Dimethylformamide → 3-chloro-5-[(5-chloro-1H-indazol-4-yl)oxy]benzonitrile

HRID 505504Notes

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

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

Workup

temperatureAfter this time, the reaction was cooled to room temperature
custompartitioned between saturated aq. NH4Cl (500 mL), water (500 mL) and EtOAc (2×1000 mL)
dry with materialThe combined extracts were dried over MgSO4
customabsorbed onto silica gel (200 g)
customthe solvent removed in vacuo
customThis solid was purified on a silica gel (1000 g) column (0-10% EtOAc/CH2Cl2)

Sources & evidence

ORD record: ord-43a9e2f84f874303ae3a5ec582a6c1ae
Source dataset: uspto-grants-2010_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07781454B2

Reaction notes

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