Hydrochloric Acid → HCID 22711148, compound

HRID 352936Notes

Reaction equation

HRID 352936 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[C:7]([S:12]([N:15]1[CH2:20][CH2:19][N:18]([C:21]3[N:26]=[CH:25][C:24]([C:27]4[CH:32]=[CH:31][N:30]=[CH:29][CH:28]=4)=[CH:23][N:22]=3)[CH:17]([CH2:33][C:34](OC)=[O:35])[CH2:16]1)(=[O:14])=[O:13])[CH:6]=[CH:5]2.[OH-:38].[Na+].O.Cl>O1CCCC1.CO.C(Cl)Cl.CO.C(O)C>[ClH:1].[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[C:7]([S:12]([N:15]1[CH2:20][CH2:19][N:18]([C:21]3[N:22]=[CH:23][C:24]([C:27]4[CH:32]=[CH:31][N:30]=[CH:29][CH:28]=4)=[CH:25][N:26]=3)[CH:17]([CH2:33][C:34]([N:15]3[CH2:20][CH2:19][O:38][CH2:17][CH2:16]3)=[O:35])[CH2:16]1)(=[O:13])=[O:14])[CH:6]=[CH:5]2

Participants

9

Reactant 4

HCID 313Hydrochloric Acid2×HCID 962WaterHCID 14798Sodium HydroxideHCID 22709679HCID 22709679, compound

Product 1

HCID 22711148HCID 22711148, compoundYield 34.3%

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 887MethanolSolventHCID 8028TetrahydrofuranSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

In tetrahydrofuran (10 ml) and methanol (5.0 ml) was dissolved 4-[(6-chloronaphthalen-2-yl)sulfonyl]-2-(methoxycarbonylmethyl)-1-[5-(pyridin-4-yl)pyrimidin-2-yl]piperazine (583 mg). Under ice cooling, a mixture of sodium hydroxide (200 mg) and water (1.0 ml) was added dropwise to the resulting solution under ice cooling, followed by stirring at room temperature for 5 hours. Under ice cooling, concentrated hydrochloric acid (420 μl) was added to the reaction mixture to make it weakly acidic. The reaction mixture was then distilled under reduced pressure. To the residue were added morpholine (102 μl), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (239 mg) and 1-hydroxybenzotriazole hydrate (159 mg). The resulting mixture was dissolved in N,N-dimethylformamide (60 ml) and methylene chloride (30 ml). Diisopropylethylamine (760 μl) was added dropwise to the resulting solution under ice cooling, followed by stirring at room temperature for 12.5 hours. The reaction mixture was distilled under reduced pressure. A 100% aqueous solution of citric acid was added to the residue and it was extracted with methylene chloride. The organic layer was washed with a saturated aqueous solution of sodium bicarbonate and saturated aqueous NaCl solution, dried over anhydrous sodium sulfate and distilled under reduced pressure to remove the solvent. The residue was subjected to column chromatography (10% methanol—methylene chloride) using as a carrier silica gel, followed by crystallization from methylene chloride-tetrahydrofuran, whereby a crudely purified product (349 mg) was obtained. A portion (161 mg) of then product was dissolved in methylene chloride-methanol. To the resulting solution was added 1N aqueous hydrochloride in ethanol (260 μl) and the mixture was concentrated to dryness. Ethyl acetate was added to the concentrate and the solid thus obtained was collected by filtration, washed with ethyl acetate and dried, whereby the title compound (117 mg) was obtained as colorless powder.

Workup

  1. additionwas added dropwise to the resulting solution under ice cooling
  2. distillationThe reaction mixture was then distilled under reduced pressure
  3. additionTo the residue were added morpholine (102 μl), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (239 mg) and 1-hydroxybenzotriazole hydrate (159 mg)
  4. dissolutionThe resulting mixture was dissolved in N,N-dimethylformamide (60 ml)
  5. additionDiisopropylethylamine (760 μl) was added dropwise to the resulting solution under ice cooling
  6. stirringby stirring at room temperature for 12.5 hours
  7. distillationThe reaction mixture was distilled under reduced pressure
  8. additionA 100% aqueous solution of citric acid was added to the residue and it
  9. extractionwas extracted with methylene chloride
  10. washThe organic layer was washed with a saturated aqueous solution of sodium bicarbonate and saturated aqueous NaCl solution
  11. dry with materialdried over anhydrous sodium sulfate
  12. distillationdistilled under reduced pressure
  13. customto remove the solvent
  14. customfollowed by crystallization from methylene chloride-tetrahydrofuran, whereby a crudely purified product (349 mg)
  15. customwas obtained
  16. concentrationthe mixture was concentrated to dryness
  17. additionEthyl acetate was added to the
  18. concentrationconcentrate
  19. customthe solid thus obtained
  20. filtrationwas collected by filtration
  21. washwashed with ethyl acetate
  22. customdried

Sources & evidence

ORD record
ord-c12bd8251e614f75ac22eee90164f7fa
Source dataset
uspto-grants-2004_06
Patent number
US06747023B1

Reaction notes

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