Lithium Hydroxide → 2-tert-Butyl-4-cyclobutyl-6-{4-[3-(1-methyl-1H-tetrazol-5-ylsulfanyl)-propyl]-piperazin-1-yl}-pyrimidine

HRID 219722Notes

Reaction equation

HRID 219722 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]([SH:31])=[N:29][N:28]=[N:27]1.[OH-].[Li+].[I-].[K+]>CN(C)C=O>[C:1]([C:5]1[N:6]=[C:7]([CH:21]2[CH2:24][CH2:23][CH2:22]2)[CH:8]=[C:9]([N:11]2[CH2:16][CH2:15][N:14]([CH2:17][CH2:18][CH2:19][S:31][C:30]3[N:26]([CH3:25])[N:27]=[N:28][N:29]=3)[CH2:13][CH2:12]2)[N:10]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 3939Lithium HydroxideHCID 4875Potassium IodideHCID 666731042-tert-Butyl-4-[4-(3-chloro-propyl)-piperazin-1-yl]-6-cyclobutyl-pyrimidineHCID 178482017HCID 178482017, compound

Product 1

HCID 115464802-tert-Butyl-4-cyclobutyl-6-{4-[3-(1-methyl-1H-tetrazol-5-ylsulfanyl)-propyl]-piperazin-1-yl}-pyrimidineYield 49.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

0.5 g of 2-tert-Butyl-4-[4-(3-chloro-propyl)-piperazin-1-yl]-6-cyclobutyl-pyrimidine (1.42 mmol) were dissolved in 15 ml of dimethylformamide. 0.18 g of 1-methyl-1H-tetrazole-5-thiol (1.56 mmol), 0.09 g of lithium hydroxide (3.76 mmol) and a spatula tip of potassium iodide were added. The mixture was stirred for 2 h at 60° C. After cooling to room temperature, the reaction mixture was partitioned between water and ethyl acetate. The ethyl acetate layer was dried over magnesium sulfate, filtered, and the solvent evaporated under vacuum. The resulting crude product was purified by column chromatography on silica gel using dichloromethane-methanol (1-5%). Fractions containing the product were combined and the solvent was evaporated under vacuum. The residue was treated with acetonitril, the solvent evaporated, whereby 0.3 g of the title compound were obtained as an oily residue.

Workup

  1. temperatureAfter cooling to room temperature
  2. customthe reaction mixture was partitioned between water and ethyl acetate
  3. dry with materialThe ethyl acetate layer was dried over magnesium sulfate
  4. filtrationfiltered
  5. customthe solvent evaporated under vacuum
  6. customThe resulting crude product was purified by column chromatography on silica gel
  7. additionFractions containing the product
  8. customthe solvent was evaporated under vacuum
  9. additionThe residue was treated with acetonitril
  10. customthe solvent evaporated

Sources & evidence

ORD record
ord-c935e735fe454d0dae5b581e5f5ab9bc
Source dataset
uspto-grants-2012_06
Patent number
US08202868B2

Reaction notes

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