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

HRID 1918208Notes

Reaction equation

HRID 1918208 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]>ClCCl>[CH3:15][NH:16][C:17]([C:19]1[CH:24]=[C:23]([O:25][C:26]2[CH:27]=[CH:28][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:31][CH:32]=2)[CH:22]=[CH:21][N:20]=1)=[O:18]

Participants

4

Reactant 2

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

Product 1

HCID 216239SorafenibYield 52.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 4-chloro-3-(trifluoromethyl)phenyl isocyanate (101.1 g) in dichloromethane (250 mL) was added to a reaction mixture containing 4-(2-(N-methylcarbamoyl)-4-pyridyloxy)aniline (110.0 g) in dichloromethane (250 mL) at about 0° C. in about 30 minutes. The reaction mixture was stirred at room temperature for about 16 hours. The resulting solid was filtered, washed with dichloromethane (2×200 mL) and dried under reduced pressure at about 35° C. for about 4 hours to obtain sorafenib free base.

Workup

  1. filtrationThe resulting solid was filtered
  2. washwashed with dichloromethane (2×200 mL)
  3. customdried under reduced pressure at about 35° C. for about 4 hours

Sources & evidence

ORD record
ord-a59db6f879ba4458a6bf5696304e8eb9
Source dataset
uspto-grants-2013_12
Patent number
US08618305B2

Reaction notes

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