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

HRID 490259Notes

Reaction equation

HRID 490259 reaction equation
[NH2:1][C:2]([CH3:29])([CH3:28])[CH2:3][NH:4][CH:5]([C:9]1[N:18]([CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:17](=[O:26])[C:16]2[C:11](=[CH:12][C:13]([Cl:27])=[CH:14][CH:15]=2)[N:10]=1)[CH:6]([CH3:8])[CH3:7].C(N(CC)CC)C.[F:37][C:38]1[CH:46]=[CH:45][C:41]([C:42](Cl)=O)=[CH:40][C:39]=1[CH3:47]>ClCCl>[CH2:19]([N:18]1[C:17](=[O:26])[C:16]2[C:11](=[CH:12][C:13]([Cl:27])=[CH:14][CH:15]=2)[N:10]=[C:9]1[CH:5]([N:4]1[CH2:3][C:2]([CH3:29])([CH3:28])[N:1]=[C:42]1[C:41]1[CH:45]=[CH:46][C:38]([F:37])=[C:39]([CH3:47])[CH:40]=1)[CH:6]([CH3:8])[CH3:7])[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 27745894-Fluoro-3-methylbenzoyl chlorideHCID 21097057(+/-)-2-[1-(2-amino-2-methyl-propylamino)-2-methyl-propyl]-3-benzyl-7-chloro-3H-quinazolin-4-one

Product 1

HCID 21097023(+/-)-3-benzyl-7-chloro-2-{1-[2-(4-fluoro-3-methyl-phenyl)-4,4-dimethyl-4,5 dihydro-imidazol-1-yl]-2-methyl-propyl}-3H-quinazolin-4-oneYield 43%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (±)-2-[1-(2-amino-2-methyl-propylamino)-2-methyl-propyl]-3-benzyl-7-chloro-3H-quinazolin-4-one (250 mg, 0.61 mmol) in dichloromethane (10 mL) was added triethylamine (295 μL, 2.12 mmol), followed by 4-fluoro-3-methylbenzoyl chloride (105 mg, 0.61 mmol). The resultant solution was stirred at ambient temperature for 2 hours, then evaporated under reduced pressure to a crude white solid. The resultant solid was treated with glacial acetic acid (10 mL) then the resultant suspention was heated at reflux for 48 hours. The reaction was cooled to ambient temperature then evaporated under reduced pressure to a crude oil. The oil was quenched with saturated aqueous sodium bicarbonate (10 mL) and brine (5 mL). The aqueous layer was extracted with dichloromethane (2×5 mL) and the combined extracts were dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography (5-10% ethyl acetate/hexanes) to furnish (±)-3-benzyl-7-chloro-2-{1-[2-(4-fluoro-3-methyl-phenyl)-4,4-dimethyl-4,5-dihydro-imidazol-1-yl]-2-methyl-propyl}-3H-quinazolin-4-one (138 mg, 43%) as a white solid: LCMS 531 (M++H)

Workup

  1. customevaporated under reduced pressure to a crude white solid
  2. additionThe resultant solid was treated with glacial acetic acid (10 mL)
  3. temperaturethe resultant suspention was heated
  4. temperatureat reflux for 48 hours
  5. customthen evaporated under reduced pressure to a crude oil
  6. customThe oil was quenched with saturated aqueous sodium bicarbonate (10 mL) and brine (5 mL)
  7. extractionThe aqueous layer was extracted with dichloromethane (2×5 mL)
  8. dry with materialthe combined extracts were dried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified by silica gel chromatography (5-10% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-984e29dcc21d44c49d598e2208079cba
Source dataset
uspto-grants-2009_05
Patent number
US07528137B2

Reaction notes

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