1-Chloro-4-isocyanato-2-(trifluoromethyl) benzene → Sorafenib

HRID 1512154Notes

Reaction equation

HRID 1512154 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]=[C:9]=[O:10])=[CH:4][C:3]=1[C:11]([F:14])([F:13])[F:12].[CH3:15][NH:16][C:17]([C:19]1[CH:24]=[C:23]([O:25][C:26]2[CH:32]=[CH:31][C:29]([NH2:30])=[CH:28][CH:27]=2)[CH:22]=[CH:21][N:20]=1)=[O:18]>>[CH3:15][NH:16][C:17]([C:19]1[CH:24]=[C:23]([O:25][C:26]2[CH:32]=[CH:31][C:29]([NH:30][C:9]([NH:8][C:5]3[CH:6]=[CH:7][C:2]([Cl:1])=[C:3]([C:11]([F:12])([F:13])[F:14])[CH:4]=3)=[O:10])=[CH:28][CH:27]=2)[CH:22]=[CH:21][N:20]=1)=[O:18]

Participants

3

Reactant 2

HCID 27332651-Chloro-4-isocyanato-2-(trifluoromethyl) benzeneHCID 166551294-(4-Aminophenoxy)-N-methylpicolinamide

Product 1

HCID 216239SorafenibYield 93.2%

Procedure

A solution of 4-chloro-3-(trifluoromethyl)phenylisocyanate (14.60 g, 65.90 mmol) in CH2C12 (35 mL) was added dropwise to a suspension of 4-(2-(N-methylcarbamoyl)-4-pyridyloxy)aniline (MethodA2, Step 4; 16.0 g, 65.77 mmol) in CH2C12 (35 mL) at 0° C. The resulting mixture was stirred at room temp. for 22 h. The resulting yellow solids were removed by filtration, then washed with CH2C12 (2×30 mL) and dried under reduced pressure to afford N-(4-chloro-3-(trifluoromethyl)phenyl)-N′-(4-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl) as an off white solid (28.5 g, 93%)

Workup

  1. customThe resulting yellow solids were removed by filtration
  2. washwashed with CH2C12 (2×30 mL)
  3. customdried under reduced pressure

Sources & evidence

ORD record
ord-51be6fbbecbe435bb7e1e082271ee179
Source dataset
uspto-grants-2012_07
Patent number
US08217061B2

Reaction notes

Loading…