Triethylamine → (+/-)-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

HRID 490257Notes

Reaction equation

HRID 490257 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:39]=[C:40]([CH:44]=[CH:45][C:46]=1[CH3:47])[C:41](Cl)=[O:42]>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]([NH:4][CH2:3][C:2]([NH:1][C:41](=[O:42])[C:40]1[CH:44]=[CH:45][C:46]([CH3:47])=[C:38]([F:37])[CH:39]=1)([CH3:29])[CH3:28])[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 27348753-Fluoro-4-methylbenzoyl chlorideHCID 21097057(+/-)-2-[1-(2-amino-2-methyl-propylamino)-2-methyl-propyl]-3-benzyl-7-chloro-3H-quinazolin-4-one

Product 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-benzamideYield 68.3%

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 (133 mg, 0.32 mmol) in dichloromethane (3 mL) was added triethylamine (90 μL, 0.64 mmol), followed by 3-fluoro-4-methylbenzoyl chloride (51 μL, 0.35 mmol). The resultant solution was stirred at ambient temperature for 3 hours, quenched with saturated aqueous sodium bicarbonate (5 mL) and diluted with dichloromethane (5 mL). The aqueous layer was extracted with dichloromethane (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 (10-20% ethyl acetate/hexanes) to give (±)-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, 68%) as a white solid.

Workup

  1. customquenched with saturated aqueous sodium bicarbonate (5 mL)
  2. additiondiluted with dichloromethane (5 mL)
  3. extractionThe aqueous layer was extracted with dichloromethane (5 mL)
  4. dry with materialthe combined extracts were dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel chromatography (10-20% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-da2d63f286d34b8296954e783373a36d
Source dataset
uspto-grants-2009_05
Patent number
US07528137B2

Reaction notes

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