CN113292503B - 一种2-溴-3-胺基萘醌化合物的制备方法 - Google Patents

一种2-溴-3-胺基萘醌化合物的制备方法 Download PDF

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CN113292503B
CN113292503B CN202110576100.9A CN202110576100A CN113292503B CN 113292503 B CN113292503 B CN 113292503B CN 202110576100 A CN202110576100 A CN 202110576100A CN 113292503 B CN113292503 B CN 113292503B
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应小明
赵佳佳
吴戈
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First Peoples Hospital Taizhou
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Abstract

本发明涉及一种2‑溴‑3‑胺基萘醌化合物的制备方法,在有机溶剂中,氮气条件下,以N‑溴代丁二酰亚胺、仲胺和萘醌为反应原料,利用原位生成的溴胺化试剂,通过自由基串联反应得到2‑溴‑3‑胺基萘醌化合物。所述方法反应条件简单、产物的产率和纯度高,为2‑溴‑3‑胺基萘醌化合物的制备开拓了合成路线和方法,具有良好的应用潜力和研究价值。

Description

一种2-溴-3-胺基萘醌化合物的制备方法
技术领域
本发明属于有机化合物合成技术领域,尤其是涉及一种2-溴-3-胺基萘醌化合物的制备方法。
背景技术
2-溴-3-胺基萘醌作为核心骨架广泛存应用于具有重要生物活性候癌药物合成中。例如:
Figure BSA0000243097250000012
N.da Silva Júnicra课题组利用2-溴-胺基萘醌,通过click反应合成三氮唑衍生物,通过抗肿瘤生物活性发现此类化合物的IC50<0.3μM(European Journal ofMedicinal Chemistry,2016,122,1-16);2-溴-3-胺基萘醌中间体通过经典的Sonogashira偶联反应合成氮杂环萘醌化合物(Russ Chem Bull,2012,61,582-588)或者Buchwald-Hartwig反应(Synlett 2015,26,2429-2433);与有机胺的亲核取代反应合成2,3-双胺化萘醌衍生物(Tetrahedron Letters,2009,50,5896-5902);另外,制备的5,6,8,13-四氢-7-萘酚[2,3-a][3]-苯并氮杂-8,13-二酮表现出IC50=3.5μg/mL的肝癌细胞抑制活性(ArchPharm Res,2012,35,769-777)。值得一提的是,合成2-溴-3-胺基萘醌化合物的方法需要分步合成策略,需要使用强腐蚀性的液溴(Journal of Materials Chemistry A,2017,5,5495-5501)或者是利用2,3-二溴-1,4-萘二酚为起始原料合成2,3-二溴萘醌(TetrahedronLetters,2017,58,2294-2297),然后与有机胺通过亲核取代反应合成目标化合物,尽管取得了很大的研究进展,但这些策略存在官能团兼容性差,合成步骤繁琐,不利于药物分子后期修饰等缺点,发展萘醌的直接双官能团方法可以使合成更加线性化,为复杂小分子的后期修饰提供强有力的工具。
