Acrylamide → HCID 78427113, compound

HRID 631778Notes

Reaction equation

[C:1]([NH2:5])(=[O:4])[CH:2]=[CH2:3].[F:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]([F:16])([F:15])[F:14])=[CH:9][C:8]=1[NH:17][C:18]([NH:20][C:21]1[CH:26]=[CH:25][CH:24]=[C:23](I)[CH:22]=1)=[O:19]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]([F:16])([F:15])[F:14])=[CH:9][C:8]=1[NH:17][C:18]([NH:20][C:21]1[CH:22]=[C:23](/[CH:3]=[CH:2]/[C:1]([NH2:5])=[O:4])[CH:24]=[CH:25][CH:26]=1)=[O:19]

Participants

Conditions

Temperature: 85 °C

Procedure

A mixture of acrylamide (24.7 mg, 0.347 mmol), 1-[2-fluoro-5-(trifluoromethyl)phenyl]-3-(3-iodophenyl)urea (36.8 mg, 0.087 mmol), and palladium(II) acetate (7.8 mg, 0.035 mmol) in 0.8 mL degassed DMF:triethylamine (1:1) was reacted at 75° C. After 14.5 hours a catalytic amount of palladium(II) acetate was added, the temperature increased to 85° C., and the reaction continued for an additional 3.5 hours. The reaction was partitioned between EtOAc and H2O/brine mixture. The EtOAc layer was washed with dilute aqueous HCl, then aqueous NaHCO3, brine, dried with anhydrous Na2SO4 and evaporated. The resulting solid was triturated with CHCl3/MeOH to give the title compound as a light tan solid (8.2 mg, 26%). 1H NMR (Acetone-d6) δ: 8.73-8.82 (m, 2H), 8.41 (br. s., 1H), 7.94 (s, 1H), 7.53 (d, J=15.7 Hz, 1H), 7.30-7.48 (m, 4H), 7.21-7.27 (m, 1H), 7.10 (br. s., 1H), 6.70 (d, J=15.7 Hz, 1H), 6.41 (br. s., 1H).

Workup

customdegassed DMF:triethylamine (1:1)
customwas reacted at 75° C
customThe reaction was partitioned between EtOAc and H2O/brine mixture
washThe EtOAc layer was washed with dilute aqueous HCl
dry with materialaqueous NaHCO3, brine, dried with anhydrous Na2SO4
customevaporated
customThe resulting solid was triturated with CHCl3/MeOH

Sources & evidence

ORD record: ord-f31cdedd1dae48989206638ffdc509b7
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09321721B2

Reaction notes

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