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(a) Preparation of amino([(2-nitrophenyl)methyl]amino)-methane-1-thione.To a solution of <strong>[24835-08-3]2-nitrobenzylamine hydrochloride</strong> (Avocado) (4.93 g, 26.1 mmol) and Et3N (10 ML, 71.8 mmol) in CHCl3 (300 ML) was added benzoyl isothiocyanate (Aldrich) (3.4 ML, 25.3 mmol) and the resulting yellow solution was heated to 61 C. After 1.5 h the solvent was removed in vacuo and the residue was dissolved in 70% aqueous MeOH. To the solution was added K2CO3 (4.06 g, 29.4 mmol) and the reaction was heated at reflux for 0.5 h.The yellow-orange mixture was cooled to RT and the crude material was purified by flash chromatography on silica gel with Hexanes:EtOAc (4:1, 1:1, 1:3) as eluant to afford a purple solid. Mp: 228-229 C. MS m/z: 212 (M+1). Calc'd for C8H9N3O2S-211.04.
With sodium cyanoborohydride; In methanol; at 0 - 20℃; for 3h;
Example 2; [00281] [N-methyl-N-2-((tert-butoxycarbonylisopropylamino)methyl)phenyl]carbamic acid 1-chloro-ethyl ester [00282]; a) Preparation of Isopropyl-(2-nitro-benzyl)-carbamic acid tert-butyl ester; [00283] To a mixture of <strong>[24835-08-3]2-nitrobenzylamine hydrochloride</strong> (500 mg, 2.65 mmol) and acetone (0.39 ml, 5.30 mmol) in methanol (13 ml) was added sodium cyanoborohydride (500 mg, 7.95 mmol) at 0 C. The temperature was warm up to room temperature. After stirring for 3 hr, the mixture was concentrated in vacuo and extracted with dichloromethane. The combined organic phase was washed with water and brine, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to give N-isopropyl-2-nitrobenzylamine as yellow oil. This compound was used in next step without further purification. [00284] To a mixture of N-isopropyl-2-nitrobenzylamine and N,N-diisopropylethyl amine (1.15 ml, 6.63 mmol) in tetrahydrofuran (20 ml) was added di-tert-butyl dicarbonate (1.22 ml, 5.30 mmol) at room temperature. After stirring overnight, the mixture was quenched with water and extracted with ethyl acetate. The combined: organic phase was washed with water and brine, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography (15% ethyl acetate-hexane) to afford isopropyl-(2-nitro-benzyl)-carbamic acid tert-butyl ester (e) (736 mg, 2.50 mmol, 94%) as light yellow oil.
dimethyl 2-6-dimethyl-1-(2-nitrobenzyl)-4-(3-nitrophenyl)-1,4-dihyrdo-pyridine-3,5-dicarboxylate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
1.7 g (18%)
In pyridine;
Example 1 Dimethyl 2,6-dimethyl-1-(2-nitrobenzyl)-4-(3-nitrophenyl)-1,4-dihydro-pyridine-3,5-dicarboxylate STR16 A mixture of 3 g (20 mmol) 3-nitrobenzaldehyde, 4.6 g (40 mmol) methyl acetoacetate and 3.7 g (20 mmol) 2-nitrobenzylamine HCl in 20 ml pyridine is heated for 6 h under reflux. After cooling the mixture is poured into water, extracted with CH2 Cl2, died and the solvent removed. Chromatography yielded 1.7 g (18%) of dimethyl 2-6-dimethyl-1-(2-nitrobenzyl)-4-(3-nitrophenyl)-1,4-dihyrdo-pyridine-3,5-dicarboxylate (mp: 180 C.).
With hydrogenchloride; sodium hydroxide; sodium sulfate; In ethanol; water;
EXAMPLE 7 Ethyl β-(o-Nitrobenzylamino)-propionate (see J.A.C.S., 80, 1168 (1958) o-Nitrobenzylamine hydrochloride (20.4 g., 0.114 mole) was dissolved in a minimum volume of water and the solution was made strongly basic by addition of 10% sodium hydroxide. The clear oil which formed was extracted into two 120-ml. portions of ether. The ether was dried with 10 g. of anhydrous sodium sulfate, filtered, and finally dried over Drierite. The dried solution was filtered and evaporated, leaving a yellow oil. The oil was dissolved in 100 ml. of absolute ethanol and 11.4 g (0.114 mole) of freshly distilled ethyl acrylate was added. This solution was allowed to stand overnight and the solvent removed by distillation from a steam-cone. The oily residue was dissolved in 200 ml. of dry ether, the solution was cooled in an ice bath, and treated with dry hydrogen chloride. When precipitation was complete, the solid was filtered and dissolved in 120 ml. of boiling absolute ethanol. The hydrochloride crystallized from this solution on cooling yielding 20.7 g. of the aminopropionate hydrochloride, m.p. 137.5-139.0. By concentrating and cooling the mother liquor, an additional 5 g. was obtained, m.p. 136.5-138.5, and by repeating this operation 1.1 g., m.p. 136-139, was obtained, raising the total yield to 26.8 g. (81.4%). The analytical sample was prepared by repeated crystallization from absolute ethanol to give a melting point of 138.5-139.0. Anal. calc'd. for C12 H17 O4 N2 Cl: C, 49.91; H, 5.94; N, 9.70. Found: C, 49.9; H, 5.94; N, 9.51.