最近,吴戈课题组利用原位生成的胺卤化试剂作为双官能团化试剂,实现了铜催化马来酰亚胺的胺卤化反应(Haloamines ad Bifunctional Reagents for OxidativeAminohalogenation of Maleimides,Organic Letters,2021,23,3669-3673)。考虑到2-溴-3胺基萘醌结构在创新药物研发中的重要性,因此,利用简便、易于处理的实验操作条件、底物廉价易得的原料来制备2-溴-3-胺基萘醌化合物的反应显得尤为重要,尤其是利用原位生成的溴胺化试剂实现2-溴-3-胺基萘醌化合物的反应,至今未曾报道,仍存在继续进行研究和探索的必要,这也是本发明得以完成的基础和动力所在。
发明内容
本发明所要解决的技术问题是2-溴-3-胺基萘醌化合物的制备方法的合成路线问题。
为解决以上技术问题,本发明提供下述技术方案:
一种2-溴-3-胺基萘醌化合物的制备方法,在有机溶剂中,氮气条件下,以N-溴代丁二酰亚胺,仲胺和萘醌为反应原料,利用原位生成的溴胺化试剂,通过自由基串联反应得到2-溴-3-胺基萘醌化合物;
上述的反应过程,可用下述的反应式表示:
Figure BSA0000243097250000011
所述N-溴代丁二酰亚胺、仲胺和萘醌的摩尔比为3∶3∶1。
(1)有机溶剂
本发明中的反应溶剂为有机溶剂,所述有机溶剂为二甲基亚砜、N,N-二甲基甲酰胺、1,4-二氧六烷、1,2-二氯乙烷、乙腈、甲苯、四氢呋喃中的至少一种,优选乙腈。
(2)反应温度
本发明的制备方法中,反应温度为室温25℃。
(3)反应时间
在本发明的制备方法中,反应时间为20分钟。
(5)分离纯化
在一种优选的实施方式中,反应结束后的后处理步骤可为如下方法:反应结束后,将反应液冷却后加入乙酸乙酯稀释,将有机相过滤至鸡心瓶,然后旋掉溶剂,将浓缩物通过柱色谱分离,以石油醚和乙酸乙酯混合液为洗脱剂,收集洗脱液,浓缩后得到目标产物。
本发明提供的2-溴-3-胺基萘醌化合物的制备方法具有如下有益效果;
a)反应条件温和,快速;
b)利用原位生成的溴胺化试剂为双官能团化试剂;
c)实验操作简单,产率产率高;
本发明以N-溴代丁二酰亚胺、仲胺和萘醌为反应原料,氮气条件下,利用原位生成的溴胺化试剂,通过自由基串联反应得到2-溴-3-胺基萘醌化合物。本发明反应原料廉价易得、产物的产率和纯度高,为2-溴-3-胺基萘醌化合物的制备开拓了合成路线和方法,为双取代马来酰亚胺衍生物的分子设计与合成提供新思路,具有重要的社会意义和经济意义。
具体实施方式
下面通过具体的实施例对本发明进行详细说明,但这些例举性实施方式的用途和目的仅用来例举本发明,并非对本发明的实际保护范围构成任何形式的任何限定,更非将本发明的保护范围局限于此。
以下实施例所给出的新化合物的数据和纯度均通过核磁共振鉴定。
实施1:
2-溴-3-(2-(1-哌嗪基)哌嗪嘧啶基)萘醌化合物的合成
Figure BSA0000243097250000021
在室温下,将萘醌(0.2mmol,1.0equiv)、N-溴代丁二酰亚胺(0.6mmol,3.0equiv)和2mL乙腈加入到反应管中,然后加入1-(2-嘧啶基)哌嗪(0.6mmol,3.0equiv)、抽气-充氮气置换三次,室温搅拌20分钟。加入乙酸乙酯进行稀释,将有机相过滤至鸡心瓶,旋掉有机溶剂,经柱层析分离得到产物(洗脱剂:石油醚∶乙酸乙酯为9∶1),产物为紫黑色固体,熔点为131-132℃,收率81%,产物重量为64mg。
所得产物的核磁共振氢谱的数据如下:
1H NMR(500MHz,CDCl3):δ8.36(d,J=4.8Hz,2H),8.13(d,J=7.0Hz,1H),8.04(d,J=8.5Hz,1H),7.73-7.69(m,2H),6.56(t,J=4.8Hz,1H),4.05(q,J=4.7Hz,4H),3.70-3.67(m,4H);
所得产物的核磁共振碳谱的数据如下:
13C NMR(125MHz,CDCl3):δ181.6,178.2,161.6,157.9,152.9,134.2,133.2,131.5,131.4,127.1,127.0,117.9,110.4,51.7,44.7;
所得产物的高分辨质谱数据如下:
HRMS(ESI):calcd for C18H16N4O2Br[M+H]+399.0457,found 399.0453.
