Methyl Isocyanate → 1-Methyl-3-(4-cyano-3-(dimethylamino)-5-isothiazolyl)urea

HRID 616494Notes

Reaction equation

HRID 616494 reaction equation
[NH2:1][C:2]1[S:6][N:5]=[C:4]([N:7]([CH3:9])[CH3:8])[C:3]=1[C:10]#[N:11].[CH3:12][N:13]=[C:14]=[O:15].C([O-])(=O)C.C([O-])(=O)C.C([Sn+2]CCCC)CCC>C([O-])(=O)C.C([O-])(=O)C.C([Sn+2]CCCC)CCC.O1CCCC1>[CH3:12][NH:13][C:14]([NH:1][C:2]1[S:6][N:5]=[C:4]([N:7]([CH3:8])[CH3:9])[C:3]=1[C:10]#[N:11])=[O:15]

Participants

6

Reactant 3

HCID 12228Methyl Isocyanate3×HCID 9798523Di-n-butyl diacetoxy tinHCID 203675775-Amino-4-cyano-3-(dimethylamino)isothiazole

Product 1

HCID 203675871-Methyl-3-(4-cyano-3-(dimethylamino)-5-isothiazolyl)urea

Reagents, catalysts & solvents 2

HCID 9798523Di-n-butyl diacetoxy tinCatalyst2×HCID 8028TetrahydrofuranSolvent2×

Procedure

Ten drops of dibutyltin diacetate were added to a solution of 3.0 g of 5-amino-4-cyano-3-(dimethylamino)-isothiazole and 1.9 g of methyl isocyanate in 25 ml of tetrahydrofuran. The solution was heated under reflux for two hours, at which time thin-layer chromatographic analysis indicated the reaction to be 40% complete. After the addition of 5 ml more of dibutyltin diacetate and 2 ml more of methyl isocyanate, heating was continued for 90 minutes. Thin-layer chromatographic analysis indicated the reaction to be 60% complete. An additional 15 ml of tetrahydrofuran to dissolve the precipitate which had formed, 10 drops of dibutyltin diacetate, and 3 ml of methyl isocyanate were added and heating was continued for three hours. Thin-layer chromatographic analysis indicated approximately 90% conversion to the desired product. The reaction mixture was stirred at ambient temperature overnight, 2 ml more of methyl isocyanate were added, and the solution was heated under reflux for 1 hour. Thin-layer chromatographic analysis indicated 95% completion. The reaction mixture was cooled to -10°, the solid was collected by filtration and washed with water. Purification was accomplished by recrystallization from 300 ml of methanol to give a solid, m.p. 240°-241°. A second crop of solid, m.p. 240°-241°, was also collected to give a total yield of 6.2 g of 1-methyl-3-(4-cyano-3-(dimethylamino)-5-isothiazolyl)urea. The nmr spectrum was consistent with the assigned structure.

Workup

  1. temperatureThe solution was heated
  2. temperatureunder reflux for two hours, at which time thin-layer chromatographic analysis
  3. customthe reaction
  4. temperatureheating
  5. customthe reaction
  6. customhad formed
  7. temperatureheating
  8. waitwas continued for three hours

Sources & evidence

ORD record
ord-51079813b92f42619f0ef9bc82dd0cdc
Source dataset
uspto-grants-1978_02
Patent number
US04075001

Reaction notes

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