Lithium Hydroxide → 2-tert-Butyl-4-{4-[3-(4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl)-propyl]-piperazin-1-yl}-6-cyclopropyl-pyrimidine acetate

HRID 219751Notes

Reaction equation

HRID 219751 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[CH2:23][CH2:22]2)[N:6]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:24][N:25]1[CH:29]=[N:28][N:27]=[C:26]1[SH:30].[OH-:31].[Li+].[I-].[Na+].CN(C)C=[O:38]>>[C:23]([OH:38])(=[O:31])[CH3:21].[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:30][C:26]3[N:25]([CH3:24])[CH:29]=[N:28][N:27]=3)[CH2:13][CH2:12]2)[CH:8]=[C:7]([CH:21]2[CH2:23][CH2:22]2)[N:6]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 5

HCID 3939Lithium HydroxideHCID 5238Sodium IodideHCID 6228DimethylformamideHCID 690261252-tert-Butyl-4-[4-(3-chloro-propyl)-piperazin-1-yl]-6-cyclopropyl-pyrimidineHCID 178481306HCID 178481306, compound

Product 1

HCID 690760382-tert-Butyl-4-{4-[3-(4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl)-propyl]-piperazin-1-yl}-6-cyclopropyl-pyrimidine acetate

Conditions

Temperature
70 °C

Procedure

0.7 g of 2-tert-Butyl-4-[4-(3-chloro-propyl)-piperazin-1-yl]-6-cyclopropyl-pyrimidine (1.45 mmol) and 0.55 g of 4-methyl-4H-[1,2,4]triazole-3-thiol (2.08 mmol) were dissolved in 10 ml of dimethylformamide. After addition of 0.104 g of lithium hydroxide (4.36 mmol) and 0.109 g of sodium iodide (0.73 mmol), the reaction mixture was stirred at 70° C. for 3 h. After cooling, the solvent was evaporated and the residue partitioned between dichloromethane and half-saturated sodium chloride solution. The organic layer was dried over magnesium sulfate, filtered, and the solvent was evaporated. The residue was purified via preparative HPLC on a C18-Symmetry column (Waters) with water/methanol (0.1% acetic acid). Fractions containing the product were combined and lyophilised to yield 0.075 g of the product.

Workup

  1. temperatureAfter cooling
  2. customthe solvent was evaporated
  3. customthe residue partitioned between dichloromethane and half-saturated sodium chloride solution
  4. dry with materialThe organic layer was dried over magnesium sulfate
  5. filtrationfiltered
  6. customthe solvent was evaporated
  7. customThe residue was purified via preparative HPLC on a C18-Symmetry column (Waters) with water/methanol (0.1% acetic acid)
  8. additionFractions containing the product

Sources & evidence

ORD record
ord-ab2aa95b5690499ba8b774fa342168e1
Source dataset
uspto-grants-2012_06
Patent number
US08202868B2

Reaction notes

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