(+/-)-N-{2-[1-(3-benzyl-7-chloro-4-oxo-3,4-dihydro-quinazolin-2-yl)-2-methyl-propylamino]-1,1-dimethyl-ethyl}-3-fluoro-4-methyl-benzamide → (+/-)-3-benzyl-7-chloro-2-{1-[2-(3-fluoro-4-methyl-phenyl)-4,4-dimethyl-4,5-dihydro-imidazol-1-yl]-2-methyl-propyl}-3H-quinazolin-4-one

HRID 490258Notes

Reaction equation

HRID 490258 reaction equation
[CH2:1]([N:8]1[C:17](=[O:18])[C:16]2[C:11](=[CH:12][C:13]([Cl:19])=[CH:14][CH:15]=2)[N:10]=[C:9]1[CH:20]([NH:24][CH2:25][C:26]([NH:29][C:30](=O)[C:31]1[CH:36]=[CH:35][C:34]([CH3:37])=[C:33]([F:38])[CH:32]=1)([CH3:28])[CH3:27])[CH:21]([CH3:23])[CH3:22])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>P(Cl)(Cl)(Cl)=O>[CH2:1]([N:8]1[C:17](=[O:18])[C:16]2[C:11](=[CH:12][C:13]([Cl:19])=[CH:14][CH:15]=2)[N:10]=[C:9]1[CH:20]([N:24]1[CH2:25][C:26]([CH3:28])([CH3:27])[N:29]=[C:30]1[C:31]1[CH:36]=[CH:35][C:34]([CH3:37])=[C:33]([F:38])[CH:32]=1)[CH:21]([CH3:23])[CH3:22])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

3

Reactant 1

HCID 21097059(+/-)-N-{2-[1-(3-benzyl-7-chloro-4-oxo-3,4-dihydro-quinazolin-2-yl)-2-methyl-propylamino]-1,1-dimethyl-ethyl}-3-fluoro-4-methyl-benzamide

Product 1

HCID 21097016(+/-)-3-benzyl-7-chloro-2-{1-[2-(3-fluoro-4-methyl-phenyl)-4,4-dimethyl-4,5-dihydro-imidazol-1-yl]-2-methyl-propyl}-3H-quinazolin-4-oneYield 55%

Reagents, catalysts & solvents 1

HCID 24813Phosphorus oxychlorideSolvent

Procedure

A solution of (±)-N-{2-[1-(3-benzyl-7-chloro-4-oxo-3,4-dihydro-quinazolin-2-yl)-2-methyl-propylamino]-1,1-dimethyl-ethyl}-3-fluoro-4-methyl-benzamide (120 mg, 0.219 mmol) in phosphorus oxychloride (2 mL) was heated at reflux. After 8 hours, the reaction mixture was allowed to cool to ambient temperature and concentrated under reduced pressure. The residue was dissolved in dichloromethane (10 mL) and washed with two 10 mL portions of saturated aqueous sodium bicarbonte. The combined aqueous layers were extracted with dichloromethane and the extracts were dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography (3% methanol/dichloromethane) to give (±)-3-benzyl-7-chloro-2-{1-[2-(3-fluoro-4-methyl-phenyl)-4,4-dimethyl-4,5-dihydro-imidazol-1-yl]-2-methyl-propyl}-3H-quinazolin-4-one (64 mg, 55%) as a white solid: LCMS 531 (M++H)

Workup

  1. temperatureat reflux
  2. concentrationconcentrated under reduced pressure
  3. dissolutionThe residue was dissolved in dichloromethane (10 mL)
  4. washwashed with two 10 mL portions of saturated aqueous sodium bicarbonte
  5. extractionThe combined aqueous layers were extracted with dichloromethane
  6. dry with materialthe extracts were dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel chromatography (3% methanol/dichloromethane)

Sources & evidence

ORD record
ord-17880b96b9df47d6b56c8ec553a13806
Source dataset
uspto-grants-2009_05
Patent number
US07528137B2

Reaction notes

Loading…