Lithium Hydroxide → 2-tert-Butyl-4-cyclopropyl-6-{4-[3-(pyrimidin-2-ylsulfanyl)-propyl]-piperazin-1-yl}-pyrimidine

HRID 219746Notes

Reaction equation

HRID 219746 reaction equation
[SH:1][C:2]1[N:7]=[CH:6][CH:5]=[CH:4][N:3]=1.[OH-].[Li+].[I-].[Na+].[C:12]([C:16]1[N:21]=[C:20]([N:22]2[CH2:27][CH2:26][N:25]([CH2:28][CH2:29][CH2:30]Cl)[CH2:24][CH2:23]2)[CH:19]=[C:18]([CH:32]2[CH2:34][CH2:33]2)[N:17]=1)([CH3:15])([CH3:14])[CH3:13]>CN(C)C=O>[C:12]([C:16]1[N:17]=[C:18]([CH:32]2[CH2:33][CH2:34]2)[CH:19]=[C:20]([N:22]2[CH2:27][CH2:26][N:25]([CH2:28][CH2:29][CH2:30][S:1][C:2]3[N:7]=[CH:6][CH:5]=[CH:4][N:3]=3)[CH2:24][CH2:23]2)[N:21]=1)([CH3:15])([CH3:13])[CH3:14]

Participants

6

Reactant 4

HCID 3939Lithium HydroxideHCID 5238Sodium IodideHCID 690261252-tert-Butyl-4-[4-(3-chloro-propyl)-piperazin-1-yl]-6-cyclopropyl-pyrimidineHCID 178418793HCID 178418793, compound

Product 1

HCID 115388502-tert-Butyl-4-cyclopropyl-6-{4-[3-(pyrimidin-2-ylsulfanyl)-propyl]-piperazin-1-yl}-pyrimidineYield 113%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

0.4 g of 2-mercapto-pyrimidine (3.57 mmol) were dissolved in 20 ml of dimethylformamide. After addition of 0.09 g of lithium hydroxide (3.57 mmol) and 0.27 g of sodium iodide (1.78 mmol), the reaction mixture was stirred at 60° C. and 1.2 g of 2-tert-butyl-4-[4-(3-chloro-propyl)-piperazin-1-yl]-6-cyclopropyl-pyrimidine (3.56 mmol) were added in portions. The reaction mixture was stirred at 60° C. for 1 h, and, after evaporation of dimethylformamide, the residue was partitioned between 30 ml of ethyl acetate and 15 ml of saturated aqueous sodium chloride solution and 15 ml of water. The aqueous phase was re-extracted twice with ethyl acetate. The combined organic layers were dried over magnesium sulfate, filtered, and concentrated to dryness. The crude product was re-dissolved in 30 ml of ethyl acetate and treated with 4 N hydrochloric acid in dioxane. The precipitated hydrochloride salt was collected by filtration and dried to yield 1.66 g of the title compound.

Workup

  1. stirringThe reaction mixture was stirred at 60° C. for 1 h
  2. customafter evaporation of dimethylformamide
  3. customthe residue was partitioned between 30 ml of ethyl acetate and 15 ml of saturated aqueous sodium chloride solution and 15 ml of water
  4. extractionThe aqueous phase was re-extracted twice with ethyl acetate
  5. dry with materialThe combined organic layers were dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated to dryness
  8. dissolutionThe crude product was re-dissolved in 30 ml of ethyl acetate
  9. additiontreated with 4 N hydrochloric acid in dioxane
  10. filtrationThe precipitated hydrochloride salt was collected by filtration
  11. customdried

Sources & evidence

ORD record
ord-ed001a914bf640f7b991be02ba25af60
Source dataset
uspto-grants-2012_06
Patent number
US08202868B2

Reaction notes

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