3,5-Dimethyl-4-hydroxybenzonitrile → 4-(2-Chlorothieno[2,3-d]pyrimidin-4-yloxy)-3,5-dimethylbenzonitrile

HRID 736317Notes

Reaction equation

HRID 736317 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[CH:23]=[CH:22][S:21][C:19]=2[N:20]=1>C1COCC1.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[CH:23]=[CH:22][S:21][C:19]=2[N:20]=1

Participants

6

Reactant 3

HCID 201763,5-Dimethyl-4-hydroxybenzonitrileHCID 24758Sodium hydrideHCID 122173242,4-Dichlorothieno[2,3-d]pyrimidine

Product 1

HCID 578488784-(2-Chlorothieno[2,3-d]pyrimidin-4-yloxy)-3,5-dimethylbenzonitrileYield 28.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A stirred suspension of NaH (85 mg, 2.12 mmol) in dry THF (12 mL) was added 4-hydroxy-3,5-dimethyl benzonitrile (311 mg, 2.12 mmol) and stirred at room temperature for 30 min under Argon. The reaction mixture was added to a solution of 2,4-dichlorothieno[2,3-d]pyrimidine (434 mg, 2.12 mmol) in dry THF (10 mL) and heated at 50° C. for 2 h, 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 (5:1) to give the product as a white solid (188 mg, 28%):

Workup

  1. temperatureheated at 50° C. for 2 h
  2. washwashed with EtOAc
  3. washThe combined organic layers were washed with water, brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by column chromatography
  8. washeluting with hexanes/ethyl acetate (5:1)

Sources & evidence

ORD record
ord-2e5df11d727d41038035243a2da3f400
Source dataset
uspto-grants-2009_09
Patent number
US07595324B2

Reaction notes

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