With hydrogenchloride; sodium hydroxide; sodium sulfate; In ethanol; water;
EXAMPLE 7 Ethyl β-(o-Nitrobenzylamino)-propionate (see J.A.C.S., 80, 1168 (1958) o-Nitrobenzylamine hydrochloride (20.4 g., 0.114 mole) was dissolved in a minimum volume of water and the solution was made strongly basic by addition of 10% sodium hydroxide. The clear oil which formed was extracted into two 120-ml. portions of ether. The ether was dried with 10 g. of anhydrous sodium sulfate, filtered, and finally dried over Drierite. The dried solution was filtered and evaporated, leaving a yellow oil. The oil was dissolved in 100 ml. of absolute ethanol and 11.4 g (0.114 mole) of freshly distilled ethyl acrylate was added. This solution was allowed to stand overnight and the solvent removed by distillation from a steam-cone. The oily residue was dissolved in 200 ml. of dry ether, the solution was cooled in an ice bath, and treated with dry hydrogen chloride. When precipitation was complete, the solid was filtered and dissolved in 120 ml. of boiling absolute ethanol. The hydrochloride crystallized from this solution on cooling yielding 20.7 g. of the aminopropionate hydrochloride, m.p. 137.5-139.0. By concentrating and cooling the mother liquor, an additional 5 g. was obtained, m.p. 136.5-138.5, and by repeating this operation 1.1 g., m.p. 136-139, was obtained, raising the total yield to 26.8 g. (81.4%). The analytical sample was prepared by repeated crystallization from absolute ethanol to give a melting point of 138.5-139.0. Anal. calc'd. for C12 H17 O4 N2 Cl: C, 49.91; H, 5.94; N, 9.70. Found: C, 49.9; H, 5.94; N, 9.51. SPC26
31. tert-Butyl 4-r(2-nitrobenzyl)amino1piperidine- 1 -carboxylate; To a mixture of <strong>[24835-08-3]2-nitrobenzylamine hydrochloride</strong> (20.0 g, 106.0 mmol) in DCE (250 mL) is added TEA (10.73 g, 106.0 mmol). The mixture is allowed to stir at rt for 5 min. To this mixture N-Boc-4-piperidone (21.13 g, 106.0 mmol), and HOAC (7.96 g, 132.5 mmol), is added and stirred at rt for another 5 min. NaBH(OAc)3 (25.28 g, 119.3 mmol) is added in portions and the mixture is stirred at rt for 1 hr before it is washed with 10 % Na2CO3 solution (100 mL x 3) and brine (50 mL x 2). The organic phase is dried over Na2SO4. The solvent is removed in vacuo to afford the title compound as a red oil, which is used without further purification in subsequent steps.
18. tert-Butyl 4-r(2-nitrobenzyl)aminolρiρeridine-l -carboxvlate; To a mixture of <strong>[24835-08-3]2-nitrobenzylamine hydrochloride</strong> (20.0 g, 106.0 mmol) in DCE (250 mL) is added TEA (10.73 g, 106.0 mmol). The mixture is allowed to stir at rt for 5 min. To this mixture N-Boc-4-piperidone (21.13 g, 106.0 mmol), and HOAC (7.96 g, 132.5 mmol), is added and stirred at rt for another 5 min. NaBH(OAc)3 (25.28 g, 119.3 mmol) is added in portions and the mixture is stirred at rt for 1 hr before it is washed with 10 % Na2CO3 solution (100 mL * 3) <n="59"/>and brine (50 mL x 2). The organic phase is dried over Na2SCU- The solvent is removed in vacuo to afford the title compound as a red oil, which is used without further purification in subsequent steps.
With triethylamine; 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride; In tetrahydrofuran; at 0 - 20℃; for 5h;
2-Nitrobenzyl amine hydrochloride (2.27 g, 12.0 mmol), 3-hydroxy-3-phenyl propionic acid (2.00 g, 12.0 mmol), triethylamine (1.34 g, 13.3 mmol) were added to tetrahydrofuran (50 ml) and the reaction mixture was ice cooled. Under ice cooled condition, 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (3.33 g, 12.0 mmol) was added thereto and stirred at room temperature for five hours. The reaction mixture was poured into dilute hydrochloric acid water and extracted with ethyl acetate. The organic layer was washed with a saturated brine and then dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The obtained crude crystal was washed with a mixture of hexane-ether (2:1) to obtain 3-hydroxy-N-(2-nitrobenzyl)-3-phenyl propionic acid amide (3.32 g). Yield: 92% Physical properties: Melting point 145.1C
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