Potassium Iodide → 2-tert-Butyl-4-{4-[3-(4-methyl-5-cyclopropyl-4H-[1,2,4]triazol-3-ylsulfanyl)-propyl]-piperazin-1-yl}-6-cyclobutyl-pyrimidine fumarate

HRID 219749Notes

Reaction equation

HRID 219749 reaction equation
[C:1]([C:5]1[N:10]=[C:9]([N:11]2[CH2:16][CH2:15][N:14]([CH2:17][CH2:18][CH2:19]Cl)[CH2:13][CH2:12]2)[CH:8]=[C:7]([CH:21]2[CH2:24][CH2:23][CH2:22]2)[N:6]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:25][N:26]1[C:30]([CH:31]2[CH2:33][CH2:32]2)=[N:29][N:28]=[C:27]1[SH:34].[I-].[K+].[C:37]([OH:44])(=[O:43])/[CH:38]=[CH:39]/[C:40]([OH:42])=[O:41]>CN(C)C=O.C(OCC)(=O)C.O>[C:37]([OH:44])(=[O:43])/[CH:38]=[CH:39]/[C:40]([OH:42])=[O:41].[C:1]([C:5]1[N:10]=[C:9]([N:11]2[CH2:16][CH2:15][N:14]([CH2:17][CH2:18][CH2:19][S:34][C:27]3[N:26]([CH3:25])[C:30]([CH:31]4[CH2:33][CH2:32]4)=[N:29][N:28]=3)[CH2:13][CH2:12]2)[CH:8]=[C:7]([CH:21]2[CH2:24][CH2:23][CH2:22]2)[N:6]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 4875Potassium IodideHCID 444972Fumaric AcidHCID 666731042-tert-Butyl-4-[4-(3-chloro-propyl)-piperazin-1-yl]-6-cyclobutyl-pyrimidineHCID 178481681HCID 178481681, compound

Product 1

HCID 690275872-tert-Butyl-4-{4-[3-(4-methyl-5-cyclopropyl-4H-[1,2,4]triazol-3-ylsulfanyl)-propyl]-piperazin-1-yl}-6-cyclobutyl-pyrimidine fumarate

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

0.4 g of 2-tert-Butyl-4-[4-(3-chloro-propyl)-piperazin-1-yl]-6-cyclobutyl-pyrimidine (1.14 mmol), 0.2 g of 4-methyl-5-cyclopropyl-4H-[1,2,4]triazole-3-thiol (1.29 mmol), 0.07 g lithium-hydroxide (2.92 mmol) and a spatula tip of potassium iodide were stirred in 20 ml of dimethylformamide overnight at room temperature and for an additional 3 h at 40° C. After addition of water and ethyl acetate, the organic layer was separated, dried over magnesium sulfate, filtered and the solvent was evaporated. The residue was purified by column chromatography on silica gel using dichloromethane-methanol (0-2%). Fractions containing the product were combined and the solvents were evaporated. The residue was dissolved in isopropanol and 1 equivalent of fumaric acid was added. The solvent was evaporated and the residue was dissolved in diisopropylether to which some drops of isopropanol were added upon warming, thereby forming a precipitate. After cooling the precipitate was collected by filtration and dried. Yield: 0.04 g (6%)

Workup

  1. customthe organic layer was separated
  2. dry with materialdried over magnesium sulfate
  3. filtrationfiltered
  4. customthe solvent was evaporated
  5. customThe residue was purified by column chromatography on silica gel
  6. additionFractions containing the product
  7. customthe solvents were evaporated
  8. dissolutionThe residue was dissolved in isopropanol
  9. customThe solvent was evaporated
  10. dissolutionthe residue was dissolved in diisopropylether to which some drops of isopropanol
  11. additionwere added
  12. temperatureupon warming
  13. customforming a precipitate
  14. temperatureAfter cooling the precipitate
  15. filtrationwas collected by filtration
  16. customdried

Sources & evidence

ORD record
ord-99ea568edda44dc38cb542cd6d6b8af5
Source dataset
uspto-grants-2012_06
Patent number
US08202868B2

Reaction notes

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