1,8-Diazabicyclo(5.4.0)undec-7-ene → 4-Quinazolineacetic acid, 8-fluoro-3,4-dihydro-2-[4-(3-methoxyphenyl)-1-piperazinyl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-, methyl ester

HRID 661328Notes

Reaction equation

HRID 661328 reaction equation
[CH3:1][O:2][C:3](=[O:29])[CH2:4][CH:5]1[C:14]2[C:9](=[C:10]([F:15])[CH:11]=[CH:12][CH:13]=2)[N:8]=[C:7](Cl)[N:6]1[C:17]1[CH:22]=[C:21]([C:23]([F:26])([F:25])[F:24])[CH:20]=[CH:19][C:18]=1[O:27][CH3:28].[CH3:30][O:31][C:32]1[CH:33]=[C:34]([N:38]2[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]2)[CH:35]=[CH:36][CH:37]=1.C1CCN2C(=NCCC2)CC1>O1CCOCC1.C(OCC)(=O)C.O>[CH3:1][O:2][C:3](=[O:29])[CH2:4][CH:5]1[C:14]2[C:9](=[C:10]([F:15])[CH:11]=[CH:12][CH:13]=2)[N:8]=[C:7]([N:41]2[CH2:40][CH2:39][N:38]([C:34]3[CH:35]=[CH:36][CH:37]=[C:32]([O:31][CH3:30])[CH:33]=3)[CH2:43][CH2:42]2)[N:6]1[C:17]1[CH:22]=[C:21]([C:23]([F:26])([F:25])[F:24])[CH:20]=[CH:19][C:18]=1[O:27][CH3:28]

Participants

7

Reactant 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 81430N-(3-methoxyphenyl)piperazineHCID 120020734-Quinazolineacetic acid, 2-chloro-8-fluoro-3,4-dihydro-3-[2-methoxy-5-(trifluoromethyl)phenyl]-, methyl ester

Product 1

HCID 119836914-Quinazolineacetic acid, 8-fluoro-3,4-dihydro-2-[4-(3-methoxyphenyl)-1-piperazinyl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-, methyl esterYield 87.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

Methyl{2-chloro-8-fluoro-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4-dihydroquinazolin-4-yl}acetate (52.5 g) is dissolved in 1,4-dioxane (100 ml), 3-methoxyphenylpiperazine (25.8 g) and DBU (20.4 g) are added at room temperature, the temperature increasing. The mixture is stirred under reflux for 22 h, then cooled to room temperature, diluted with ethyl acetate (500 ml) and water (200 ml) and the phases are separated. The organic phase is washed with 0.2N hydrochloric acid (three times 100 ml) and water (200 ml), dried over sodium sulphate and concentrated in a rotary evaporator. A total of 62.5 g of methyl{8-fluoro-2-[4-(3-methoxyphenyl)piperazin-1-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4-dihydroquinazolin-4-yl}acetate is obtained as a solidified foam, which is reacted as the crude product without further purification.

Workup

  1. temperaturethe temperature increasing
  2. temperatureunder reflux for 22 h
  3. customthe phases are separated
  4. washThe organic phase is washed with 0.2N hydrochloric acid (three times 100 ml) and water (200 ml)
  5. dry with materialdried over sodium sulphate
  6. concentrationconcentrated in a rotary evaporator

Sources & evidence

ORD record
ord-c643812049664b74a0b7ee37b1274bb3
Source dataset
uspto-grants-2011_12
Patent number
US08084604B2

Reaction notes

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