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

HRID 475440Notes

Reaction equation

HRID 475440 reaction equation
[CH3:1][NH:2][C:3]([C:5]1[CH:10]=[C:9]([O:11][C:12]2[CH:17]=[CH:16][C:15]([NH2:18])=[C:14]([F:19])[CH:13]=2)[CH:8]=[CH:7][N:6]=1)=[O:4].[Cl:20][C:21]1[CH:26]=[CH:25][C:24]([N:27]=[C:28]=[O:29])=[CH:23][C:22]=1[C:30]([F:33])([F:32])[F:31]>C1(C)C=CC=CC=1>[CH3:1][NH:2][C:3]([C:5]1[CH:10]=[C:9]([O:11][C:12]2[CH:17]=[CH:16][C:15]([NH:18][C:28]([NH:27][C:24]3[CH:25]=[CH:26][C:21]([Cl:20])=[C:22]([C:30]([F:32])([F:31])[F:33])[CH:23]=3)=[O:29])=[C:14]([F:19])[CH:13]=2)[CH:8]=[CH:7][N:6]=1)=[O:4]

Participants

4

Reactant 2

HCID 27332651-Chloro-4-isocyanato-2-(trifluoromethyl) benzeneHCID 468352194-(4-Amino-3-fluorophenoxy)-N-methylpyridine-2-carboxamide

Product 1

HCID 11167602RegorafenibYield 47.1%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a solution of 4-(4-amino-3-fluorophenoxy)pyridine-2-carboxylic acid methylamide (177 mg, 0.68 mmol) in toluene (3 mL) was added 4-chloro-3-(trifluoromethyl)phenyl isocyanate (150 mg, 0.68 mmol). The mixture was stirred at rt for 72 h. The reaction was concentrated under reduced pressure and the residue was triturated with diethylether. The resulting solid was collected by filtration and dried in vacuo for 4 h to afford the title compound (155 mg, 0.32 mmol; 47% yield); 1H-NMR (DMSO-d6) 2.78 (d, J=4.9, 3H), 7.03-7.08 (m, 1H), 7.16 (dd, J=2.6, 5.6, 1H), 7.32 (dd, J=2.7, 11.6, 1H), 7.39 (d, J=2.5, 1H), 7.60 (s, 2H), 8.07-8.18 (m, 2H), 8.50 (d, J=5.7, 1H), 8.72 (s, 1H), 8.74-8.80 (m, 1H), 9.50 (s, 1H); MS (HPLC/ES) 483.06 m/z=(M+1).

Workup

  1. concentrationThe reaction was concentrated under reduced pressure
  2. customthe residue was triturated with diethylether
  3. filtrationThe resulting solid was collected by filtration
  4. customdried in vacuo for 4 h

Sources & evidence

ORD record
ord-a0df1dc4c8a148b386b384380c4fcb5a
Source dataset
uspto-grants-2014_01
Patent number
US08637553B2

Reaction notes

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