Dimethylformamide → N-[5-(4-[2-(2,2,2-trifluoroethyl)guanidino]pyrimid-2-yl)pentyl]-3-(imidazol-4-yl)propionamide bis maleate hemihydrate

HRID 2413199Notes

Reaction equation

HRID 2413199 reaction equation
ClC([O:4][CH2:5][CH3:6])=[O:3].[NH:7]1[CH:11]=[C:10]([CH2:12][CH2:13][C:14]([OH:16])=[O:15])[N:9]=[CH:8]1.C(N(CC)CC)C.[F:24][C:25]([F:44])([F:43])[CH2:26][N:27]=[C:28]([NH2:42])[NH:29][C:30]1[CH:35]=[CH:34][N:33]=[C:32]([CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][NH2:41])[N:31]=1.CN([CH:48]=[O:49])C>>[OH2:3].[C:5]([OH:4])(=[O:49])/[CH:6]=[CH:13]\[C:14]([OH:16])=[O:15].[C:48]([OH:49])(=[O:3])/[CH:12]=[CH:13]\[C:14]([OH:16])=[O:15].[F:44][C:25]([F:24])([F:43])[CH2:26][N:27]=[C:28]([NH2:42])[NH:29][C:30]1[CH:35]=[CH:34][N:33]=[C:32]([CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][NH:41][C:14](=[O:16])[CH2:13][CH2:12][C:10]2[N:9]=[CH:8][NH:7][CH:11]=2)[N:31]=1.[F:44][C:25]([F:24])([F:43])[CH2:26][N:27]=[C:28]([NH2:42])[NH:29][C:30]1[CH:35]=[CH:34][N:33]=[C:32]([CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][NH:41][C:14](=[O:16])[CH2:13][CH2:12][C:10]2[N:9]=[CH:8][NH:7][CH:11]=2)[N:31]=1.[C:5]([OH:4])(=[O:49])/[CH:6]=[CH:13]\[C:14]([OH:16])=[O:15].[C:5]([OH:4])(=[O:49])/[CH:6]=[CH:13]\[C:14]([OH:16])=[O:15]

Participants

6

Reactant 5

HCID 6228Dimethylformamide2×HCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 202086774-[2-(2,2,2-Trifluoroethyl)guanidino]-2-(5-aminopentyl)pyrimidineHCID 178525356HCID 178525356, compound

Product 1

HCID 178512205N-[5-(4-[2-(2,2,2-trifluoroethyl)guanidino]pyrimid-2-yl)pentyl]-3-(imidazol-4-yl)propionamide bis maleate hemihydrate

Procedure

Ethyl chloroformate (0.14 ml.) was added to a stirred mixture of 3-(imidazol-4-yl)propionic acid (0.3 g.) and triethylamine (2 ml.) in DMF (5 ml.) at 0° and the mixture stirred at 0° for 0.5 hours. 4-[2-(2,2,2-Trifluoroethyl)guanidino]-2-(5-aminopentyl)pyrimidine (0.3 g.) in DMF (2 ml.) was added to the mixture and stirring was continued at room temperature for 16 hours. The mixture was evaporated and the residue partitioned between EtOAc and 2 N aqueous HCl. The acid layer was basified with 11 N aqueous NaOH, extracted with EtOAc, dried (MgSO4) and evaporated to dryness. The residual gum was dissolved in EtOAc and treated with excess of a solution of maleic acid in EtOAc. The resulting solid was filtered and recrystallised from EtOH/EtOAc to give N-[5-(4-[2-(2,2,2-trifluoroethyl)guanidino]pyrimid-2-yl)pentyl]-3-(imidazol-4-yl)propionamide bis maleate hemihydrate (containing 0.5 EtOH of crystallisation) (0.2 g.), m.p. 136°-141° (decomp.).

Workup

  1. stirringstirring
  2. waitwas continued at room temperature for 16 hours
  3. customThe mixture was evaporated
  4. customthe residue partitioned between EtOAc and 2 N aqueous HCl
  5. extractionextracted with EtOAc
  6. dry with materialdried (MgSO4)
  7. customevaporated to dryness
  8. dissolutionThe residual gum was dissolved in EtOAc
  9. additiontreated with excess of a solution of maleic acid in EtOAc
  10. filtrationThe resulting solid was filtered
  11. customrecrystallised from EtOH/EtOAc

Sources & evidence

ORD record
ord-bd2c05f0aa0c4aa8b5265f01aa05792e
Source dataset
uspto-grants-1985_01
Patent number
US04496571

Reaction notes

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