Water → 6-((6-bromo-3H-imidazo[4,5-b]pyridin-3-yl)methyl)-2-(methylthio)benzo[d]oxazole

HRID 1848129Notes

Reaction equation

HRID 1848129 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[N:10]=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.[H-].[Na+].Cl[CH2:14][C:15]1[CH:25]=[CH:24][C:18]2[N:19]=[C:20]([S:22][CH3:23])[O:21][C:17]=2[CH:16]=1.O>CN(C=O)C>[Br:1][C:2]1[CH:3]=[C:4]2[N:10]=[CH:9][N:8]([CH2:14][C:15]3[CH:25]=[CH:24][C:18]4[N:19]=[C:20]([S:22][CH3:23])[O:21][C:17]=4[CH:16]=3)[C:5]2=[N:6][CH:7]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 9115786-Bromo-4H-imidazo[4,5-b]pyridineHCID 866810166-(Chloromethyl)-2-(methylthio)benzo[d]oxazole

Product 1

HCID 866810486-((6-bromo-3H-imidazo[4,5-b]pyridin-3-yl)methyl)-2-(methylthio)benzo[d]oxazoleYield 43.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 6-bromo-3H-imidazo[4,5-b]pyridine (200 mg, 1.01 mmol) in DMF (16 mL) was added NaH (60% dispersion in mineral oil, 581 mg, 1.44 mmol) portionwise at 0° C. After the mixture was stirred for 30 min, 6-(chloromethyl)-2-(methylthio)benzo[d]oxazole (203 mg, 0.96 mmol) was added. The reaction mixture was allowed to warm to rt and stir for 2 h. The reaction mixture was poured into water (40 mL) and extracted with ethyl acetate (60 mL×4). The combined organic layers were washed with water and brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by preparative TLC eluting with 15:1 DCM/MeOH to give 6-((6-bromo-3H-imidazo[4,5-b]pyridin-3-yl)methyl)-2-(methylthio)benzo[d]oxazole (156 mg, 43.2%) as a light yellow solid. 1H NMR (300 MHz, DMSO-d6) δ 8.47 (s, 1H), 8.22 (s, 1H), 8.04 (s, 1H), 7.56 (d, J=8.4 Hz, 1H), 7.40 (s, 1H), 7.26 (d, J=6.6 Hz, 1H), 5.53 (s, 2H), 2.74 (s, 3H). LCMS (ESI) m/z 374 (M+H)+.

Workup

  1. stirringstir for 2 h
  2. extractionextracted with ethyl acetate (60 mL×4)
  3. washThe combined organic layers were washed with water and brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by preparative TLC
  8. washeluting with 15:1 DCM/MeOH

Sources & evidence

ORD record
ord-d6f8da73f1994f2daafbf19fdc28605c
Source dataset
uspto-grants-2015_02
Patent number
US08952058B2

Reaction notes

Loading…