2-(Methylamino)ethanol → 2-[{3-[4-({3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidin-5-yl]propyl}(methyl)amino]ethanol dihydrochloride

HRID 1926107Notes

Reaction equation

HRID 1926107 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:17][C:18]2[C:19]3[N:26]([CH2:27][CH2:28][CH2:29]Cl)[CH:25]=[CH:24][C:20]=3[N:21]=[CH:22][N:23]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=1.[CH3:31][NH:32][CH2:33][CH2:34][OH:35]>CN(C)C=O>[ClH:1].[ClH:1].[Cl:1][C:2]1[CH:3]=[C:4]([NH:17][C:18]2[C:19]3[N:26]([CH2:27][CH2:28][CH2:29][N:32]([CH3:31])[CH2:33][CH2:34][OH:35])[CH:25]=[CH:24][C:20]=3[N:21]=[CH:22][N:23]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=1

Participants

4

Reactant 2

HCID 80162-(Methylamino)ethanolHCID 67520636N-{3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}-5-(3-chloropropyl)-5H-pyrrolo[3,2-d]pyrimidin-4-amine

Product 1

HCID 675212082-[{3-[4-({3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidin-5-yl]propyl}(methyl)amino]ethanol dihydrochlorideYield 197.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of N-{3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}-5-(3-chloropropyl)-5H-pyrrolo[3,2-d]pyrimidin-4-amine (634 mg), 2-methylaminoethanol (534 mg) and N,N-dimethylformamide (5 mL) was stirred at room temperature for 64 hrs. After concentration under reduced pressure, saturated aqueous sodium hydrogen carbonate (10 mL) was added to the residue, and the mixture was extracted with ethyl acetate (55 mL×2). The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by basic silica gel column chromatography (eluent, hexane:ethyl acetate=80:20→0:100). 4N Hydrogen chloride-ethyl acetate solution (10 mL) was added to the obtained amorphous solid and, after concentration under reduced pressure, the residue was recrystallized from ethanol-ethyl acetate to give the title compound (523 mg).

Workup

  1. concentrationAfter concentration under reduced pressure, saturated aqueous sodium hydrogen carbonate (10 mL)
  2. additionwas added to the residue
  3. extractionthe mixture was extracted with ethyl acetate (55 mL×2)
  4. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by basic silica gel column chromatography (eluent, hexane:ethyl acetate=80:20→0:100)
  7. addition4N Hydrogen chloride-ethyl acetate solution (10 mL) was added to the obtained amorphous solid
  8. concentrationafter concentration under reduced pressure
  9. customthe residue was recrystallized from ethanol-ethyl acetate

Sources & evidence

ORD record
ord-008aff4f21704a00a3bc1e1a9147172c
Source dataset
uspto-grants-2012_05
Patent number
US08178543B2

Reaction notes

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