3,5-Dimethyl-4-hydroxybenzonitrile → 4-(2-Amino-5-benzyl-5H-pyrrolo[3,2-d]pyrimidin-4-yloxy)-3,5-dimethylbenzonitrile

HRID 1516842Notes

Reaction equation

HRID 1516842 reaction equation
[H-].[Na+].[OH:3][C:4]1[C:11]([CH3:12])=[CH:10][C:7]([C:8]#[N:9])=[CH:6][C:5]=1[CH3:13].[CH2:14]([N:21]1[C:29]2[C:28](Cl)=[N:27][C:26]([NH2:31])=[N:25][C:24]=2[CH:23]=[CH:22]1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>CN1C(=O)CCC1.O>[NH2:31][C:26]1[N:27]=[C:28]([O:3][C:4]2[C:5]([CH3:13])=[CH:6][C:7]([C:8]#[N:9])=[CH:10][C:11]=2[CH3:12])[C:29]2[N:21]([CH2:14][C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=3)[CH:22]=[CH:23][C:24]=2[N:25]=1

Participants

6

Reactant 3

HCID 201763,5-Dimethyl-4-hydroxybenzonitrileHCID 24758Sodium hydrideHCID 576936175-benzyl-4-chloro-5H-pyrrolo[3,2-d]pyrimidin-2-amine

Product 1

HCID 576936694-(2-Amino-5-benzyl-5H-pyrrolo[3,2-d]pyrimidin-4-yloxy)-3,5-dimethylbenzonitrileYield 60%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent2×

Procedure

To a stirred suspension of NaH (155 mg, 6.47 mmol) in dry NMP (4 mL) was added 4-hydroxy-3,5-dimethylbenzonitrile (570 mg, 3.88 mmol), and the mixture was stirred at room temperature for 30 min under argon. The reaction mixture was added to a solution of 5-benzyl-4-chloro-5H-pyrrolo[3,2-d]pyrimidin-2-amine (400 mg, 1.55 mmol) in dry NMP (4 mL) and heated at 160° C. for 16 h. After completion of the reaction, the resulting mixture was diluted with water and washed with EtOAc. The combined organic layers were washed with water, 2% NaOH, brine, dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by column chromatography, eluting with hexanes/ethyl acetate (2:1-1:4) to give the product as a light yellow solid (342 mg, 60%).

Workup

  1. temperatureheated at 160° C. for 16 h
  2. customAfter completion of the reaction
  3. washwashed with EtOAc
  4. washThe combined organic layers were washed with water, 2% NaOH, brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by column chromatography
  9. washeluting with hexanes/ethyl acetate (2:1-1:4)

Sources & evidence

ORD record
ord-7b282f1b78fd4c08bc34b7e9cca7090e
Source dataset
uspto-grants-2012_07
Patent number
US08227601B2

Reaction notes

Loading…