3-Bromo-4-fluorophenylacetylene

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Using essentially the same procedure described in Example 1, steps a-c, and employing 3-bromo-4-fluoro-1-ethynylbenzene the racemic mixture of 2-amino-5-(3-bromo-4-fluorophenyl)-5-[4-(difluoromethoxy)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one was obtained and separated by chiral chromatography technique (Chiralcel OJ, 0.46×10 cm, using 15% ethanol in 85% hexane and diethylamine as the mobile phase) to give the title enantiomer, MS m/e (M+H)+ 332; 1H NMR (400 MHz, DMSO-d6) 2.94 (s, 3H), 6.74 (brs, 2H), 7.1 (d, J=8.75 Hz, 2H), 7.13-7.65 (m, 5H), 7.67 (d, J=2.2 Hz, 1H); [a]25=−22 (C=1% in MeOH). was obtained separated by chiral chromatography technique (Chiralcel OJ, 0.46×10 cm to give the title enantiomer, MS m/e (M+H)+ 332

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 1-ethyl-4-iodo-2-methanesulfonyl-1H-pyrrole (0.28 g, 0.94 mmol) in DMF was treated with dichlorobis(triphenylphosphine)-palladium(II) (0.033 g, 0.05 mmol), triphenylphosphine (0.0054 g, 0.028 mmol) and triethylamine (0.68 mL, 4.9 mmol), treated dropwise with a solution of 2-bromo-4-ethynyl-1-fluorobenzene (0.28 g, 1.4 mmol) in DMF, stirred at room temperature for 18 h, poured into EtOAc and washed sequentially with water and brine. The organic phase is separated, dried (Na2SO4) and concentrated in vacuo. Chromatography of the resultant residue (silica gel, 2%-20% EtOAC-hexanes as eluent) yielded an oil; 1H NMR (400 MHz, CDCl3) δ: 1.50 (t, 3H, J=7.3 Hz), 3.12 (s, 3H), 4.28 (q, 2H, J=7.3 Hz), 7.01 (d, 1H, J=1.8 Hz), 7.07 (t, 1H, J=8.5 Hz), 7.12 (d, 1H, J=1.8 Hz), 7.37 (m, 1H), 7.66 (dd, 1H, J=2.1, 6.6 Hz). washed sequentially with water and brine The organic phase is separated dried (Na2SO4) concentrated in vacuo

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Using essentially the same procedure described in Example 1, steps a-c, and employing 3-bromo-4-fluoro-1-ethynylbenzene the racemic mixture of 2-amino-5-(3-bromo-4-fluorophenyl)-5-[4-(difluoromethoxy)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one was obtained and separated by chiral chromatography technique (Chiralcel OJ, 0.46×10 cm, using 15% ethanol in 85% hexane and diethylamine as the mobile phase) to give the title enantiomer, MS m/e (M+H)+ 332; 1H NMR (400 MHz, DMSO-d6) 2.94 (s, 3H), 6.74 (brs, 2H), 7.1 (d, J=8.75 Hz, 2H), 7.13-7.65 (m, 5H), 7.67 (d, J=2.2 Hz, 1H); [a]25=−22 (C=1% in MeOH). was obtained separated by chiral chromatography technique (Chiralcel OJ, 0.46×10 cm to give the title enantiomer, MS m/e (M+H)+ 332

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Using essentially the same procedure described in Example 1, steps a-c, and employing 3-bromo-4-fluoro-1-ethynylbenzene the racemic mixture of 2-amino-5-(3-bromo-4-fluorophenyl)-5-[4-(difluoromethoxy)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one was obtained and separated by chiral chromatography technique (Chiralcel OJ, 0.46×10 cm, using 15% ethanol in 85% hexane and diethylamine as the mobile phase) to give the title enantiomer, MS m/e (M+H)+ 332; 1H NMR (400 MHz, DMSO-d6) 2.94 (s, 3H), 6.74 (brs, 2H), 7.1 (d, J=8.75 Hz, 2H), 7.13-7.65 (m, 5H), 7.67 (d, J=2.2 Hz, 1H); [a]25=−22 (C=1% in MeOH). was obtained separated by chiral chromatography technique (Chiralcel OJ, 0.46×10 cm to give the title enantiomer, MS m/e (M+H)+ 332

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 1-ethyl-4-iodo-2-methanesulfonyl-1H-pyrrole (0.28 g, 0.94 mmol) in DMF was treated with dichlorobis(triphenylphosphine)-palladium(II) (0.033 g, 0.05 mmol), triphenylphosphine (0.0054 g, 0.028 mmol) and triethylamine (0.68 mL, 4.9 mmol), treated dropwise with a solution of 2-bromo-4-ethynyl-1-fluorobenzene (0.28 g, 1.4 mmol) in DMF, stirred at room temperature for 18 h, poured into EtOAc and washed sequentially with water and brine. The organic phase is separated, dried (Na2SO4) and concentrated in vacuo. Chromatography of the resultant residue (silica gel, 2%-20% EtOAC-hexanes as eluent) yielded an oil; 1H NMR (400 MHz, CDCl3) δ: 1.50 (t, 3H, J=7.3 Hz), 3.12 (s, 3H), 4.28 (q, 2H, J=7.3 Hz), 7.01 (d, 1H, J=1.8 Hz), 7.07 (t, 1H, J=8.5 Hz), 7.12 (d, 1H, J=1.8 Hz), 7.37 (m, 1H), 7.66 (dd, 1H, J=2.1, 6.6 Hz). washed sequentially with water and brine The organic phase is separated dried (Na2SO4) concentrated in vacuo

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 1-ethyl-4-iodo-2-methanesulfonyl-1H-pyrrole (0.28 g, 0.94 mmol) in DMF was treated with dichlorobis(triphenylphosphine)-palladium(II) (0.033 g, 0.05 mmol), triphenylphosphine (0.0054 g, 0.028 mmol) and triethylamine (0.68 mL, 4.9 mmol), treated dropwise with a solution of 2-bromo-4-ethynyl-1-fluorobenzene (0.28 g, 1.4 mmol) in DMF, stirred at room temperature for 18 h, poured into EtOAc and washed sequentially with water and brine. The organic phase is separated, dried (Na2SO4) and concentrated in vacuo. Chromatography of the resultant residue (silica gel, 2%-20% EtOAC-hexanes as eluent) yielded an oil; 1H NMR (400 MHz, CDCl3) δ: 1.50 (t, 3H, J=7.3 Hz), 3.12 (s, 3H), 4.28 (q, 2H, J=7.3 Hz), 7.01 (d, 1H, J=1.8 Hz), 7.07 (t, 1H, J=8.5 Hz), 7.12 (d, 1H, J=1.8 Hz), 7.37 (m, 1H), 7.66 (dd, 1H, J=2.1, 6.6 Hz). washed sequentially with water and brine The organic phase is separated dried (Na2SO4) concentrated in vacuo