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

HRID 542488Notes

Reaction equation

HRID 542488 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 2N aqueous HCl. The acid layer was basified with 11N 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 2N 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-da3965f4a61a4f13bdb685ec961ddfa3
Source dataset
uspto-grants-1987_04
Patent number
US04657908

Reaction notes

Loading…