Pyridine → N-1,2-Benzisoxazol-3-yl-1-(3-phenyl-1,2,4-thiadiazol-5-yl)piperidine-4-carboxamide

HRID 2262903Notes

Reaction equation

HRID 2262903 reaction equation
[C:1]1([C:7]2[N:11]=[C:10]([N:12]3[CH2:17][CH2:16][CH:15]([C:18]([OH:20])=O)[CH2:14][CH2:13]3)[S:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(Cl)(=O)C(Cl)=O.[O:27]1[C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][C:30]=2[C:29]([NH2:36])=[N:28]1.N1C=CC=CC=1>O1CCCC1.O.CN(C)C=O>[O:27]1[C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][C:30]=2[C:29]([NH:36][C:18]([CH:15]2[CH2:14][CH2:13][N:12]([C:10]3[S:9][N:8]=[C:7]([C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)[N:11]=3)[CH2:17][CH2:16]2)=[O:20])=[N:28]1

Participants

8

Reactant 4

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 27797491,2-Benzoxazol-3-amineHCID 687762351-(3-Phenyl-1,2,4-thiadiazol-5-yl)piperidine-4-carboxylic acid

Product 1

HCID 59594512N-1,2-Benzisoxazol-3-yl-1-(3-phenyl-1,2,4-thiadiazol-5-yl)piperidine-4-carboxamide

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-(3-phenyl-1,2,4-thiadiazol-5-yl)piperidine-4-carboxylic acid (289 mg, 1.00 mmol) and N,N-dimethylformamide (0.010 ml) in tetrahydrofuran (5 ml) was added in water-bath, oxalyl chloride (0.174 ml, 2.00 mmol), and the mixture was stirred at room temperature for 1 hour. The solvent was distilled off under reduced pressure. The residue was added to a solution of 1,2-benzisoxazol-3-amine (134 mg, 1.00 mmol) in pyridine (0.404 ml, 5.00 mmol) under ice-cooling, followed by stirring at room temperature for 1 hour. The solvent was distilled off under reduced pressure. The residue was poured to water and 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 silica gel column chromatography (hexane:ethyl acetate=1:1) to give the desired product as a solid. The resulting solid was recrystallized from a mixed solvent of hexane and ethyl acetate to give 60.3 mg (14.9%) of the desired product.

Workup

  1. distillationThe solvent was distilled off under reduced pressure
  2. temperaturecooling
  3. distillationThe solvent was distilled off under reduced pressure
  4. additionThe residue was poured to water
  5. extractionextracted with ethyl acetate
  6. washThe extract was washed with water
  7. dry with materialdried over anhydrous magnesium sulfate
  8. distillationthe solvent was distilled off under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:1)

Sources & evidence

ORD record
ord-cd375c5432ae4753aa0620113a4a02cc
Source dataset
uspto-grants-2010_12
Patent number
US07851473B2

Reaction notes

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