Water → 2-(2,6-dimethyl-pyridin-4-yl)-7-fluoro-5-(2-pyrrolidin-1-yl-ethoxy)-3H-quinazolin-4-one

HRID 591810Notes

Reaction equation

HRID 591810 reaction equation
[N:1]1([CH2:6][CH2:7][OH:8])[CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].[Na+].[CH3:11][C:12]1[CH:17]=[C:16]([C:18]2[NH:27][C:26](=[O:28])[C:25]3[C:20](=[CH:21][C:22]([F:30])=[CH:23][C:24]=3F)[N:19]=2)[CH:15]=[C:14]([CH3:31])[N:13]=1.O>CN(C=O)C.C(O)(=O)C>[CH3:11][C:12]1[CH:17]=[C:16]([C:18]2[NH:27][C:26](=[O:28])[C:25]3[C:20](=[CH:21][C:22]([F:30])=[CH:23][C:24]=3[O:8][CH2:7][CH2:6][N:1]3[CH2:5][CH2:4][CH2:3][CH2:2]3)[N:19]=2)[CH:15]=[C:14]([CH3:31])[N:13]=1

Participants

7

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 762881-PyrrolidineethanolHCID 1363480062-(2,6-dimethylpyridin-4-yl)-5,7-difluoro-3H-quinazolin-4-one

Product 1

HCID 1363480592-(2,6-dimethyl-pyridin-4-yl)-7-fluoro-5-(2-pyrrolidin-1-yl-ethoxy)-3H-quinazolin-4-one

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-pyrrolidin-1-yl-ethanol (5.09 g, 44.2 mmol) in DMF (10 mL) was added sodium hydride (60% suspension in mineral oil, 0.88 g, 22.1 mmol) in small portions and the reaction mixture was stirred at room temperature for 30 minutes. To this mixture was added 2-(2,6-dimethyl-pyridin-4-yl)-5,7-difluoro-3H-quinazolin-4-one 0.63 g, 2.21 mmol) and the reaction mixture was stirred at room temperature for 16 hours. Water (20 mL) was added, and the mixture was neutralized, to pH approximately 6 with acetic acid. Solvent was evaporated, and the residue was dissolved in ethyl acetate, washed with water, and dried over anhydrous sodium sulfate, and concentrated in vacuo. The crude compound was purified by the Simpliflash system (0-4% methanol in CH2Cl2 as eluent) to give 2-(2,6-dimethyl-pyridin-4-yl)-7-fluoro-5-(2-pyrrolidin-1-yl-ethoxy)-3H-quinazolin-4-one as a yellow solid. Yield: 0.61 g (72%).

Workup

  1. stirringwas stirred at room temperature for 16 hours
  2. customSolvent was evaporated
  3. dissolutionthe residue was dissolved in ethyl acetate
  4. washwashed with water
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe crude compound was purified by the Simpliflash system (0-4% methanol in CH2Cl2 as eluent)

Sources & evidence

ORD record
ord-9709fc6c6a7e4092add8140f8e71598d
Source dataset
uspto-grants-2016_01
Patent number
US09238640B2

Reaction notes

Loading…