药物Deutetrabenazine（氘代丁苯那嗪）合成检索总
结报告
一、Deutetrabenazine（氘代丁苯那嗪）简介
Deutetrabenazine（氘代丁苯那嗪）于2017年4月在美国上市，主要用于治疗与亨廷顿病相关的舞蹈病。Deutetrabenazine（氘代丁苯那嗪）不良反应有心悸、烦躁、嗜睡、腹泻、口干、疲劳、加重帕金森病等等。
吸血鬼日记第2季Deutetrabenazine（氘代丁苯那嗪）分子结构式如下:
CAS:1392826-25-3
英文名称：Deutetrabenazine
中文名称：氘代丁苯那嗪
illusions
姿态的意思二、Deutetrabenazine（氘代丁苯那嗪）合成路线
三、Deutetrabenazine（氘代丁苯那嗪）合成检索总结报告
(一)Deutetrabenazine（氘代丁苯那嗪）中间体2的合成方法一
兔子的英文单词合成方法
实验步骤参考文献操作方法
一
atopi
Dopamine hydrochloride
1(250.0g,1.323mol,1.0eq)was suspended in ethyl formate (2.5L,10.0vol)at 25-30°C.The suspension was cooled to 10-15°C.and sodium tert-butoxide (202g,2.12mol,1.60eq)was added portionwi maintaining the same temperature.The reaction mixture was warmed to 55-60°C.for 12hours and then concentrated under reduced pressure.To the remaining residue,water (125mL,0.5vol)was added and stirred for 15minutes.The volatile organic solvents were distilled under vacuum whereupon the product precipitated.The suspension was cooled to 25-30°C.and purified water (500mL,2.0vol)was added.The solid was filtered and washed with water (125mL,0.5vol)and dried in an oven at 55-60°C.for 8hours to afford the title compound 2as a brown powder (203g,yield=84.5%).US2015/152099;(2015);(A1)English 操作方法
二Triethylamine (110.0mL,789.21mmol)was added to a suspension of 4-(2-aminoethyl)benzene-l,2-diol hydrochloride 1(100.0g,527.31mmol)in ethyl formate (500mL)at 0°C.Reaction mixture was stirred at 55°C for 15hours.After completion of reaction (monitored by TLC)excess ethyl formate was removed under reduced pressure at 45°C.The resulting residue was diluted with water (500mL)and stirred at room temperature for 1hour.The solid parated was filtered off and washed with water (3×100mL).Isolated solid was dried at 65°C for 12hours yielding 62.0g pure N-(3,4-dihydroxyphenethyl)formamide 2as a beige solid (Yield:65%).Purity by HPLC:99%.WO2019/150387;(2019);(A1)English
(二)Deutetrabenazine （氘代丁苯那嗪）中间体2的合成方法二合成方法实验步骤
参考文献Potassium carbonate (7.7g,0.055moles)was slowly added to a mixture of dopamine hydrochloride 1(10.0g,0.053moles)in toluene (60mL)while stirring the reaction mixture at 25°C -35°C.Stirring was continued for 45-60minutes,then formic acid (5.7g,0.124mol)was slowly added at sally
25°C -35°C.The reaction suspension was heated to 95°C -
WO2019/130252;
koka操作方法
一100°C and maintained at that temperaturererved
for 17hours.Reaction progress was checked by measuring prence of the starting material by TLC/HPLC.The reaction mixture was concentrated under reduced pressure at 45°C -50°C.Water (20mL)was added to the residue and the mixture was stirred for 1-2hours at room temperature.The reaction mixture was filtered and the solid was washed with water and dried in vacuum oven at 55°C for 15hours to get N-[2-(3,4-dihy-droxyphenyl)ethyl]formamide 2.
(2019);(A2)English (三)Deutetrabenazine （氘代丁苯那嗪）中间体2的合成方法三合成方法
实验步骤参考文献操作方法
dewen
一Triethylamine (3.66mL,
26.37mmol)was added to dopamine hydrochloride 1(5.0g,26.37mmol)in methyl formate (60mL)and the stirred brown solution was heated to reflux for 32h.The reaction mixture was cooled to rt,diluted with ethyl acetate (100mL)and washed withhydrochloric acid (2M;3×50mL),water (50mL)and brine (50mL).The organic phawas dried (MgSO 4)and concentrated to give the title compound 2as a pink-brown solid that did not require further purification (1.19g,25%);mp 126-128°C.Synlett ;vol.27;nb.1;(2016);p.37–40.
(四)Deutetrabenazine （氘代丁苯那嗪）中间体3的合成合成方法
实验步骤参考文献操作方法
一D 4-Methanol (25.0g,693.1mmol)was added to a solution of N-(3,4-dihydroxyphenethyl)formamide 2(25.0g,137.98mmol)and triphenylphosphine (109.0g,415.6mmol)in dry THE at 0°C under nitrogen.DIAD (85.0g,420.35mmol)was added to reaction mixture at 0°C under nitrogen.Reaction mixture stirred at room temperature for 15h.After completion of reaction (monitored by TLC),reaction mixture concentrated under reduced pressure at 45°C.The resulting crude was purified by column chromatography on silica gel,eluting with 5%MeOH in MDC,yielding 20g pure D 6-N-(3,4-dimethoxyphenethyl)formamide 3as a Pale
WO2019/150387;(2019);(A1)English
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