Hydrochloric Acid → HCID 136375770, compound

HRID 869240Notes

Reaction equation

HRID 869240 reaction equation
Cl[C:2]1[C:7]([C:8]([NH2:10])=[O:9])=[C:6]([NH:11][C:12]2[CH:13]=[N:14][CH:15]=[C:16]([CH3:18])[CH:17]=2)[N:5]=[C:4]([S:19][CH3:20])[N:3]=1.C([O-])(=[O:23])C.[Na+].[OH-].[Na+].Cl>C1COCC1.CO.C(O)C.O.C(OCC)(=O)C.CN(C=O)C>[CH3:18][C:16]1[CH:17]=[C:12]([NH:11][C:6]2[N:5]=[C:4]([S:19][CH3:20])[NH:3][C:2](=[O:23])[C:7]=2[C:8]([NH2:10])=[O:9])[CH:13]=[N:14][CH:15]=1

Participants

11

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 517045Sodium AcetateHCID 86662047HCID 86662047, compound

Product 1

HCID 136375770HCID 136375770, compoundYield 14.8%

Reagents, catalysts & solvents 6

HCID 702EthanolSolventHCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of 4-chloro-6-[(5-methylpyridin-3-yl)amino]-2-(methylsulfanyl)pyrimidine-5-carboxamide (Preparation Example 359) (194 mg) and DMF (5 mL), sodium acetate (257 mg) was added and stirred at 100° C. for 5 hours. After the reaction liquid was cooled, ethyl acetate and water were added, and the precipitated powder was collected by filtration and dried to give a light yellow solid. To a mixture of the solid, ethanol (5 mL), methanol (20 mL) and THF (5 mL), 1M aqueous sodium hydroxide (3 mL) was added and stirred at room temperature for 1 hour, at 60° C. for 1 hour, and at 80° C. for 1 hour. After the reaction liquid was cooled, 1M hydrochloric acid (3 mL) was added, and the reaction liquid was extracted with chloroform-isopropanol. Silica gel was added to the organic layer, and the solvent was distilled off, followed by purification by silica gel column chromatography (eluent; chloroform:methanol=100:0 to 20:1) to give a crude product. This crude product was washed with a small amount of methanol to give 4-[(5-methylpyridin-3-yl)amino]-2-(methylsulfanyl)-6-oxo-1,6-dihydropyrimidine-5-carboxamide (27 mg) as a yellow solid.

Workup

  1. additionwas added
  2. customAfter the reaction liquid
  3. temperaturewas cooled
  4. filtrationthe precipitated powder was collected by filtration
  5. customdried
  6. customto give a light yellow solid
  7. additionwas added
  8. stirringstirred at room temperature for 1 hour, at 60° C. for 1 hour
  9. waitat 80° C. for 1 hour
  10. customAfter the reaction liquid
  11. temperaturewas cooled
  12. customthe reaction liquid
  13. extractionwas extracted with chloroform-isopropanol
  14. additionSilica gel was added to the organic layer
  15. distillationthe solvent was distilled off
  16. customfollowed by purification by silica gel column chromatography (eluent; chloroform:methanol=100:0 to 20:1)
  17. customto give a crude product
  18. washThis crude product was washed with a small amount of methanol

Sources & evidence

ORD record
ord-1f916b5ba370453baf0902e6b6c2cc46
Source dataset
uspto-grants-2015_03
Patent number
US08969336B2

Reaction notes

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