(5-chloro-2,3-dihydro-1-benzofuran-2-yl)-piperazin-1-ylmethanone

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2-[(4-[[4-nitro-3-(trifluoromethyl)phenyl]amino]cyclohexyl)oxy]acetic acid (100 mg, 0.28 mmol) in dichloromethane (20 ml) was added EDAC.HCl (80 mg, 0.42 mmol 1.5 eq), HOBt (56 mg, 0.41 mmol, 1.5 eq), triethylamine (84 mg, 0.83 mmol, 3 eq) and 1-[(5-chloro-2,3-dihydro-1-benzofuran-2-yl)carbonyl]piperazine (74 mg, 0.28 mmol, 1 eq). The resulting solution was stirred overnight at room temperature and then concentrated under vacuum. The crude residue was purified by silica gel chromatography using 5-20% ethyl acetate in dichloromethane to elute. The product-containing fractions were combined and concentrated under vacuum to afford 1-[4-[(5-chloro-2,3-dihydro-1-benzofuran-2-yl)carbonyl]piperazin-1-yl]-2-[(4-[[4-nitro-3-(trifluoromethyl)phenyl]amino]cyclohexyl)oxy]ethan-1-one as a yellow solid (34.9 mg, 19%). (ES, m/z): [M+H]+ 611.25; 1H NMR (300 MHz, CDCl3): δ 8.00 (d, J=9.0 Hz, 1H), 7.18 (s, 1H), 7.07 (d, J=8.4 Hz, 1H), 6.85 (d, J=2.1 Hz, 1H), 6.70 (d, J=8.7 Hz, 1H), 6.63 (dd, J=2.1 Hz, 9.0 Hz, 1H), 5.42 (dd, J=7.5 Hz, 9.0 Hz, 1H), 4.23 (s, 2H), 3.82-3.98 (m, 4H), 3.30-3.70 (m, 8H), 2.10-2.20 (m, 4H), 1.42-1.58 (m, 2H), 1.20-1.40 (m, 2H). concentrated under vacuum The crude residue was purified by silica gel chromatography to elute concentrated under vacuum

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of tert-butyl 4-[(5-chloro-2,3-dihydro-1-benzofuran-2-yl)carbonyl]piperazine-1-carboxylate (400 mg, 1.09 mmol) in dichloromethane (5 ml) was treated with trifluoroacetic acid (1 ml). The resulting solution was stirred for 2 h at room temperature and then concentrated under vacuum to give a residue. The crude material was dissolved into water (20 ml) and the pH was adjusted to ˜8 using aqueous sodium bicarbonate. The mixture was extracted with ethyl acetate (3×100 ml). The organic layers were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum to afford 1-[(5-chloro-2,3-dihydro-1-benzofuran-2-yl)carbonyl]piperazine as light yellow oil (280 mg, 96%). (ES, m/z): [M+H]+ 267; 1H NMR (300 MHz, CDCl3): δ 7.20 (s, 1H), 7.05-7.11 (m, 1H), 6.70 (d, J=8.4 Hz, 1H), 5.46-5.55 (m, 1H), 3.85-3.95 (m, 3H), 3.53-3.63 (m, 2H), 3.25-3.35 (m, 1H), 2.90-3.05 (m, 4H). concentrated under vacuum to give a residue The mixture was extracted with ethyl acetate (3×100 ml) dried over anhydrous sodium sulfate filtered concentrated under vacuum