4-Hydroxymethylpyridine → 3-bromo-1-methyl-6-(pyridin-4-ylmethoxy)-1H-pyrrolo[2,3-b]pyridine

HRID 1622878Notes

Reaction equation

HRID 1622878 reaction equation
[Br:1][C:2]1[C:10]2[C:5](=[N:6][C:7](F)=[CH:8][CH:9]=2)[N:4]([CH3:12])[CH:3]=1.[N:13]1[CH:18]=[CH:17][C:16]([CH2:19][OH:20])=[CH:15][CH:14]=1.[H-].[Na+]>CN(C=O)C>[Br:1][C:2]1[C:10]2[C:5](=[N:6][C:7]([O:20][CH2:19][C:16]3[CH:17]=[CH:18][N:13]=[CH:14][CH:15]=3)=[CH:8][CH:9]=2)[N:4]([CH3:12])[CH:3]=1

Participants

5

Reactant 3

HCID 114724-HydroxymethylpyridineHCID 24758Sodium hydrideHCID 678140183-bromo-6-fluoro-1-methyl-1H-pyrrolo[2,3-b]pyridine

Product 1

HCID 678158433-bromo-1-methyl-6-(pyridin-4-ylmethoxy)-1H-pyrrolo[2,3-b]pyridineYield 54.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 3-bromo-6-fluoro-1-methyl-1H-pyrrolo[2,3-b]pyridine (0.4 g, 1.74 mmol) and pyridine-4-ylmethanol (0.21 g, 1.93 mmol) in DMF (5.0 mL) is added portionwise sodium hydride (0.05 g, 2.11 mmol) at room temperature and the resulting reaction mixture is stirred for 1 h. The reaction is quenched with cold brine solution and extracted with EtOAc (4×100 mL). The combined organic layers are dried over sodium sulphate, filtered and concentrated in vacuo. The residue is purified by crystallization from Et2O/pentane to give the title compound (0.300 g, 0.942 mmol) as an orange-red solid. MS (m/z): 318, 320 (M+1). 1H-NMR (400 MHz, DMSO-d6): δ 3.73 (s, 3H), 5.48 (s, 2H), 6.76 (d, 1H), 7.47 (d, 2H), 7.50 (s, 1H), 7.78 (d, 1H), 8.56 (d, 2H).

Workup

  1. customthe resulting reaction mixture
  2. customThe reaction is quenched with cold brine solution
  3. extractionextracted with EtOAc (4×100 mL)
  4. dry with materialThe combined organic layers are dried over sodium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue is purified by crystallization from Et2O/pentane

Sources & evidence

ORD record
ord-04f4ce9ecf48476dad32a603143d6e70
Source dataset
uspto-grants-2014_07
Patent number
US08778946B2

Reaction notes

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