Phenol → 2-{2-[4-({3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}amino)-6-methyl-5H-pyrrolo[3,2-d]pyrimidin-5-yl]ethoxy}ethyl benzoate

HRID 1926117Notes

Reaction equation

HRID 1926117 reaction equation
[C:1]([O:9][CH2:10][CH2:11][O:12][CH2:13][CH2:14][N:15]1[C:23]2[C:22](OC3C=CC=CC=3)=[N:21][CH:20]=[N:19][C:18]=2[CH:17]=[C:16]1[CH3:31])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:32][C:33]1[CH:34]=[C:35]([CH:37]=[CH:38][C:39]=1[O:40][CH2:41][C:42]1[CH:47]=[CH:46][CH:45]=[C:44]([F:48])[CH:43]=1)[NH2:36].Cl.N1C=CC=CC=1.C1(O)C=CC=CC=1>ClCCl>[C:1]([O:9][CH2:10][CH2:11][O:12][CH2:13][CH2:14][N:15]1[C:23]2[C:22]([NH:36][C:35]3[CH:37]=[CH:38][C:39]([O:40][CH2:41][C:42]4[CH:47]=[CH:46][CH:45]=[C:44]([F:48])[CH:43]=4)=[C:33]([Cl:32])[CH:34]=3)=[N:21][CH:20]=[N:19][C:18]=2[CH:17]=[C:16]1[CH3:31])(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 996Phenol2×HCID 70592633-Chloro-4-(3-fluorobenzyloxy)anilineHCID 10176127Pyridinium chloride2×HCID 568510562-[2-(6-methyl-4-phenoxy-5H-pyrrolo[3,2-d]pyrimidin-5-yl)ethoxy]ethyl benzoate

Product 1

HCID 675213062-{2-[4-({3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}amino)-6-methyl-5H-pyrrolo[3,2-d]pyrimidin-5-yl]ethoxy}ethyl benzoateYield 26.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 2-[2-(6-methyl-4-phenoxy-5H-pyrrolo[3,2-d]pyrimidin-5-yl)ethoxy]ethyl benzoate (92.3 mg), 3-chloro-4-[(3-fluorobenzyl)oxy]aniline (86.3 mg), pyridine hydrochloride (81.6 mg) and phenol (156.1 mg) was stirred at 120° C. for 3 hrs, and at 140° C. for 5.5 hrs. Further, pyridine hydrochloride (77.6 mg) and phenol (188.7 mg) were added, and the mixture was stirred at 140° C. for 22.5 hrs. The reaction mixture was diluted with dichloromethane, washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified by basic silica gel column chromatography (eluent, hexane:ethyl acetate=50:50→0:100) to give the title compound (33.3 mg) as a purple oil.

Workup

  1. waitat 140° C. for 5.5 hrs
  2. stirringthe mixture was stirred at 140° C. for 22.5 hrs
  3. washwashed with saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was separated
  7. custompurified by basic silica gel column chromatography (eluent, hexane:ethyl acetate=50:50→0:100)

Sources & evidence

ORD record
ord-64bfcfd49c0348e392b9ca9c2e75b2fc
Source dataset
uspto-grants-2012_05
Patent number
US08178543B2

Reaction notes

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