[N:6]=[CH:5][C:4]=2[CH:3]=[CH:2]1.[H-].[Na+].Br[CH2:20][CH:21]1[CH2:23][CH2:22]1>CN(C=O)C>[CH:21]1([CH2:20][N:1]2[C:9]3[CH:8]=[C:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[N:6]=[CH:5][C:4]=3[CH:3]=[CH:2]2)[CH2:23][CH2:22]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 81503BromomethylcyclopropaneHCID 57763153HCID 57763153, compound

Product 1

HCID 67352869HCID 67352869, compoundYield 88%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of tert-butyl 1H-pyrrolo[3,2-c]pyridine-6-carboxylate (1.0 g, 4.6 mmol) in DMF (20 ml) was added sodium hydride (60% in oil) (0.4 g, 10 mmol) and stirred at room temperature for 3 h. To the mixture, (bromomethyl)cyclopropane (1.2 g, 9.2 mmol) was added and stirred at room temperature. for 2 h. The reaction mixture was extracted with EtOAc/H2O. The organic layer was washed with brine, dried over MgSO4 and concentrated in vacuo. The crude mixture was purified by chromatography (SiO2, hexanes:EtOAc=50:50) to give tert-butyl 1-(cyclopropylmethyl)-1H-pyrrolo[3,2-c]pyridine-6-carboxylate (2A, 1.1 g, 4.0 mmol, 88% yield) as a yellow oil. 1 H NMR (400 MHz, CHLOROFORM-d) δ ppm 0.16-0.23 (m, 2 H) 0.44-0.51 (m, 2 H) 0.99-1.11 (m, 1H) 1.48 (s, 9 H) 3.84 (d, J=7.07 Hz, 2 H) 6.45-6.47 (m, 1 H) 7.19 (d, J=3.03 Hz, 1 H) 7.96 (s, 1 H) 8.79 (s, 1 H).

Workup

  1. stirringstirred at room temperature
  2. waitfor 2 h
  3. extractionThe reaction mixture was extracted with EtOAc/H2O
  4. washThe organic layer was washed with brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customThe crude mixture was purified by chromatography (SiO2, hexanes:EtOAc=50:50)

Sources & evidence

ORD record
ord-2f31a264a65843948ec5ce9078064c75
Source dataset
uspto-grants-2016_08
Patent number
US09403819B2

Reaction notes

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