Reaction equation
[F:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([OH:10])[CH:3]=1.[CH3:11][N:12]([CH3:16])[C:13](Cl)=[O:14].C(N(CC)CC)C>ClC(Cl)C>[C:6]([C:5]1[CH:8]=[CH:9][C:2]([F:1])=[CH:3][C:4]=1[O:10][C:13](=[O:14])[N:12]([CH3:16])[CH3:11])#[N:7]Participants
Procedure
Under N2, a stirred solution of intermediate 129, 4-fluoro-2-hydroxybenzonitrile (685 mg, 5.00 mmol), dimethylcarbamoyl chloride, and triethylamine (606 mg, 6 mmol) in dichloroethane (10 mL) was heated at reflux for 20 hrs. The cooled mixture was diluted with dichloroethane (10 mL) washed with water, and brine. The organic layer was separated, dried (Na2SO4), concentrated, and the residue purified by column chromatography (SiO2, 5% ethyl acetate-CH2Cl2) to provide 700 mg (Yield 67%) of the title compound as a white crystalline solid: 1H NMR (CDCl3, 500 MHz) δ ppm: 3.03 (3H, s, NMe), 3.15 (3H, s, NMe), 6.99 (1H, dt, J=2.5 Hz, 8.5 Hz, Ar—H), 7.23 (1H, dd, J=2.5 Hz, 9.5 Hz, Ar—H), 7.61 (1H, dd, J=9 Hz, 6 Hz, Ar—H); 13C NMR (CDCl3, 125.77 Hz) δ ppm: 36.76, 37.06, 102.84, 102.86, 111.59, 111.79, 113.24, 113.42, 114.99, 134.36, 134.45, 152.54, 155.06, 155.16, 164.26, 166.31. HRMS (ESI) calcd for C10H10N2O2F (M+H) 209.0726, found 209.0722.
Workup
- temperatureat reflux for 20 hrs
- washwashed with water, and brine
- customThe organic layer was separated
- dry with materialdried (Na2SO4)
- concentrationconcentrated
- customthe residue purified by column chromatography (SiO2, 5% ethyl acetate-CH2Cl2)
Sources & evidence
- ORD record
- ord-e4b497e9d72b4493ad07537b4bb8bdd6
- Source dataset
- uspto-grants-2007_02
- Patent number
- US07176196B2
Linked notes
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