4-Methylphenyl isocyanate → 3-[4-({[(4-Methylphenyl)amino]carbonyl}amino)phenyl]-5-{[(2-oxopyrrolidin-1-yl)carbonyl]amino}isothiazole-4-carboxamide

HRID 871009Notes

Reaction equation

HRID 871009 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]([C:13]([NH2:15])=[O:14])=[C:11]([NH:16][C:17]([N:19]3[CH2:23][CH2:22][CH2:21][C:20]3=[O:24])=[O:18])[S:10][N:9]=2)=[CH:4][CH:3]=1.C(N(C(C)C)CC)(C)C.[C:34]1([CH3:43])[CH:39]=[CH:38][C:37]([N:40]=[C:41]=[O:42])=[CH:36][CH:35]=1>CN(C)C=O.CCOC(C)=O>[CH3:43][C:34]1[CH:39]=[CH:38][C:37]([NH:40][C:41]([NH:1][C:2]2[CH:3]=[CH:4][C:5]([C:8]3[C:12]([C:13]([NH2:15])=[O:14])=[C:11]([NH:16][C:17]([N:19]4[CH2:23][CH2:22][CH2:21][C:20]4=[O:24])=[O:18])[S:10][N:9]=3)=[CH:6][CH:7]=2)=[O:42])=[CH:36][CH:35]=1

Participants

6

Reactant 3

HCID 693254-Methylphenyl isocyanateHCID 81531DiisopropylethylamineHCID 716216283-(4-Aminophenyl)-5-{[(2-oxopyrrolidin-1-yl)carbonyl]amino}isothiazole-4-carboxamide

Product 1

HCID 716216293-[4-({[(4-Methylphenyl)amino]carbonyl}amino)phenyl]-5-{[(2-oxopyrrolidin-1-yl)carbonyl]amino}isothiazole-4-carboxamideYield 91.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 3-(4-aminophenyl)-5-{[(2-oxopyrrolidin-1-yl)carbonyl]amino}isothiazole-4-carboxamide (9.6 g, 0.027 mol), diisopropylethylamine (5.3 g, 0.046 mol) in dimethylformamide (150 mL) at ambient temperature was treated with para-Tolyl isocyanate (4.0 g 0.03 mol) over 20 minute period. The resulting mixture was stirred at ambient temperature for 2 hr. The reaction mixture was concentrated in vacuo to give an off white solid, which was stirred in EtOAc (150 mL), filtered the solid and washed with EtOAc to give the title compound as a white solid (11.8 g, 88%).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customto give an off white solid, which
  3. filtrationfiltered the solid
  4. washwashed with EtOAc

Sources & evidence

ORD record
ord-23fabe61206a439991d8ed5c0f28c8aa
Source dataset
uspto-grants-2015_03
Patent number
US08969583B2

Reaction notes

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