Lithium Hydroxide → Hydrochloric Acid

HRID 219718Notes

Reaction equation

HRID 219718 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:31])[CH2:24][CH2:23]2)[CH:19]=[C:18]([CH:32]2[CH2:35][CH2:34][CH2:33]2)[N:17]=1)([CH3:15])([CH3:14])[CH3:13]>CN(C)C=O>[ClH:31].[C:12]([C:16]1[N:17]=[C:18]([CH:32]2[CH2:33][CH2:34][CH2:35]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].[ClH:31]

Participants

7

Reactant 4

HCID 3939Lithium HydroxideHCID 5238Sodium IodideHCID 666731042-tert-Butyl-4-[4-(3-chloro-propyl)-piperazin-1-yl]-6-cyclobutyl-pyrimidineHCID 178418793HCID 178418793, compound

Product 2

HCID 313Hydrochloric AcidHCID 690283502-tert-Butyl-4-cyclobutyl-6-{4-[3-(pyrimidin-2-ylsulfanyl)-propyl]-piperazin-1-yl}-pyrimidine hydrochloride

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 1.25 g of 2-tert-butyl-4-[4-(3-chloro-propyl)-piperazin-1-yl]-6-cyclobutyl-pyrimidine (3.57 mmol) were added in portions. The mixture was stirred at 60° C. for 1 h. After cooling, the dimethylformamide was evaporated and the residue was partitioned between 30 ml of ethyl acetate and half-saturated sodium chloride solution (15 ml of saturated aqueous sodium chloride solution and 15 ml of water). The aqueous phase was reextracted twice with ethyl acetate. The combined organic layers were dried over magnesium sulfate, filtered, and concentrated to dryness. The crude product was redissolved in 30 ml of ethyl acetate. The hydrochloride was formed by addition of 4 N hydrochloric acid in dioxane to yield 1.8 g of the title compound as a crystallized hydrochloride salt.

Workup

  1. stirringThe mixture was stirred at 60° C. for 1 h
  2. temperatureAfter cooling
  3. customthe dimethylformamide was evaporated
  4. customthe residue was partitioned between 30 ml of ethyl acetate and half-saturated sodium chloride solution (15 ml of saturated aqueous sodium chloride solution and 15 ml of water)
  5. dry with materialThe combined organic layers were dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated to dryness
  8. dissolutionThe crude product was redissolved in 30 ml of ethyl acetate

Sources & evidence

ORD record
ord-ff387543f4a44429bc000989f0b2b8b1
Source dataset
uspto-grants-2012_06
Patent number
US08202868B2

Reaction notes

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