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

HRID 1805874Notes

Reaction equation

HRID 1805874 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].[Cl:14][C:15]1[N:16]=[C:17](Cl)[C:18]2[N:23]([CH3:24])[CH:22]=[CH:21][C:19]=2[N:20]=1>CN1C(=O)CCC1.O>[Cl:14][C:15]1[N:16]=[C:17]([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:18]2[N:23]([CH3:24])[CH:22]=[CH:21][C:19]=2[N:20]=1

Participants

6

Reactant 3

HCID 201763,5-Dimethyl-4-hydroxybenzonitrileHCID 24758Sodium hydrideHCID 147277632,4-dichloro-5-methyl-5H-pyrrolo(3,2-d)pyrimidine

Product 1

HCID 576936264-(2-Chloro-5-methyl-5H-pyrrolo[3,2-d]pyrimidin-4-yloxy)-3,5-dimethylbenzonitrileYield 89.5%

Reagents, catalysts & solvents 2

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

Procedure

To a stirred solution of NaH (42.1 mg, 1.05 mmol) in dry NMP (2.5 mL) was added 4-hydroxy-3,5-dimethylbenzonitrile (154.7 mg, 1.05 mmol) and stirred at room temperature for 30 min under argon. The reaction mixture was added to a solution of 2,4-dichloro-5-methyl-5H-pyrrolo[3,2-d]pyrimidine (211.3 mg, 1.05 mmol) in dry NMP (2.7 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, brine, dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by column chromatography, eluting with hexanes/ethyl acetate (3:1-1:1), to give the product as a light yellow solid (294 mg, 85%).

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, 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 (3:1-1:1)

Sources & evidence

ORD record
ord-130f2b5d2ea249dd8e099a319e53841a
Source dataset
uspto-grants-2013_01
Patent number
US08354532B2

Reaction notes

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