Cesium carbonate → 3-{4-[2-(2-Cyclopropylmethoxy-pyridin-3-yl)-5,6-difluoro-benzoimidazol-1-ylmethyl]-phenyl}-propionic acid methyl ester

HRID 1875740Notes

Reaction equation

HRID 1875740 reaction equation
[CH3:1][O:2][C:3](=[O:31])[CH2:4][CH2:5][C:6]1[CH:11]=[CH:10][C:9]([CH2:12][N:13]2[C:17]3[CH:18]=[C:19]([F:23])[C:20]([F:22])=[CH:21][C:16]=3[N:15]=[C:14]2[C:24]2[C:25]([OH:30])=[N:26][CH:27]=[CH:28][CH:29]=2)=[CH:8][CH:7]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:39][CH:40]1[CH2:42][CH2:41]1>CC(C)=O>[CH3:1][O:2][C:3](=[O:31])[CH2:4][CH2:5][C:6]1[CH:7]=[CH:8][C:9]([CH2:12][N:13]2[C:17]3[CH:18]=[C:19]([F:23])[C:20]([F:22])=[CH:21][C:16]=3[N:15]=[C:14]2[C:24]2[C:25]([O:30][CH2:39][CH:40]3[CH2:42][CH2:41]3)=[N:26][CH:27]=[CH:28][CH:29]=2)=[CH:10][CH:11]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 81503BromomethylcyclopropaneHCID 1784998703-{4-[5,6-Difluoro-2-(2-hydroxy-pyridin-3-yl)-benzoimidazol-1-ylmethyl]-phenyl}-propionic acid methyl ester

Product 1

HCID 670498103-{4-[2-(2-Cyclopropylmethoxy-pyridin-3-yl)-5,6-difluoro-benzoimidazol-1-ylmethyl]-phenyl}-propionic acid methyl esterYield 67%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

To a stirred solution of 3-{4-[5,6-difluoro-2-(2-hydroxy-pyridin-3-yl)-benzoimidazol-1-ylmethyl]-phenyl}-propionic acid methyl ester (72 mg, 0.17 mmol) in acetone (10 ml) was added cesium carbonate (85 mg, 0.26 mmol) followed by bromomethyl-cyclopropane (26 mg, 0.19 mmol; CAS Reg. No. 7051-34-5) and the reaction was refluxed for 2 h. The reaction mixture was filtered and the filtrate removed under reduced pressure. The residue was purified by column chromatography using silica gel (50-60% ethyl acetate/n-hexane) to afford the desired product as a brown solid (67%). MS (Turbo Spray): m/z=478.5 (M+H).

Workup

  1. temperature7051-34-5) and the reaction was refluxed for 2 h
  2. filtrationThe reaction mixture was filtered
  3. customthe filtrate removed under reduced pressure
  4. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-e8ced4dc4ebc4f7c9ca4f8a1de028cbe
Source dataset
uspto-grants-2012_11
Patent number
US08309581B2

Reaction notes

Loading…