Dimethylformamide → HCID 16040104, compound

HRID 252064Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([Cl:11])[CH:10]=1)[C:7](=[O:12])[N:6]([CH2:13][CH:14]1[CH2:19][CH2:18][C:17]([F:21])([F:20])[CH2:16][CH2:15]1)[CH2:5]2.[CH3:22][N:23](C=O)C>[C-]#N.[C-]#N.[Zn+2].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:11][C:9]1[CH:10]=[C:2]([C:22]#[N:23])[CH:3]=[C:4]2[C:8]=1[C:7](=[O:12])[N:6]([CH2:13][CH:14]1[CH2:19][CH2:18][C:17]([F:21])([F:20])[CH2:16][CH2:15]1)[CH2:5]2

Participants

Conditions

Temperature: 80 °C

Procedure

5-bromo-7-chloro-2-[(4,4-difluorocyclohexyl)methyl]isoindolin-1-one (1.14 g, 3.01 mmol) was set stirring in DMF (10 mL) under argon and Zn(CN)2 (389 mg, 3.31 mmol) and Pd(PPh3)4 (347 mg, 0.3 mmol) were added. The reaction was stirred at 80° C. for 1.5 hours. The reaction was partitioned between ethyl acetate and water and the organic layer was washed with brine and dried over anhydrous Na2SO4. The solvent was removed under reduced pressure and the product was purified by column chromatography (40% EtOAc/Hexanes) to afford the title compound as a yellow foam (60 mg, 80%). 1H NMR (300 MHz, CDCl3): 7.72 (s, 1H), 7.65 (s, 1H), 4.45 (s, 2H), 3.53 (d, 2H), 2.11-2.15 (m, 2H), 1.66-1.91 (m, 5H), 1.41-1.50 (m, 2H)

Workup

customThe reaction was partitioned between ethyl acetate and water
washthe organic layer was washed with brine
dry with materialdried over anhydrous Na2SO4
customThe solvent was removed under reduced pressure
customthe product was purified by column chromatography (40% EtOAc/Hexanes)

Sources & evidence

ORD record: ord-7ac2d59d36014a5d9641403aee28c7a9
Source dataset: uspto-grants-2011_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07868008B2

Reaction notes

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