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

HRID 724226Notes

Reaction equation

HRID 724226 reaction equation
[CH:1](NC(C)C)([CH3:3])[CH3:2].[CH2:8]([Li])[CH2:9]CC.C(OCC)(=O)C.[CH:19]([N:22](C(C)C)[C:23]([C:25]1C=C[C:32]2[C:27](=C[CH:29]=[C:30]([C:35]([C:37]3[N:38]=[CH:39][N:40](C(C4C=CC=CC=4)(C4C=CC=CC=4)C4C=CC=CC=4)[CH:41]=3)=[O:36])[CH:31]=2)[CH:26]=1)=[O:24])(C)C>C1COCC1.O>[OH:36][C:35]1([C:30]2[CH:31]=[C:32]3[C:1](=[CH:3][CH:29]=2)[CH:2]=[C:25]([C:23]([NH:22][CH3:19])=[O:24])[CH:26]=[CH:27]3)[C:37]2[N:38]([CH:39]=[N:40][CH:41]=2)[CH2:9][CH2:8]1

Participants

7

Reactant 4

HCID 7912DiisopropylamineHCID 8857Ethyl AcetateHCID 21879613N,N-diisopropyl-6-[(1-trityl-1H-imidazol-4-yl)carbonyl]-2-naphthamideHCID 178418339Butyllithium

Product 1

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

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-70 °C

Procedure

Dry THF (600 ml) containing diisopropylamine (21.3 ml) was cooled to −70° C. and n-butyl lithium (1.6 M; 95.0 ml) was added dropwise. The mixture was stirred for 10 min and ethyl acetate (14.9 ml) was added dropwise. The mixture was stirred at the same temperature for 30 min. A solution of N,N-diisopropyl-6-[(1-trityl-1H-imidazol-4-yl)carbonyl]-2-naphthamide (60.0 g) in dry THF (150 ml) was added dropwise at −70° C. The mixture was stirred at the same temperature for 30 min and the reaction mixture was gradually warmed to −30° C. Water was added to stop the reaction. The organic layer was separated and the aqueous layer was extracted with a THF-toluene (1:1) mixture. The organic layers were combined, washed with saturated brine and dried over magnesium sulfate. The solvent was evaporated to give the title compound quantitatively as a pale yellow oil.

Workup

  1. stirringThe mixture was stirred at the same temperature for 30 min
  2. stirringThe mixture was stirred at the same temperature for 30 min
  3. temperaturethe reaction mixture was gradually warmed to −30° C
  4. customthe reaction
  5. customThe organic layer was separated
  6. extractionthe aqueous layer was extracted with a THF-toluene (1:1) mixture
  7. washwashed with saturated brine
  8. dry with materialdried over magnesium sulfate
  9. customThe solvent was evaporated

Sources & evidence

ORD record
ord-9e33f6d1aeae4927a2acf4fea78309bc
Source dataset
uspto-grants-2006_11
Patent number
US07141598B2

Reaction notes

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