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

HRID 724222Notes

Reaction equation

HRID 724222 reaction equation
CCCCCC.C([Li])CCC.Br[C:13]1[CH:14]=[C:15]2[C:20](=[CH:21][CH:22]=1)[CH:19]=[C:18]([C:23]([NH:25][CH3:26])=[O:24])[CH:17]=[CH:16]2.[CH:27]1[N:31]=[CH:30][N:29]2[CH2:32][CH2:33][C:34](=[O:35])[C:28]=12.[Cl-].[NH4+]>C1COCC1>[OH:35][C:34]1([C:13]2[CH:14]=[C:15]3[C:20](=[CH:21][CH:22]=2)[CH:19]=[C:18]([C:23]([NH:25][CH3:26])=[O:24])[CH:17]=[CH:16]3)[C:28]2[N:29]([CH:30]=[N:31][CH:27]=2)[CH2:32][CH2:33]1

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 111709605,6-Dihydropyrrolo[1,2-c]imidazol-7-oneHCID 218796286-bromo-N-methyl-2-naphtamideHCID 178418244HCID 178418244, compound

Product 1

HCID 98830296-(7-hydroxy-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-7-yl)-N-methyl-2-naphthamideYield 36.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

Dry THF (150 ml) was cooled to −65° C. in a dry ice-acetone bath under an argon atmosphere and n-butyl lithium hexane solution (1.6M: 45.2 ml) was added. A solution of 6-bromo-N-methyl-2-naphthamide (8.68 g) in dry THF (700 ml) cooled to 10° C. was added to this solution at not more than −55° C., and the mixture was stirred for 1 h. A dry THF solution (60 ml) of 5,6-dihydro-7H-pyrrolo[1,2-c]imidazol-7-one (3.65 g) was added dropwise. The mixture was stirred at the same temperature for 1.5 h and saturated aqueous ammonium chloride solution (120 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 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 (3.36 g) as colorless crystals.

Workup

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

Sources & evidence

ORD record
ord-28985f74748d4ea9a0a9af6c222d686d
Source dataset
uspto-grants-2006_11
Patent number
US07141598B2

Reaction notes

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