Ethyl Acetoacetate → 1-[2-[4-(6-methyl-4-oxo-1H-pyrimidin-2-yl)butoxy]pyrimidin-4-yl]-2-(2,2,2-trifluoroethyl)guanidine

HRID 2291323Notes

Reaction equation

HRID 2291323 reaction equation
Cl.[F:2][C:3]([F:24])([F:23])[CH2:4][N:5]=[C:6]([NH2:22])[NH:7][C:8]1[CH:13]=[CH:12][N:11]=[C:10]([O:14][CH2:15][CH2:16][CH2:17][CH2:18][C:19]([NH2:21])=[NH:20])[N:9]=1.[C:25](OCC)(=[O:30])[CH2:26][C:27]([CH3:29])=O.[H-].[Na+]>CO>[OH:30][C:25]1[CH:26]=[C:27]([CH3:29])[N:21]=[C:19]([CH2:18][CH2:17][CH2:16][CH2:15][O:14][C:10]2[N:9]=[C:8]([NH:7][C:6]([NH2:22])=[N:5][CH2:4][C:3]([F:2])([F:23])[F:24])[CH:13]=[CH:12][N:11]=2)[N:20]=1

Participants

5

Reactant 3

HCID 8868Ethyl AcetoacetateHCID 24758Sodium hydrideHCID 212797305-(4-[2-(2,2,2-Trifluoroethyl)guanidino]pyrimid-2-yloxy)valeramidine hydrochloride

Product 1

HCID 1784293291-[2-[4-(6-methyl-4-oxo-1H-pyrimidin-2-yl)butoxy]pyrimidin-4-yl]-2-(2,2,2-trifluoroethyl)guanidine

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

5-(4-[2-(2,2,2-Trifluoroethyl)guanidino]pyrimid-2-yloxy)valeramidine hydrochloride (0.5 g.) was added to a solution of ethyl acetoacetate (0.352 g.) and sodium hydride (0.07 g.) in MeOH (6 ml.). The resulting solution was heated under reflux for 18 hours. The solvent was evaporated and the residue taken up in aqueous HOAc and extracted with EtOAc. The aqueous layer was basified with potassium carbonate and extracted with EtOAc. Work up gave a sticky solid which was crystallised from acetonitrile to give 4-hydroxy-6-methyl-2-[4-(4-[2-(2,2,2-trifluoroethyl)guanidino]pyrimid-2-yloxy)butyl]pyrimidine as white crystals (0.22 g.), m.p. 191°-193°.

Workup

  1. temperatureThe resulting solution was heated
  2. temperatureunder reflux for 18 hours
  3. customThe solvent was evaporated
  4. extractionextracted with EtOAc
  5. extractionextracted with EtOAc
  6. customWork up gave a sticky solid which
  7. customwas crystallised from acetonitrile

Sources & evidence

ORD record
ord-d59c1714b7d948489e92c494d080fd47
Source dataset
uspto-grants-1989_01
Patent number
US04795755

Reaction notes

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