Water → 2-tert-Butyl-4-[4-(3-chloro-propyl)-piperazin-1-yl]-6-cyclopropyl-pyrimidine

HRID 219696Notes

Reaction equation

HRID 219696 reaction equation
[C:1]([C:5]1[N:10]=[C:9]([N:11]2[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]2)[CH:8]=[C:7]([CH:17]2[CH2:19][CH2:18]2)[N:6]=1)([CH3:4])([CH3:3])[CH3:2].Br[CH2:21][CH2:22][CH2:23][Cl:24].[OH-].[Na+].O>C1(C)C=CC=CC=1.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC>[C:1]([C:5]1[N:10]=[C:9]([N:11]2[CH2:12][CH2:13][N:14]([CH2:21][CH2:22][CH2:23][Cl:24])[CH2:15][CH2:16]2)[CH:8]=[C:7]([CH:17]2[CH2:19][CH2:18]2)[N:6]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 962WaterHCID 80061-Bromo-3-chloropropane2×HCID 14798Sodium HydroxideHCID 673726112-Tert-butyl-4-piperazin-1-yl-6-cyclopropyl-pyrimidine

Product 1

HCID 690261252-tert-Butyl-4-[4-(3-chloro-propyl)-piperazin-1-yl]-6-cyclopropyl-pyrimidineYield 62%

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 1140TolueneSolvent

Procedure

19.2 g of 2-tert-butyl-4-piperazin-1-yl-6-cyclopropyl-pyrimidine (73.7 mmol) were dissolved in 50 ml of toluene. 14.6 ml of 1-bromo-3-chloropropane (147.4 mmol) and 3.4 g of sodium hydroxide (84.7 mmol) were added, followed by dropwise addition of 0.95 g of tetrabutylammonium bromide (2.95 mmol, dissolved in water). After stirring for 5 h at 60° C. additional 1-bromo-3-chloropropane was added to drive the reaction to completion. The reaction mixture was cooled, water was added and the product extracted 3 times with ethyl acetate. The organic layers were dried over magnesium sulfate, filtered, and the solvent was evaporated. The crude product was purified by chromatography on silica gel using dichloromethane/ethyl acetate (9:1). Fractions containing the product were combined, the solvent was evaporated to yield 15.4 g of the title compound.

Workup

  1. additionwas added
  2. customthe reaction to completion
  3. temperatureThe reaction mixture was cooled
  4. extractionthe product extracted 3 times with ethyl acetate
  5. dry with materialThe organic layers were dried over magnesium sulfate
  6. filtrationfiltered
  7. customthe solvent was evaporated
  8. customThe crude product was purified by chromatography on silica gel
  9. additionFractions containing the product
  10. customthe solvent was evaporated

Sources & evidence

ORD record
ord-9b9faa73d69d4006bd6f0d014bbfec6a
Source dataset
uspto-grants-2012_06
Patent number
US08202868B2

Reaction notes

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