Cesium carbonate → Benzoic acid, 3-[(4-chloro-5H-pyrrolo[3,2-d]pyrimidin-5-yl)methyl]-, methyl ester

HRID 1925991Notes

Reaction equation

HRID 1925991 reaction equation
[Cl:1][C:2]1[C:3]2[NH:10][CH:9]=[CH:8][C:4]=2[N:5]=[CH:6][N:7]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:18][C:19]1[CH:20]=[C:21]([CH:26]=[CH:27][CH:28]=1)[C:22]([O:24][CH3:25])=[O:23]>CN(C)C=O.O>[Cl:1][C:2]1[C:3]2[N:10]([CH2:18][C:19]3[CH:20]=[C:21]([CH:26]=[CH:27][CH:28]=3)[C:22]([O:24][CH3:25])=[O:23])[CH:9]=[CH:8][C:4]=2[N:5]=[CH:6][N:7]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 517981Methyl 3-(bromomethyl)benzoateHCID 53706954-chloro-5H-pyrrolo[3,2-d]pyrimidine

Product 1

HCID 86615755Benzoic acid, 3-[(4-chloro-5H-pyrrolo[3,2-d]pyrimidin-5-yl)methyl]-, methyl esterYield 54.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a suspension of 4-chloro-5H-pyrrolo[3,2-d]pyrimidine (300 mg) in N,N-dimethylformamide (2.0 mL) was added cesium carbonate (955 mg) under ice-cooling, and the mixture was stirred while warming to room temperature for 15 min. To the reaction mixture was added methyl 3-(bromomethyl)benzoate (671 mg), and the mixture was stirred at room temperature for 4 hrs. The reaction mixture was diluted with water (40 mL), and extracted with a mixed solvent (40 mL×3) of ethyl acetate/tetrahydrofuran (1/1). The organic layer was washed with saturated brine (120 mL×3) and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the obtained residue was subjected to silica gel column chromatography (silica gel, eluent:hexane/ethyl acetate=80/20→10/90). The object fraction was concentrated under reduced pressure. Chloroform/diisopropyl ether (4/1) was added to the residue, and the resultant precipitate was collected by filtration, washed and dried under reduced pressure to give the title compound (319 mg) as a pale-brown powder.

Workup

  1. temperaturecooling
  2. stirringthe mixture was stirred at room temperature for 4 hrs
  3. extractionextracted with a mixed solvent (40 mL×3) of ethyl acetate/tetrahydrofuran (1/1)
  4. washThe organic layer was washed with saturated brine (120 mL×3)
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customThe solvent was evaporated under reduced pressure
  7. concentrationThe object fraction was concentrated under reduced pressure
  8. additionChloroform/diisopropyl ether (4/1) was added to the residue
  9. filtrationthe resultant precipitate was collected by filtration
  10. washwashed
  11. customdried under reduced pressure

Sources & evidence

ORD record
ord-8f5c9dc3409b4950a889e9a8d73bc984
Source dataset
uspto-grants-2012_05
Patent number
US08178543B2

Reaction notes

Loading…