Hydroxylamine → 1-(2,2-Dimethoxyethyl)-1,6-dihydro-N-hydroxy-6-oxo-2-phenyl-5-pyrimidinecarboxamide

HRID 1862069Notes

Reaction equation

HRID 1862069 reaction equation
C(N(CC)CC)C.[CH3:8][O:9][CH:10]([O:28][CH3:29])[CH2:11][N:12]1[C:17](=[O:18])[C:16]([C:19](O)=[O:20])=[CH:15][N:14]=[C:13]1[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.C(Cl)(=O)OCC(C)C.[NH2:38][OH:39]>O1CCCC1>[OH:39][NH:38][C:19]([C:16]1[C:17](=[O:18])[N:12]([CH2:11][CH:10]([O:28][CH3:29])[O:9][CH3:8])[C:13]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[N:14][CH:15]=1)=[O:20]

Participants

6

Reactant 4

HCID 787HydroxylamineHCID 8471TriethylamineHCID 62365Isobutyl chloroformateHCID 117225541-(2,2-Dimethoxyethyl)-6-oxo-2-phenyl-1,6-dihydropyrimidine-5-carboxylic acid

Product 1

HCID 97970941-(2,2-Dimethoxyethyl)-1,6-dihydro-N-hydroxy-6-oxo-2-phenyl-5-pyrimidinecarboxamideYield 91%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Triethylamine (49.4 ml) was added to a solution of 1-(2,2-dimethoxyethyl)-6-oxo-2-phenyl-1,6-dihydropyrimidin-5-ylcarboxylic acid (97.3 g) in tetrahydrofuran (800 ml) in an ice bath in an argon atmosphere, and isobutyl chlorocarbonate (45.6 ml) was added dropwise thereto at 5° C. or lower, followed by stirring at the same temperature for 1 hour. To the reaction mixture was added a 50% hydroxylamine aqueous solution (422 ml), followed by stirring for 20 minutes. The reaction mixture was separated to layers. The aqueous layer was extracted with ethyl acetate (200 ml). The organic layers were combined, washed with saturated saline (200 ml), and concentrated. To the residue was added toluene (200 ml), followed by concentration. The resulting crude crystals were washed with isopropyl ether (1000 ml) by heating under reflux for 10 minutes, cooled to room temperature, and crystals were collected by filtration. The collected crystals were dried in vacuo at room temperature overnight to obtain the title compound (93.3 g; yield: 91%) having the following physical properties.

Workup

  1. additionwas added dropwise
  2. customat 5° C.
  3. stirringby stirring for 20 minutes
  4. customThe reaction mixture was separated to layers
  5. extractionThe aqueous layer was extracted with ethyl acetate (200 ml)
  6. washwashed with saturated saline (200 ml)
  7. concentrationconcentrated
  8. additionTo the residue was added toluene (200 ml)
  9. concentrationfollowed by concentration
  10. washThe resulting crude crystals were washed with isopropyl ether (1000 ml)
  11. temperatureby heating
  12. temperatureunder reflux for 10 minutes
  13. filtrationcrystals were collected by filtration
  14. customThe collected crystals were dried in vacuo at room temperature overnight

Sources & evidence

ORD record
ord-c06fee7a81ca4632ab966d2e788c6a59
Source dataset
uspto-grants-2003_03
Patent number
US06534658B1

Reaction notes

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