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

HRID 1786852Notes

Reaction equation

HRID 1786852 reaction equation
Cl[C:2]1[C:3]2[N:10]([CH2:11][C:12]3[CH:17]=[CH:16][C:15]([CH2:18][OH:19])=[CH:14][CH:13]=3)[CH:9]=[CH:8][C:4]=2[N:5]=[CH:6][N:7]=1.[Cl:20][C:21]1[CH:22]=[C:23]([CH:25]=[CH:26][C:27]=1[O:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[C:32]([F:36])[CH:31]=1)[NH2:24]>CN1CCCC1=O.C(OCC)(=O)C>[Cl:20][C:21]1[CH:22]=[C:23]([NH:24][C:2]2[C:3]3[N:10]([CH2:11][C:12]4[CH:17]=[CH:16][C:15]([CH2:18][OH:19])=[CH:14][CH:13]=4)[CH:9]=[CH:8][C:4]=3[N:5]=[CH:6][N:7]=2)[CH:25]=[CH:26][C:27]=1[O:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[C:32]([F:36])[CH:31]=1

Participants

5

Reactant 2

HCID 70592633-Chloro-4-(3-fluorobenzyloxy)anilineHCID 86084732{4-[(4-chloro-5H-pyrrolo[3,2-d]pyrimidin-5-yl)methyl]phenyl}methanol

Product 1

HCID 57597376(4-{[4-({3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidin-5-yl]methyl}phenyl)methanolYield 93%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
140 °C

Procedure

{4-[(4-Chloro-5H-pyrrolo[3,2-d]pyrimidin-5-yl)methyl]phenyl}methanol (354 mg) and 3-chloro-4-[(3-fluorobenzyl)oxy]aniline (488 mg) were dissolved in 1-methyl-2-pyrrolidone (2.58 mL), and the mixture was stirred with heating at 140° C. for 2 hrs. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate (80 mL) and partitioned with saturated aqueous sodium hydrogen carbonate (30 mL). The organic layer washed with saturated brine (30 mL), dried over magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified by silica gel column chromatography (eluent, hexane:ethyl acetate=80:20→0:100) to give the title compound (588 mg) as a powder.

Workup

  1. temperatureAfter cooling to room temperature
  2. custompartitioned with saturated aqueous sodium hydrogen carbonate (30 mL)
  3. washThe organic layer washed with saturated brine (30 mL)
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was separated
  7. custompurified by silica gel column chromatography (eluent, hexane:ethyl acetate=80:20→0:100)

Sources & evidence

ORD record
ord-4f9d637c337140aeb493704722b3ec7d
Source dataset
uspto-grants-2009_03
Patent number
US07507740B2

Reaction notes

Loading…