Benzene, 1-bromo-2-(trifluoromethyl)- → 6-(7-hydroxy-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-7-yl)-N-methyl-2-naphthamide

HRID 724223Notes

Reaction equation

HRID 724223 reaction equation
BrC1C=CC=CC=1C(F)(F)F.CCCCCC.C([Li])CCC.Br[C:24]1[CH:25]=[C:26]2[C:31](=[CH:32][CH:33]=1)[CH:30]=[C:29]([C:34]([NH:36][CH3:37])=[O:35])[CH:28]=[CH:27]2.[CH:38]1[N:42]=[CH:41][N:40]2[CH2:43][CH2:44][C:45](=[O:46])[C:39]=12.[Cl-].[NH4+]>C1COCC1>[OH:46][C:45]1([C:24]2[CH:25]=[C:26]3[C:31](=[CH:32][CH:33]=2)[CH:30]=[C:29]([C:34]([NH:36][CH3:37])=[O:35])[CH:28]=[CH:27]3)[C:39]2[N:40]([CH:41]=[N:42][CH:38]=2)[CH2:43][CH2:44]1

Participants

7

Reactant 5

HCID 9806Benzene, 1-bromo-2-(trifluoromethyl)-HCID 25517Ammonium ChlorideHCID 111709605,6-Dihydropyrrolo[1,2-c]imidazol-7-oneHCID 218796286-bromo-N-methyl-2-naphtamideHCID 178418244HCID 178418244, compound2×

Product 1

HCID 98830296-(7-hydroxy-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-7-yl)-N-methyl-2-naphthamideYield 44.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-65 °C

Procedure

Under an argon atmosphere, 2-bromobenzotrifluoride (33.05 g) was dissolved in dry THF (600 ml), and the mixture was cooled to −65° C. in a dry ice-acetone bath. An n-butyl lithium hexane solution (1.6M: 93.7 ml) was added with stirring and the mixture was stirred at the same temperature for 30 min. After stirring the mixture, a dry THF (2.88L) solution of 6-bromo-N-methyl-2-naphthamide (38.03 g) cooled to 10° C. was added at not more than −55° C. The mixture was stirred for 20 min. An n-butyl lithium hexane solution (1.6M: 94.5 ml) was added at not more than −65° C. The mixture was stirred for 30 min and 5,6-dihydro-7H-pyrrolo[1,2-c]imidazol-7-one (14.66 g) in a dry THF solution (240 ml) was added dropwise. The mixture was stirred at the same temperature for 1.5 h and saturated aqueous ammonium chloride solution (520 ml) was added to stop the reaction. The solvent was evaporated under reduced pressure and an ethanol-soluble material was extracted from the resulting residue and the solvent was evaporated again. The resulting residue was purified by flash silica gel column chromatography (eluent; chloroform/methanol containing ammonia (7%); 19/1→9/1). The eluate was recrystallized from methanol to give the title compound (16.44 g) as colorless crystals. The physical and chemical data were identical with those of the compound obtained in Example 5.

Workup

  1. stirringthe mixture was stirred at the same temperature for 30 min
  2. stirringAfter stirring the mixture
  3. additionwas added at not more than −55° C
  4. stirringThe mixture was stirred for 20 min
  5. stirringThe mixture was stirred for 30 min
  6. stirringThe mixture was stirred at the same temperature for 1.5 h
  7. customthe reaction
  8. customThe solvent was evaporated under reduced pressure
  9. extractionan ethanol-soluble material was extracted from the resulting residue
  10. customthe solvent was evaporated again
  11. customThe resulting residue was purified by flash silica gel column chromatography (eluent; chloroform/methanol containing ammonia (7%); 19/1→9/1)
  12. customThe eluate was recrystallized from methanol

Sources & evidence

ORD record
ord-64d629f8d9b14edeaba1ea834d6146a4
Source dataset
uspto-grants-2006_11
Patent number
US07141598B2

Reaction notes

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