2-Fluoro-5-methylphenyl isocyanate → 1-[4-(3-Chloro-4-cyanoisothiazol-5-yl)phenyl]-3-(2-fluoro-5-methylphenyl)urea

HRID 871003Notes

Reaction equation

HRID 871003 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:12][N:11]=[C:10]([Cl:13])[C:9]=2[C:14]#[N:15])=[CH:4][CH:3]=1.[F:16][C:17]1[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][C:18]=1[N:24]=[C:25]=[O:26]>C1COCC1>[Cl:13][C:10]1[C:9]([C:14]#[N:15])=[C:8]([C:5]2[CH:4]=[CH:3][C:2]([NH:1][C:25]([NH:24][C:18]3[CH:19]=[C:20]([CH3:23])[CH:21]=[CH:22][C:17]=3[F:16])=[O:26])=[CH:7][CH:6]=2)[S:12][N:11]=1

Participants

4

Reactant 2

HCID 27333772-Fluoro-5-methylphenyl isocyanate2×HCID 866892235-(4-Aminophenyl)-3-chloroisothiazole-4-carbonitrile

Product 1

HCID 866892241-[4-(3-Chloro-4-cyanoisothiazol-5-yl)phenyl]-3-(2-fluoro-5-methylphenyl)ureaYield 90.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 5-(4-Aminophenyl)-3-chloroisothiazole-4-carbonitrile (4.565 g, 19.4 mmol) and 2-fluoro-5-methylphenyl isocyanate (5.85 g, 38.7 mmol) in 100 mL of dry THF was heated to reflux overnight. TLC indicated presence of considerable amount of starting material. Additional 2 g of 2-fluoro-5-methylphenyl isocyanate was added and the reaction was continued for another 24 h. The reaction was cooled to RT. THF was removed in vacuo and the resulting solid was stirred in 200 mL of Et2O for 1 h. Product was collected by filtration and washed with Et2O/hexanes to afford a light yellow solid (6.78 g, 90%).

Workup

  1. temperatureto reflux overnight
  2. customTHF was removed in vacuo
  3. filtrationProduct was collected by filtration
  4. washwashed with Et2O/hexanes

Sources & evidence

ORD record
ord-2aaff343e1904d1aa8c5501c749b9629
Source dataset
uspto-grants-2015_03
Patent number
US08969583B2

Reaction notes

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