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

HRID 724227Notes

Reaction equation

HRID 724227 reaction equation
CN.C([Li])CCC.[OH:8][C:9]1([C:17]2[CH:18]=[C:19]3[C:24](=[CH:25][CH:26]=2)[CH:23]=[C:22]([C:27]([N:29](C(C)C)[CH:30](C)C)=[O:28])[CH:21]=[CH:20]3)[C:16]2[N:12]([CH:13]=[N:14][CH:15]=2)[CH2:11][CH2:10]1.O>C1COCC1.[Cl-].[Na+].O.C(OCC)(=O)C>[OH:8][C:9]1([C:17]2[CH:18]=[C:19]3[C:24](=[CH:25][CH:26]=2)[CH:23]=[C:22]([C:27]([NH:29][CH3:30])=[O:28])[CH:21]=[CH:20]3)[C:16]2[N:12]([CH:13]=[N:14][CH:15]=2)[CH2:11][CH2:10]1

Participants

8

Reactant 4

HCID 962WaterHCID 6329MethylamineHCID 218796466-(7-hydroxy-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-7-yl)-N,N-diisopropyl-2-naphthamideHCID 178418339Butyllithium

Product 1

HCID 98830296-(7-hydroxy-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-7-yl)-N-methyl-2-naphthamideYield 72%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

Methylamine (2M in THF, 200 ml) was dissolved in dry THF (300 ml) and the mixture was cooled to −70° C. n-Butyl lithium (1.6 M; 250 ml) was added dropwise and the mixture was stirred at the same temperature for 20 min. The above-mentioned solution was added to a suspension (600 ml) of 6-(7-hydroxy-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-7-yl)-N,N-diisopropyl-2-naphthamide (37.7 g) in dry THF with a Teflon needle while stirring the mixture under ice-cooling, and the mixture was stirred at room temperature for 16 h. The saturated brine and water were added to the reaction mixture, and the mixture was diluted with ethyl acetate. The mixture was stirred for 10 min and the precipitated crystals were filtrated. The organic layer of the filtrate was separated and the aqueous layer was extracted with THF/ethyl acetate (1:1) mixture. The organic layers were combined and dried over sodium sulfate. The solvent was evaporated under reduced pressure and the residue was dissolved in THF-ethyl acetate (1:1). The precipitated crystals were collected by filtration to give colorless powder crystals. The obtained crystals were combined and recrystallized from ethanol-ethyl acetate to give the title compound (22.1 g) as colorless powder crystals.

Workup

  1. additionwas added dropwise
  2. stirringwhile stirring the mixture under ice-
  3. temperaturecooling
  4. stirringthe mixture was stirred at room temperature for 16 h
  5. stirringThe mixture was stirred for 10 min
  6. filtrationthe precipitated crystals were filtrated
  7. customThe organic layer of the filtrate was separated
  8. extractionthe aqueous layer was extracted with THF/ethyl acetate (1:1) mixture
  9. dry with materialdried over sodium sulfate
  10. customThe solvent was evaporated under reduced pressure
  11. dissolutionthe residue was dissolved in THF-ethyl acetate (1:1)
  12. filtrationThe precipitated crystals were collected by filtration
  13. customto give colorless powder crystals
  14. customrecrystallized from ethanol-ethyl acetate

Sources & evidence

ORD record
ord-5cc632587798421186b5435364e0647c
Source dataset
uspto-grants-2006_11
Patent number
US07141598B2

Reaction notes

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