实施2:
2-溴-3-(4-叔丁氧羰基氨基哌啶基)萘醌化合物的合成
Figure BSA0000243097250000022
在室温下,将萘醌(0.2mmol,1.0equiv)、N-溴代丁二酰亚胺(0.6mmol,3.0equiv)和2mL乙腈加入到反应管中,然后加入4-叔丁氧羰基氨基哌啶(0.6mmol,3.0equiv)、抽气-充氮气置换三次,室温搅拌20分钟。加入乙酸乙酯进行稀释,将有机相过滤至鸡心瓶,旋掉有机溶剂,经柱层析分离得到产物(洗脱剂:石油醚∶乙酸乙酯为9∶1),产物为紫黑色固体,熔点为113-114℃,收率77%,产物重量为66mg。
所得产物的核磁共振氢谱的数据如下:
1H NMR(500MHz,CDCl3):δ8.14(dd,J=7.3,1.7Hz,1H),8.03(dd,J=7.1,1.9Hz,1H),7.71(pd,J=7.4,1.6Hz,2H),4.58(brs,1H),3.84-3.78(m,3H),3.39(ddd,J=13.8,11.3,2.6Hz,2H),2.11(dd,J=13.5,3.4Hz,2H),1.71-1.63(m,2H),1.49(s,9H);
所得产物的核磁共振碳谱的数据如下:
13C NMR(125MHz,CDCl3):δ182.0,178.1,155.2,150.5,134.1,133.2,131.7,131.5,126.9,126.8,126.7,50.6,48.3,33.5,32.3,28.5;
所得产物的高分辨质谱数据如下:
HRMS(ESI):calcd for C20H23N2O4NaBr[M+Na]+457.0739,found 457.0732.
实施3:
2-溴-3-(1-乙酰基哌啶基)萘醌化合物的合成
Figure BSA0000243097250000031
在室温下,将萘醌(0.2mmol,1.0equiv)、N-溴代丁二酰亚胺(0.6mmol,3.0equiv)和2mL乙腈加入到反应管中,然后加入1-乙酰哌嗪(0.6mmol,3.0equiv)、抽气-充氮气置换三次,室温搅拌20分钟。加入乙酸乙酯进行稀释,将有机相过滤至鸡心瓶,旋掉有机溶剂,经柱层析分离得到产物(洗脱剂:石油醚∶乙酸乙酯为9∶1),产物为紫黑色固体,熔点为70-71℃,收率91%,产物重量为66mg。
所得产物的核磁共振氢谱的数据如下:
1H NMR(500MHz,CDCl3):δ8.17(dd,J=7.3,1.7Hz,1H),8.07(dd,J=7.1,1.9Hz,1H),7.74(pd,J=7.4,1.6Hz,2H),3.84-3.61(m,8H),2.20(s,3H);
所得产物的核磁共振碳谱的数据如下:
13C NMR(125MHz,CDCl3):δ181.6,178.3,169.3,152.7,134.3,133.5,131.3,131.2,127.1,120.0,119.4,51.6,42.3,21.4;
所得产物的高分辨质谱数据如下:
HRMS(ESI):calcd for C16H15N2O3NaBr[M+Na]+385.0164,found 385.0155.
实施4:
2-溴-3-(4-哌啶甲酸甲酯基)萘醌化合物的合成.
