TL-568

反应条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution (447 cc.) of sodium ethoxide in ethanol of concentration 1.34 moles per liter, followed by a solution (1,305 cc.) of ammonia in ethanol of concentration 4.6 moles per liter, are added to a suspension of N,N-bis(2-chloroethyl)-t-butylamine hydrochloride (140.7 g.) in ethanol (750 cc.). The reaction mixture is then heated at a temperature of about 60° C. for 1 hour, whilst keeping the ammonia refluxing by means of a condenser containing solid carbon dioxide. The ammonia is then allowed to dissipate, and the reaction mixture is cooled to a temperature of about 20° C. under a stream of nitrogen. A solution (894 cc.) of sodium ethoxide in ethanol of concentration 1.34 moles per liter is then added. The sodium chloride which precipitates is filtered off and then washed with ethanol (150 cc.). The filtrate is concentrated to dryness under reduced pressure and the residue obtained is taken up in diethyl ether (300 cc.). The insoluble product is filtered off and washed with diethyl ether (60 cc.). The filtrate is concentrated to dryness and then distilled under reduced pressure. 1-t.-butylpiperazine (8.8 g.), which boils at 85°-86° C. under a pressure of 28 mm.Hg, is thus obtained. the reaction mixture is cooled to a temperature of about 20° C. under a stream of nitrogen The sodium chloride which precipitates is filtered off washed with ethanol (150 cc.) The filtrate is concentrated to dryness under reduced pressure the residue obtained The insoluble product is filtered off washed with diethyl ether (60 cc.) The filtrate is concentrated to dryness distilled under reduced pressure

反应条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution (447 cc.) of sodium ethoxide in ethanol of concentration 1.34 moles per liter, followed by a solution (1,305 cc.) of ammonia in ethanol of concentration 4.6 moles per liter, are added to a suspension of N,N-bis(2-chloroethyl)-t-butylamine hydrochloride (140.7 g.) in ethanol (750 cc.). The reaction mixture is then heated at a temperature of about 60° C. for 1 hour, whilst keeping the ammonia refluxing by means of a condenser containing solid carbon dioxide. The ammonia is then allowed to dissipate, and the reaction mixture is cooled to a temperature of about 20° C. under a stream of nitrogen. A solution (894 cc.) of sodium ethoxide in ethanol of concentration 1.34 moles per liter is then added. The sodium chloride which precipitates is filtered off and then washed with ethanol (150 cc.). The filtrate is concentrated to dryness under reduced pressure and the residue obtained is taken up in diethyl ether (300 cc.). The insoluble product is filtered off and washed with diethyl ether (60 cc.). The filtrate is concentrated to dryness and then distilled under reduced pressure. 1-t.-butylpiperazine (8.8 g.), which boils at 85°-86° C. under a pressure of 28 mm.Hg, is thus obtained. the reaction mixture is cooled to a temperature of about 20° C. under a stream of nitrogen The sodium chloride which precipitates is filtered off washed with ethanol (150 cc.) The filtrate is concentrated to dryness under reduced pressure the residue obtained The insoluble product is filtered off washed with diethyl ether (60 cc.) The filtrate is concentrated to dryness distilled under reduced pressure

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

实验步骤: A mixture of 7-amino-2-(3-(trifluoromethyl)phenyl)-5H-pyrido[3,2-b]indole-4-carboxamide (90 mg, 0.243 mmol), N,N-bis(2-chloroethyl)-2-methylpropan-2-amine hydrochloride (114 mg, 0.486 mmol) and Na2CO3 (129 mg, 1.22 mmol) in t-BuOH (2 mL) was heated at reflux overnight. Purification by HPLC gave 7-(4-tert-butylpiperazin-1-yl)-2-(3-(trifluoromethyl)phenyl)-5H-pyrido[3,2-b]indole-4-carboxamide (40 mg, 0.077 mmol, 32% yield). MS (ESI) m/z 496.2 (M+H). 1H NMR (500 MHz, DMSO-d6) δ ppm 11.30 (1H, s), 8.60 (2H, d, J=1.53 Hz), 8.56 (1H, br. s.), 8.40 (1H, s), 8.07 (1H, d, J=8.55 Hz), 7.85 (1H, br. s.), 7.74-7.78 (2H, m), 7.20 (1H, d, J=1.83 Hz), 7.00 (1H, dd, J=8.85, 2.14 Hz), 3.23-3.28 (4H, m), 2.71 (4H, d, J=4.27 Hz), 1.08 (9H, s). was heated at reflux overnight Purification by HPLC

反应条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution (447 cc.) of sodium ethoxide in ethanol of concentration 1.34 moles per liter, followed by a solution (1,305 cc.) of ammonia in ethanol of concentration 4.6 moles per liter, are added to a suspension of N,N-bis(2-chloroethyl)-t-butylamine hydrochloride (140.7 g.) in ethanol (750 cc.). The reaction mixture is then heated at a temperature of about 60° C. for 1 hour, whilst keeping the ammonia refluxing by means of a condenser containing solid carbon dioxide. The ammonia is then allowed to dissipate, and the reaction mixture is cooled to a temperature of about 20° C. under a stream of nitrogen. A solution (894 cc.) of sodium ethoxide in ethanol of concentration 1.34 moles per liter is then added. The sodium chloride which precipitates is filtered off and then washed with ethanol (150 cc.). The filtrate is concentrated to dryness under reduced pressure and the residue obtained is taken up in diethyl ether (300 cc.). The insoluble product is filtered off and washed with diethyl ether (60 cc.). The filtrate is concentrated to dryness and then distilled under reduced pressure. 1-t.-butylpiperazine (8.8 g.), which boils at 85°-86° C. under a pressure of 28 mm.Hg, is thus obtained. the reaction mixture is cooled to a temperature of about 20° C. under a stream of nitrogen The sodium chloride which precipitates is filtered off washed with ethanol (150 cc.) The filtrate is concentrated to dryness under reduced pressure the residue obtained The insoluble product is filtered off washed with diethyl ether (60 cc.) The filtrate is concentrated to dryness distilled under reduced pressure