Dimethylformamide → 3-chloro-5-[(5-chloro-1H-indazol-4-yl)oxy]benzonitrile
Reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:16]=[C:17]([Cl:19])[CH:18]=1)[O:5][C:6]1[C:14]([Cl:15])=[CH:13][CH:12]=[C:11]2[C:7]=1[CH:8]=[N:9][NH:10]2.[CH3:20][N:21](C=O)C>[C-]#N.[Zn+2].[C-]#N>[Cl:19][C:17]1[CH:18]=[C:2]([CH:3]=[C:4]([O:5][C:6]2[C:14]([Cl:15])=[CH:13][CH:12]=[C:11]3[C:7]=2[CH:8]=[N:9][NH:10]3)[CH:16]=1)[C:20]#[N:21]Participants
4
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 90 °C
Procedure
To a suspension of 4-(3-bromo-5-chlorophenoxy)-5-chloro-1H-indazole (40 g, 112 mmol) and zinc cyanide (15.74 g, 134 mmol) in DMF (400 mL) was added palladium tetrakis triphenylphosphine (38.7 g, 33.5 mmol) and heated to 90° C. for 1 hour. After this time, the reaction was cooled to room temperature and partitioned between saturated aq. NH4Cl (500 mL), water (500 mL) and EtOAc (2×1000 mL). The combined extracts were dried over MgSO4, absorbed onto silica gel (200 g) and the solvent removed in vacuo. This solid was purified on a silica gel (1000 g) column (0-10% EtOAc/CH2Cl2) to give the title compound as a white solid. LRMS (M+1)=303.9