1H-1,2,4-Triazole → 1-{[(R)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-5-(4-1,2,4-triazol-1-yl-benzyl)-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-carbonyl]-amino}-cyclopropanecarboxylic acid allyl ester

HRID 1040567Notes

Reaction equation

HRID 1040567 reaction equation
[CH2:1]([O:4][C:5]([C:7]1([NH:10][C:11]([C:13]2[N:17]3[C@@:18]([CH2:31][C:32]4[CH:37]=[CH:36][C:35](I)=[CH:34][CH:33]=4)([CH3:30])[C:19](=[O:29])[N:20]([C:21]4[CH:26]=[C:25]([Cl:27])[CH:24]=[C:23]([Cl:28])[CH:22]=4)[C:16]3=[N:15][CH:14]=2)=[O:12])[CH2:9][CH2:8]1)=[O:6])[CH:2]=[CH2:3].[NH:39]1[CH:43]=[N:42][CH:41]=[N:40]1.CN[C@@H]1CCCC[C@H]1NC.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C>[CH2:1]([O:4][C:5]([C:7]1([NH:10][C:11]([C:13]2[N:17]3[C@:18]([CH3:30])([CH2:31][C:32]4[CH:37]=[CH:36][C:35]([N:39]5[CH:43]=[N:42][CH:41]=[N:40]5)=[CH:34][CH:33]=4)[C:19](=[O:29])[N:20]([C:21]4[CH:26]=[C:25]([Cl:27])[CH:24]=[C:23]([Cl:28])[CH:22]=4)[C:16]3=[N:15][CH:14]=2)=[O:12])[CH2:9][CH2:8]1)=[O:6])[CH:2]=[CH2:3]

Participants

6

Reactant 4

HCID 92571H-1,2,4-TriazoleHCID 62657Potassium Phosphate, TribasicHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 584309951-{[(R)-7-(3,5-dichloro-phenyl)-5-(4-iodo-benzyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-carbonyl]-amino}-cyclopropanecarboxylic acid allyl ester

Product 1

HCID 584310531-{[(R)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-5-(4-1,2,4-triazol-1-yl-benzyl)-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-carbonyl]-amino}-cyclopropanecarboxylic acid allyl esterYield 48%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

An 8-mL vial was charged with 1-{[(R)-7-(3,5-dichloro-phenyl)-5-(4-iodo-benzyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-carbonyl]-amino}-cyclopropanecarboxylic acid allyl ester (251 mg, 0.377 mmol), 1,2,4-triazole (39 mg, 0.57 mmol), and (1R,2R)—N,N′-dimethyl-cyclohexane-1,2-diamine (16 mg, 0.11 mmol), K3PO4 (160 mg, 0.76 mmol), and 0.5 mL of DMF. The vial was purged with N2 and sealed with a screw cap. The green reaction mixture was heated at reflux for 20 h. The reaction mixture was cooled to room temperature, diluted with 3 mL of EtOAc, and filtered through a small plug of Celite, washing with 20 mL of ethyl acetate. The filtrates were washed with 3×10 mL of water and 10 mL of brine, dried over Na2SO4, filtered, and concentrated. The crude was purified by flash chromatography on silica gel (20 g, 0-3% MeOH/CH2Cl2) to provide 109 mg (48%) of 1-{[(R)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-5-(4-1,2,4-triazol-1-yl-benzyl)-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-carbonyl]-amino}-cyclopropanecarboxylic acid allyl ester as a pale orange foam.

Workup

  1. customThe vial was purged with N2
  2. customsealed with a screw
  3. customcap
  4. temperatureThe green reaction mixture was heated
  5. temperatureat reflux for 20 h
  6. additiondiluted with 3 mL of EtOAc
  7. filtrationfiltered through a small plug of Celite
  8. washwashing with 20 mL of ethyl acetate
  9. washThe filtrates were washed with 3×10 mL of water and 10 mL of brine
  10. dry with materialdried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe crude was purified by flash chromatography on silica gel (20 g, 0-3% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-fe0cdc9473a24bf0997da6f48bd2b2b1
Source dataset
uspto-grants-2013_10
Patent number
US08552205B2

Reaction notes

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