4-(chloromethyl)-N-ethylbenzamide

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

実験手順: Cesium carbonate (1.4 mmol) was added to a solution of (1R,2S)-2-(4-Chlorobenzenesulfonylamino)-cyclohexanecarboxylic acid amide (0.62 mmol) in DMF (7 mL). 4-Chloromethyl-N-ethylbenzamide (0.76 mmol) was added to the mixture followed by potassium iodide (0.75 mmol). Reaction was stirred at room temperature overnight. Reaction mixture was diluted with ethyl acetate (20 mL) then was washed with water (2×15 mL). Organic layer was concentrated in vacuo. Residue was purified by preparatory HPLC (acetonitrile/water/trifluoroacetic acid). Proper fractions were combined. Acetonitrile was removed from the mixture in vacuo. Remaining aqueous was frozen and lyophilized to yield 4-[[(1R,2S)-(2-Carbamoyl-cyclohexyl)-(4-chlorobenzenesulfonyl)-amino]-methyl]-N-ethyl benzamide (120 mg) as a white solid in 40% yield.: 1H NMR (300 Mz, DMSO-d6) δ 8.40 (t, 1 H), 7.79 (d, 2 H, J=8.4), 7.70 (d, 2 H, J=8.4), 7.64 (d, 2 H, J=8.4 ), 7.32 (d, 2 H, J=8.1), 6.66 (s, 1 H), 4.68 (d, 1 H, J=17.2), 4.54 (d, 1 H, J=17.2), 3.85 (m, 1 H), 3.28 (m, 2 H), 2.78 (s, 1 H), 2.40 (m, 1 H), 1.78 (m, 1 H), 1.63 (m, 2 H), 1.42–1.17 (m, 3 H), 1.12 (t, 3 H), 0.92 (m, 1 H); MS m/e 500 (M+Na)+. Reaction Reaction mixture then was washed with water (2×15 mL) Organic layer was concentrated in vacuo Residue was purified by preparatory HPLC (acetonitrile/water/trifluoroacetic acid) Acetonitrile was removed from the mixture in vacuo Remaining aqueous was frozen

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

実験手順: Cesium carbonate (1.4 mmol) was added to a solution of (1R,2S)-2-(4-Chlorobenzenesulfonylamino)-cyclohexanecarboxylic acid amide (0.62 mmol) in DMF (7 mL). 4-Chloromethyl-N-ethylbenzamide (0.76 mmol) was added to the mixture followed by potassium iodide (0.75 mmol). Reaction was stirred at room temperature overnight. Reaction mixture was diluted with ethyl acetate (20 mL) then was washed with water (2×15 mL). Organic layer was concentrated in vacuo. Residue was purified by preparatory HPLC (acetonitrile/water/trifluoroacetic acid). Proper fractions were combined. Acetonitrile was removed from the mixture in vacuo. Remaining aqueous was frozen and lyophilized to yield 4-[[(1R,2S)-(2-Carbamoyl-cyclohexyl)-(4-chlorobenzenesulfonyl)-amino]-methyl]-N-ethyl benzamide (120 mg) as a white solid in 40% yield.: 1H NMR (300 Mz, DMSO-d6) δ 8.40 (t, 1 H), 7.79 (d, 2 H, J=8.4), 7.70 (d, 2 H, J=8.4), 7.64 (d, 2 H, J=8.4 ), 7.32 (d, 2 H, J=8.1), 6.66 (s, 1 H), 4.68 (d, 1 H, J=17.2), 4.54 (d, 1 H, J=17.2), 3.85 (m, 1 H), 3.28 (m, 2 H), 2.78 (s, 1 H), 2.40 (m, 1 H), 1.78 (m, 1 H), 1.63 (m, 2 H), 1.42–1.17 (m, 3 H), 1.12 (t, 3 H), 0.92 (m, 1 H); MS m/e 500 (M+Na)+. Reaction Reaction mixture then was washed with water (2×15 mL) Organic layer was concentrated in vacuo Residue was purified by preparatory HPLC (acetonitrile/water/trifluoroacetic acid) Acetonitrile was removed from the mixture in vacuo Remaining aqueous was frozen

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

実験手順: Cesium carbonate (1.4 mmol) was added to a solution of (1R,2S)-2-(4-Chlorobenzenesulfonylamino)-cyclohexanecarboxylic acid amide (0.62 mmol) in DMF (7 mL). 4-Chloromethyl-N-ethylbenzamide (0.76 mmol) was added to the mixture followed by potassium iodide (0.75 mmol). Reaction was stirred at room temperature overnight. Reaction mixture was diluted with ethyl acetate (20 mL) then was washed with water (2×15 mL). Organic layer was concentrated in vacuo. Residue was purified by preparatory HPLC (acetonitrile/water/trifluoroacetic acid). Proper fractions were combined. Acetonitrile was removed from the mixture in vacuo. Remaining aqueous was frozen and lyophilized to yield 4-[[(1R,2S)-(2-Carbamoyl-cyclohexyl)-(4-chlorobenzenesulfonyl)-amino]-methyl]-N-ethyl benzamide (120 mg) as a white solid in 40% yield.: 1H NMR (300 Mz, DMSO-d6) δ 8.40 (t, 1 H), 7.79 (d, 2 H, J=8.4), 7.70 (d, 2 H, J=8.4), 7.64 (d, 2 H, J=8.4 ), 7.32 (d, 2 H, J=8.1), 6.66 (s, 1 H), 4.68 (d, 1 H, J=17.2), 4.54 (d, 1 H, J=17.2), 3.85 (m, 1 H), 3.28 (m, 2 H), 2.78 (s, 1 H), 2.40 (m, 1 H), 1.78 (m, 1 H), 1.63 (m, 2 H), 1.42–1.17 (m, 3 H), 1.12 (t, 3 H), 0.92 (m, 1 H); MS m/e 500 (M+Na)+. Reaction Reaction mixture then was washed with water (2×15 mL) Organic layer was concentrated in vacuo Residue was purified by preparatory HPLC (acetonitrile/water/trifluoroacetic acid) Acetonitrile was removed from the mixture in vacuo Remaining aqueous was frozen