Triethylamine → N-(2-[4-({3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidin-5-yl]ethyl)-N'-methoxyurea

HRID 1926168Notes

Reaction equation

HRID 1926168 reaction equation
Cl.[CH3:2][O:3][NH2:4].C(N(CC)CC)C.Cl.Cl.[NH2:14][CH2:15][CH2:16][N:17]1[C:25]2[C:24]([NH:26][C:27]3[CH:32]=[CH:31][C:30]([O:33][C:34]4[CH:39]=[CH:38][CH:37]=[C:36]([C:40]([F:43])([F:42])[F:41])[CH:35]=4)=[C:29]([Cl:44])[CH:28]=3)=[N:23][CH:22]=[N:21][C:20]=2[CH:19]=[CH:18]1.[C:45](=O)([O-])[OH:46].[Na+]>CN(C)C=O.[Cl-].[Na+].O>[Cl:44][C:29]1[CH:28]=[C:27]([NH:26][C:24]2[C:25]3[N:17]([CH2:16][CH2:15][NH:14][C:45]([NH:4][O:3][CH3:2])=[O:46])[CH:18]=[CH:19][C:20]=3[N:21]=[CH:22][N:23]=2)[CH:32]=[CH:31][C:30]=1[O:33][C:34]1[CH:39]=[CH:38][CH:37]=[C:36]([C:40]([F:43])([F:42])[F:41])[CH:35]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 521874O-Methylhydroxylamine hydrochlorideHCID 568513565-(2-aminoethyl)-N-{3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidin-4-amine dihydrochloride

Product 1

HCID 57597176N-(2-[4-({3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidin-5-yl]ethyl)-N'-methoxyurea

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution of N,N′-carbonyldiimidazole (187 mg) in N,N-dimethylformamide (2 mL) were added O-methylhydroxylamine hydrochloride (96 mg) and triethylamine (0.27 mL) under ice-cooling, and the mixture was stirred at room temperature for 30 min. A solution of 5-(2-aminoethyl)-N-{3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidin-4-amine dihydrochloride (200 mg) in N,N-dimethylformamide (5 mL) was added. The reaction mixture was stirred at room temperature for 22 hrs, aqueous sodium hydrogen carbonate and brine were added under ice-cooling, and the mixture was extracted twice with ethyl acetate. The organic layers were collected, dried over anhydrous magnesium sulfate and concentrated. The residue was purified by silica gel column chromatography (eluent, ethyl acetate:methanol=100:0→80:20) and further recrystallized from ethyl acetate/diisopropyl ether to give the title compound (116 mg) as crystals.

Workup

  1. temperaturecooling
  2. stirringThe reaction mixture was stirred at room temperature for 22 hrs
  3. temperaturecooling
  4. extractionthe mixture was extracted twice with ethyl acetate
  5. customThe organic layers were collected
  6. dry with materialdried over anhydrous magnesium sulfate
  7. concentrationconcentrated
  8. customThe residue was purified by silica gel column chromatography (eluent, ethyl acetate:methanol=100:0→80:20)
  9. customfurther recrystallized from ethyl acetate/diisopropyl ether

Sources & evidence

ORD record
ord-6a330f9cba5e423f9a653a3d0a1dcaaf
Source dataset
uspto-grants-2012_05
Patent number
US08178543B2

Reaction notes

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