3-Chloro-4-(3-fluorobenzyloxy)aniline → 2-{2-[4-({3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidin-5-yl]ethoxy}ethyl benzoate

HRID 1786967Notes

Reaction equation

HRID 1786967 reaction equation
[C:1]([O:9][CH2:10][CH2:11][O:12][CH2:13][CH2:14][N:15]1[C:23]2[C:22](Cl)=[N:21][CH:20]=[N:19][C:18]=2[CH:17]=[CH:16]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:25][C:26]1[CH:27]=[C:28]([CH:30]=[CH:31][C:32]=1[O:33][CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[C:37]([F:41])[CH:36]=1)[NH2:29]>CN1CCCC1=O.C(=O)([O-])O.[Na+]>[C:1]([O:9][CH2:10][CH2:11][O:12][CH2:13][CH2:14][N:15]1[C:23]2[C:22]([NH:29][C:28]3[CH:30]=[CH:31][C:32]([O:33][CH2:34][C:35]4[CH:40]=[CH:39][CH:38]=[C:37]([F:41])[CH:36]=4)=[C:26]([Cl:25])[CH:27]=3)=[N:21][CH:20]=[N:19][C:18]=2[CH:17]=[CH:16]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 70592633-Chloro-4-(3-fluorobenzyloxy)anilineHCID 568508032-(2-(4-Chloro-5H-pyrrolo[3,2-d]pyrimidin-5-yl)ethoxy)ethyl benzoate

Product 1

HCID 675207292-{2-[4-({3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidin-5-yl]ethoxy}ethyl benzoateYield 87.7%

Reagents, catalysts & solvents 2

HCID 13387N-methyl-2-pyrrolidoneSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 2-[2-(4-chloro-5H-pyrrolo[3,2-d]pyrimidin-5-yl)ethoxy]ethyl benzoate (802 mg) in 1-methyl-2-pyrrolidone (8.0 mL) was added 3-chloro-4-[(3-fluorobenzyl)oxy]aniline (745 mg), and the mixture was stirred in an oil bath at a temperature of 100° C. for 2 hrs. The reaction mixture was allowed to cool to room temperature, diluted with 5% aqueous sodium hydrogen carbonate solution (25 mL), and extracted with a mixed solvent (50 mL×3) of ethyl acetate/tetrahydrofuran (3/1). The solvent was evaporated under reduced pressure, and the obtained residue was subjected to basic silica gel chromatography (eluent:hexane/ethyl acetate=95/5→0/100). The object fraction was concentrated under reduced pressure and dried to give the title compound (1141 mg) as a yellow amorphous solid.

Workup

  1. temperatureto cool to room temperature
  2. extractionextracted with a mixed solvent (50 mL×3) of ethyl acetate/tetrahydrofuran (3/1)
  3. customThe solvent was evaporated under reduced pressure
  4. concentrationThe object fraction was concentrated under reduced pressure
  5. customdried

Sources & evidence

ORD record
ord-aa93349175704aa0b74322613ac8dc75
Source dataset
uspto-grants-2009_03
Patent number
US07507740B2

Reaction notes

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