4-Methylmorpholine → 4-[2-(2,2,2-Trifluoroethyl)guanidino]-2-[5-(2-benzyloxycarbonylaminoacetylamino)pentyl]pyrimidine

HRID 1462344Notes

Reaction equation

HRID 1462344 reaction equation
[CH2:1]([O:8][C:9]([NH:11][CH2:12][C:13]([OH:15])=O)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN1CCOCC1.ClC(OCC(C)C)=O.[F:31][C:32]([F:51])([F:50])[CH2:33][N:34]=[C:35]([NH2:49])[NH:36][C:37]1[CH:42]=[CH:41][N:40]=[C:39]([CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][NH2:48])[N:38]=1>C1COCC1>[F:51][C:32]([F:31])([F:50])[CH2:33][N:34]=[C:35]([NH2:49])[NH:36][C:37]1[CH:42]=[CH:41][N:40]=[C:39]([CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][NH:48][C:13](=[O:15])[CH2:12][NH:11][C:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[O:10])[N:38]=1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 14349BenzyloxycarbonylglycineHCID 62365Isobutyl chloroformateHCID 202086774-[2-(2,2,2-Trifluoroethyl)guanidino]-2-(5-aminopentyl)pyrimidine

Product 1

HCID 202469454-[2-(2,2,2-Trifluoroethyl)guanidino]-2-[5-(2-benzyloxycarbonylaminoacetylamino)pentyl]pyrimidineYield 34.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of N-benzyloxycarbonylglycine (0.21 g.) in freshly distilled THF (5 ml.) was added N-methylmorpholine (0.1 g.). The resulting solution was stirred with cooling in an ice-salt bath, and a solution of i-butyl chloroformate (0.136 g.) in a small volume of THF was added in one portion. A precipitate formed immediately, and the mixture was stirred with cooling for 5 minutes. A solution of 4-[2-(2,2,2-trifluoroethyl)guanidino]-2-(5-aminopentyl)pyrimidine (0.35 g.) in THF (10 ml.) was gradually added. The mixture was stirred at room temperature for 2 hours, then evaporated in vacuo. Sodium bicarbonate solution was added to the residue and the mixture extracted with EtOAc. The extract was dried (MgSO4) and evaporated to give a pale yellow oil which was purified by medium pressure chromatography, eluting with 5% v/v MeOH in methylene chloride to give 4-[2-(2,2,2-trifluoroethyl)guanidino]-2-[5-(2-benzyloxycarbonylaminoacetylamino)pentyl]pyrimidine (0.17 g.) which was used without further purification.

Workup

  1. temperaturewith cooling in an ice-salt bath
  2. customA precipitate formed immediately
  3. stirringthe mixture was stirred
  4. temperaturewith cooling for 5 minutes
  5. stirringThe mixture was stirred at room temperature for 2 hours
  6. customevaporated in vacuo
  7. additionSodium bicarbonate solution was added to the residue
  8. extractionthe mixture extracted with EtOAc
  9. dry with materialThe extract was dried (MgSO4)
  10. customevaporated
  11. customto give a pale yellow oil which
  12. customwas purified by medium pressure chromatography
  13. washeluting with 5% v/v MeOH in methylene chloride

Sources & evidence

ORD record
ord-5a4c480a15254e27aeb38adf952d6138
Source dataset
uspto-grants-1984_07
Patent number
US04460584

Reaction notes

Loading…