Water → 4-[4-(4-fluorophenyl)-1,3-thiazol-2-yl]-N-pyridazin-3-ylpiperazine-1-carboxamide

HRID 2263206

Reaction equation

HRID 2263206 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([NH:7][C:8](=[O:15])OCC(Cl)(Cl)Cl)[N:2]=1.[F:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]2[N:24]=[C:25]([N:28]3[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]3)[S:26][CH:27]=2)=[CH:19][CH:18]=1.C(N(C(C)C)CC)(C)C.O>CS(C)=O>[F:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]2[N:24]=[C:25]([N:28]3[CH2:29][CH2:30][N:31]([C:8]([NH:7][C:3]4[N:2]=[N:1][CH:6]=[CH:5][CH:4]=4)=[O:15])[CH2:32][CH2:33]3)[S:26][CH:27]=2)=[CH:19][CH:18]=1

Participants

6

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 80272011-[4-(4-Fluorophenyl)-2-thiazolyl]piperazineHCID 685766982,2,2-Trichloroethyl pyridazin-3-ylcarbamate

Product 1

HCID 687784504-[4-(4-fluorophenyl)-1,3-thiazol-2-yl]-N-pyridazin-3-ylpiperazine-1-carboxamideYield 11.1%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 2,2,2-trichloroethyl pyridazin-3-ylcarbamate (226 mg, 0.835 mmol), 4-[4-(4-fluorophenyl)-1,3-thiazol-2-yl]piperazine (200 mg, 0.760 mmol) and diisopropylethylamine (0.265 ml, 1.52 mmol) in dimethylsulfoxide (2.5 ml) was stirred at 70° C. for 3 days. Water was poured into the reaction solution, and the mixture was extracted with ethyl acetate. The extract was washed with water and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by high performance liquid chromatography (YMC HPLC column; Solution A: 0.1% trifluoroacetic acid solution in acetonitrile; Solution B: 0.1% aqueous trifluoroacetic acid solution; eluted with 10% Solution A to 100% Solution A), and a saturated aqueous sodium hydrogen carbonate solution was added. The mixture was extracted with ethyl acetate. The extract was washed with water and dried over magnesium sulfate anhydrous, and the solvent was distilled off under reduced pressure. The residue was recrystallized from a mixed solvent of hexane and tetrahydrofuran to give the desired product (32.3 mg, 11.1%) as a solid.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe extract was washed with water
  3. dry with materialdried over anhydrous magnesium sulfate
  4. distillationthe solvent was distilled off under reduced pressure
  5. customThe residue was purified by high performance liquid chromatography (YMC HPLC column; Solution A: 0.1% trifluoroacetic acid solution in acetonitrile; Solution B: 0.1% aqueous trifluoroacetic acid solution; eluted with 10% Solution A to 100% Solution A)
  6. additiona saturated aqueous sodium hydrogen carbonate solution was added
  7. extractionThe mixture was extracted with ethyl acetate
  8. washThe extract was washed with water
  9. dry with materialdried over magnesium sulfate anhydrous
  10. distillationthe solvent was distilled off under reduced pressure
  11. customThe residue was recrystallized from a mixed solvent of hexane and tetrahydrofuran

Sources & evidence

ORD record
ord-303f3fef2cad4b8999fccc5fa6713003
Source dataset
uspto-grants-2010_12
Patent number
US07851473B2

Linked notes

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