Potassium Carbonate → Methyl 4-[({[4-cyano-3-(4-nitrophenyl)isothiazol-5-yl]amino}carbonyl)amino]butanoate

HRID 871006Notes

Reaction equation

HRID 871006 reaction equation
[NH2:1][C:2]1[S:6][N:5]=[C:4]([C:7]2[CH:12]=[CH:11][C:10]([N+:13]([O-:15])=[O:14])=[CH:9][CH:8]=2)[C:3]=1[C:16]#[N:17].C(=O)([O-])[O-].[K+].[K+].[CH3:24][O:25][C:26](=[O:33])[CH2:27][CH2:28][CH2:29][N:30]=[C:31]=[O:32]>O1CCCC1>[C:16]([C:3]1[C:4]([C:7]2[CH:8]=[CH:9][C:10]([N+:13]([O-:15])=[O:14])=[CH:11][CH:12]=2)=[N:5][S:6][C:2]=1[NH:1][C:31]([NH:30][CH2:29][CH2:28][CH2:27][C:26]([O:25][CH3:24])=[O:33])=[O:32])#[N:17]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 2759393Methyl 4-isocyanatobutanoateHCID 690551855-Amino-3-(4-nitrophenyl)isothiazole-4-carbonitrile

Product 1

HCID 86689227Methyl 4-[({[4-cyano-3-(4-nitrophenyl)isothiazol-5-yl]amino}carbonyl)amino]butanoateYield 80.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 5-amino-3-(4-nitrophenyl)isothiazole-4-carbonitrile (25.0 g, 0.101 mol) in tetrahydrofuran (300 mL) dimethylsulfoxide (40 mL) at ambient temperature was treated with potassium carbonate (35.0 g, 0.25 mol). The resulting mixture was stirred at ambient temperature for 15 min. The reaction mixture was treated with 4-isocyanato-butyric acid methyl ester (21.8 g, 0.15 mol) at ambient temperature. The mixture was stirred at ambient temperature overnight. The reaction mixture was filtered through celite and filtrate concentrated in vacuo. The residue was dissolved EtOAc (600 mL) and washed with water and brine then dried (sodium sulfate), filtered, solvent concentrated in vacuo. The crude residue was purified by column chromatography (20% ethyl acetate in dichloromethane) to give the title compound as a light brown solid (31.5 g, 78%).

Workup

  1. stirringThe mixture was stirred at ambient temperature overnight
  2. filtrationThe reaction mixture was filtered through celite and filtrate
  3. concentrationconcentrated in vacuo
  4. dissolutionThe residue was dissolved EtOAc (600 mL)
  5. washwashed with water and brine
  6. dry with materialthen dried (sodium sulfate)
  7. filtrationfiltered
  8. concentrationsolvent concentrated in vacuo
  9. customThe crude residue was purified by column chromatography (20% ethyl acetate in dichloromethane)

Sources & evidence

ORD record
ord-0007843c66bf419a9d98952a8baaede5
Source dataset
uspto-grants-2015_03
Patent number
US08969583B2

Reaction notes

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