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

HRID 724224Notes

Reaction equation

HRID 724224 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[C:7]([C:12]([OH:14])=O)[CH:6]=[CH:5]2.CCCCCC.C([Li])CCC.[CH:26]1[N:30]=[CH:29][N:28]2[CH2:31][CH2:32][C:33](=[O:34])[C:27]=12.[Cl-].[NH4+:36]>C1COCC1.C(OCC)(=O)C>[OH:34][C:33]1([C:2]2[CH:3]=[C:4]3[C:9](=[CH:10][CH:11]=2)[CH:8]=[C:7]([C:12]([NH2:36])=[O:14])[CH:6]=[CH:5]3)[C:27]2[N:28]([CH:29]=[N:30][CH:26]=2)[CH2:31][CH2:32]1

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 45498526-Bromo-2-naphthalenecarboxylic acidHCID 111709605,6-Dihydropyrrolo[1,2-c]imidazol-7-oneHCID 178418244HCID 178418244, compound

Product 1

HCID 99658856-(7-hydroxy-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-7-yl)-2-naphthamide

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-100 °C

Procedure

6-Bromo-2-naphthoic acid (1.51 g) was dissolved in dry THF (50 ml) and the mixture was cooled in a liquid nitrogen/diethyl ether bath to −100° C. With stirring the mixture, an n-butyl lithium hexane solution (1.6M; 7.88 ml) was added dropwise at not more than −95° C. over 5 min. The mixture was stirred at −100° C. for 30 min and at −80° C. for 10 min. Thereafter, the mixture was cooled again to −100° C. and a solution of 5,6-dihydro-7H-pyrrolo[1,2-c]imidazol-7-one (0.61 g) in dry THF (11 ml) was added dropwise at not more than −90° C. over 5 min. The mixture was stirred at same temperature for 30 min and warmed to −70° C. over 30 min. A saturated aqueous ammonium chloride solution (25 ml) was added to stop the reaction. After stirring the mixture for 10 min, ethyl acetate (50 ml) was added for partitioning. The organic layer was removed and the aqueous layer was concentrated to dryness. The resulting residue was purified by flash column chromatography and the objective fraction was dissolved in methanol. This solution was concentrated, ether was added to the precipitated powder for filtration and dried to give the title compound (180 mg) as a colorless powder. The mother liquid was concentrated to give a residue (449 mg) containing the title compound.

Workup

  1. stirringThe mixture was stirred at −100° C. for 30 min and at −80° C. for 10 min
  2. temperatureThereafter, the mixture was cooled again to −100° C.
  3. stirringThe mixture was stirred at same temperature for 30 min
  4. temperaturewarmed to −70° C. over 30 min
  5. customthe reaction
  6. stirringAfter stirring the mixture for 10 min
  7. customfor partitioning
  8. customThe organic layer was removed
  9. concentrationthe aqueous layer was concentrated to dryness
  10. customThe resulting residue was purified by flash column chromatography
  11. dissolutionthe objective fraction was dissolved in methanol
  12. concentrationThis solution was concentrated
  13. additionether was added to the precipitated powder for filtration
  14. customdried

Sources & evidence

ORD record
ord-c4b6bc25174f4413872ba539fd6ac6fe
Source dataset
uspto-grants-2006_11
Patent number
US07141598B2

Reaction notes

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