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

HRID 219744Notes

Reaction equation

HRID 219744 reaction equation
[S:1]1[CH:5]=[N:4][N:3]=[C:2]1[SH:6].[OH-].[Li+].[I-].[Na+].[C:11]([C:15]1[N:20]=[C:19]([N:21]2[CH2:26][CH2:25][N:24]([CH2:27][CH2:28][CH2:29]Cl)[CH2:23][CH2:22]2)[CH:18]=[C:17]([CH:31]2[CH2:33][CH2:32]2)[N:16]=1)([CH3:14])([CH3:13])[CH3:12]>CN(C)C=O>[C:11]([C:15]1[N:16]=[C:17]([CH:31]2[CH2:32][CH2:33]2)[CH:18]=[C:19]([N:21]2[CH2:26][CH2:25][N:24]([CH2:27][CH2:28][CH2:29][S:6][C:2]3[S:1][CH:5]=[N:4][N:3]=3)[CH2:23][CH2:22]2)[N:20]=1)([CH3:14])([CH3:12])[CH3:13]

Participants

6

Reactant 4

HCID 3939Lithium HydroxideHCID 5238Sodium IodideHCID 690261252-tert-Butyl-4-[4-(3-chloro-propyl)-piperazin-1-yl]-6-cyclopropyl-pyrimidineHCID 178527973HCID 178527973, compound

Product 1

HCID 115535192-tert-Butyl-4-cyclopropyl-6-{4-[3-([1,3,4]thiadiazol-2-ylsulfanyl)-propyl]-piperazin-1-yl}-pyrimidineYield 52.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
70 °C

Procedure

0.21 g of [1,3,4]thiadiazol-2-thiol (1.77 mmol) were dissolved in 20 ml of dimethylformamide. After addition of 0.04 g of lithium hydroxide (1.77 mmol) and 0.13 g of sodium iodide (0.88 mmol), the reaction mixture was stirred at 70° C. and 0.6 g of 2-tert-butyl-4-[4-(3-chloro-propyl)-piperazin-1-yl]-6-cyclopropyl-pyrimidine (1.77 mmol), dissolved in 5 ml of dimethylformamide, were added dropwise within 2 h. The mixture was stirred at 80° C. for 2 h, cooled to room temperature and the solvent was evaporated. The residue was partitioned between 40 ml of ethyl acetate and 15 ml of saturated aqueous sodium chloride solution. The aqueous phase was reextracted twice with ethyl acetate, the combined organic layers were dried over magnesium sulfate, filtered, and concentrated to dryness, to yield 0.69 g of the crude product, which was further purified by chromatography on silica gel using dichloromethane-methanol (1:1) and ethyl acetate. Fractions containing the product were combined and the solvents were evaporated. The oily residue crystallized upon standing to yield 0.39 g of the title compound.

Workup

  1. additionwere added dropwise within 2 h
  2. stirringThe mixture was stirred at 80° C. for 2 h
  3. temperaturecooled to room temperature
  4. customthe solvent was evaporated
  5. customThe residue was partitioned between 40 ml of ethyl acetate and 15 ml of saturated aqueous sodium chloride solution
  6. dry with materialthe combined organic layers were dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated to dryness
  9. customto yield 0.69 g of the crude product, which
  10. customwas further purified by chromatography on silica gel
  11. additionFractions containing the product
  12. customthe solvents were evaporated
  13. customThe oily residue crystallized

Sources & evidence

ORD record
ord-88a6fcd67aad4b44ae423fa4da73afbb
Source dataset
uspto-grants-2012_06
Patent number
US08202868B2

Reaction notes

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