HCID 59455298, compound → HCID 178422186, compound

HRID 2389393Notes

Reaction equation

HRID 2389393 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:10]=[C:11]3[C:15](=[CH:16][CH:17]=2)[N:14]([C:18]2[N:22]=[CH:21][N:20](C(C4C=CC=CC=4)(C4C=CC=CC=4)C4C=CC=CC=4)[N:19]=2)[C:13](=[O:42])[C:12]3([CH3:50])[CH2:43][C:44]2[CH:45]=[N:46][CH:47]=[N:48][CH:49]=2)[CH:5]=[CH:6][C:7]=1[F:8]>CO.ClCCl.Cl>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:10]=[C:11]3[C:15](=[CH:16][CH:17]=2)[N:14]([C:18]2[N:22]=[CH:21][NH:20][N:19]=2)[C:13](=[O:42])[C:12]3([CH3:50])[CH2:43][C:44]2[CH:49]=[N:48][CH:47]=[N:46][CH:45]=2)[CH:5]=[CH:6][C:7]=1[F:8]

Participants

5

Reactant 1

HCID 59455298HCID 59455298, compound

Product 1

HCID 178422186HCID 178422186, compound

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

5-(3-chloro-4-fluorophenyl)-3-methyl-3-(pyrimidin-5-ylmethyl)-1-(1-trityl-1,2,4-triazol-3-yl)-1,3-dihydro-2H-indol-2-one (8.25 g, 12.2 mmol) in methanol (60 mL), dichloromethane (10 mL) and 1 N aqueous HCl solution (30 mL) was stirred at 50° C. for 1.5 hours. Most of the solvent was removed under reduced pressure. The residue was dissolved in dichloromethane and water (50 mL) was added. The pH of the mixture was adjusted to pH=7 with the addition of 1 N aqueous sodium hydroxide solution. The organic layer was separated and the aqueous layer further extracted with dichloromethane (2×100 mL). The organic extracts were combined, dried (MgSO4), filtered and concentrated under reduced pressure. The residue was dissolved in dichloromethane and hexane was then slowly added. The product recrystallized over 3 days. The crystalline product was filtered, washed with 50% dichloromethane/hexanes and dried under reduced pressure. The filtrate was collected, concentrated under reduced pressure and purified by column chromatography on silica gel Biotage 40S, eluting with 40-100% ethyl acetate/hexanes, to give additional product. The product from crystallization and the product from column chromatography were combined, dissolved in acetonitrile/water and lyophilized to afford 5-(3-chloro-4-fluorophenyl)-3-methyl-3-(pyrimidin-5-ylmethyl)-1-(1H-1,2,4-triazol-3-yl)-1,3-dihydro-2H-indol-2-one as a white solid.

Workup

  1. customMost of the solvent was removed under reduced pressure
  2. dissolutionThe residue was dissolved in dichloromethane
  3. additionwater (50 mL) was added
  4. additionThe pH of the mixture was adjusted to pH=7 with the addition of 1 N aqueous sodium hydroxide solution
  5. customThe organic layer was separated
  6. extractionthe aqueous layer further extracted with dichloromethane (2×100 mL)
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. dissolutionThe residue was dissolved in dichloromethane
  11. additionhexane was then slowly added
  12. customThe product recrystallized over 3 days
  13. filtrationThe crystalline product was filtered
  14. washwashed with 50% dichloromethane/hexanes
  15. customdried under reduced pressure
  16. customThe filtrate was collected
  17. concentrationconcentrated under reduced pressure
  18. custompurified by column chromatography on silica gel Biotage 40S
  19. washeluting with 40-100% ethyl acetate/hexanes
  20. customto give additional product
  21. customThe product from crystallization
  22. dissolutiondissolved in acetonitrile/water

Sources & evidence

ORD record
ord-070f88fe01db4fc3b48734098d727121
Source dataset
uspto-grants-2012_09
Patent number
US08273749B2

Reaction notes

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