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

HRID 219745Notes

Reaction equation

HRID 219745 reaction equation
[CH3:1][C:2]1[S:6][C:5]([SH:7])=[N: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:7][C:5]3[S:6][C:2]([CH3:1])=[N:3][N:4]=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 178434161HCID 178434161, compound

Product 1

HCID 116549402-tert-Butyl-4-cyclopropyl-6-{4-[3-(5-methyl-[1,3,4]thiadiazol-2-ylsulfanyl)-propyl]-piperazin-1-yl}-pyrimidineYield 90.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
70 °C

Procedure

0.23 g of 5-methyl-[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, added dropwise over 2 h. The mixture was stirred at 80° C. for 2 h. The dimethylformamide was then evaporated. The residue was partitioned between 40 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, to yield 0.69 g of the title compound as an oily residue. 0.8 g of the crude product were treated with 10 ml of n-hexane, the precipitate was collected by filtration and dried to yield 0.56 g of the title compound.

Workup

  1. additionadded dropwise over 2 h
  2. stirringThe mixture was stirred at 80° C. for 2 h
  3. customThe dimethylformamide was then evaporated
  4. customThe residue was partitioned between 40 ml of ethyl acetate and 15 ml of saturated aqueous sodium chloride solution and 15 ml of water
  5. extractionThe aqueous phase was re-extracted twice with ethyl acetate
  6. dry with materialThe combined organic layers were dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-e346f71d833f43989e60d4644942779e
Source dataset
uspto-grants-2012_06
Patent number
US08202868B2

Reaction notes

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