Figure BSA0000243097250000032
在室温下,将萘醌(0.2mmol,1.0equiv)、N-溴代丁二酰亚胺(0.6mmol,3.0equiv)和2mL乙腈加入到反应管中,然后加入4-哌啶甲酸甲酯(0.6mmol,3.0equiv)、抽气-充氮气置换三次,室温搅拌20分钟。加入乙酸乙酯进行稀释,将有机相过滤至鸡心瓶,旋掉有机溶剂,经柱层析分离得到产物(洗脱剂:石油醚∶乙酸乙酯为9∶1),产物为紫黑色液体,收率90%,产物重量为68mg。
所得产物的核磁共振氢谱的数据如下:
1H NMR(500MHz,CDCl3):δ8.14(dd,J=7.3,1.7Hz,1H),8.02(dd,J=7.1,1.9Hz,1H),7.70(pd,J=7.4,1.6Hz,2H),3.83(dd,J=13.3,4.1Hz,2H),3.75(s,3H),3.39(ddd,J=13.5,10.5,3.2Hz,2H),2.64(tt,J=10.0,4.4Hz,1H),2.05(pd,J=10.4,9.8,3.6Hz,4H);
所得产物的核磁共振碳谱的数据如下:
13C NMR(125MHz,CDCl3):δ181.7,178.3,174.9,153.3,134.1,133.2,131.5,131.4,127.0,126.9,117.8,51.9,51.5,40.6,28.9;
所得产物的高分辨质谱数据如下:
HRMS(ESI):calcd for C17H16N04NaBr[M+Na]+400.0160,found 400.0154.
实施5:
2-溴-3-(4-羟基哌啶基)萘醌化合物的合成
Figure BSA0000243097250000041
在室温下,将萘醌(0.2mmol,1.0equiv)、N-溴代丁二酰亚胺(0.6mmol,3.0equiv)和2mL乙腈加入到反应管中,然后加入4-羟基哌啶(0.6mmol,3.0equiv)、抽气-充氮气置换三次,室温搅拌20分钟。加入乙酸乙酯进行稀释,将有机相过滤至鸡心瓶,旋掉有机溶剂,经柱层析分离得到产物(洗脱剂:石油醚∶乙酸乙酯为9∶1),产物为紫黑色固体,熔点为115-116℃,收率77%,产物重量为51mg。
所得产物的核磁共振氢谱的数据如下:
1H NMR(400MHz,CDCl3):δ8.11(dd,J=6.8,2.1Hz,1H),8.01(dd,J=6.7,2.1Hz,1H),7.69(tt,J=7.4,5.7Hz,2H),4.03(tt,J=8.3,3.9Hz,1H),3.83(dt,J=13.6,4.7Hz,2H),3.44(ddd,J=13.0,9.2,3.2Hz,2H),2.14-2.06(m,3H),1.83(dtd,J=12.7,8.9,3.7Hz,2H);
所得产物的核磁共振碳谱的数据如下:
13C NMR(100MHz,CDCl3):δ181.7,178.3,153.4,134.1,133.1,131.5,131.4,127.0,126.9,117.1,67.1,49.5,35.2;
所得产物的高分辨质谱数据如下:
HRMS(ESI):calcd for C15H14NO3NaBr[M+Na]+358.0055,found 358.0061.
实施6:
2-溴-3-(3-哌啶甲酸乙酯基)萘醌化合物的合成
Figure BSA0000243097250000042
在室温下,将萘醌(0.2mmol,1.0equiv)、N-溴代丁二酰亚胺(0.6mmol,3.0equiv)和2mL乙腈加入到反应管中,然后加入3-哌啶甲酸乙酯(0.6mmol,3.0equiv)、抽气-充氮气置换三次,室温搅拌20分钟。加入乙酸乙酯进行稀释,将有机相过滤至鸡心瓶,旋掉有机溶剂,经柱层析分离得到产物(洗脱剂:石油醚∶乙酸乙酯为9∶1),产物为紫黑色液体,收率90%,产物重量为70mg。
所得产物的核磁共振氢谱的数据如下:
1H NMR(400MHz,CDCl3):δ8.15-8.13(m,1H),8.05-8.02(m,1H),7.74-7.67(m,2H),4.17(q,J=7.1Hz,2H),3.97-3.92(m,1H),3.68-3.63(m,1H),3.47(dd,J=13.2,9.8Hz,1H),3.39(ddd,J=13.4,10.2,3.3Hz,1H),2.86(ddd,J=10.0,5.9,3.9Hz,1H),2.18-2.16(m,1H),1.95-1.92(m,1H),1.81(ddd,J=11.0,6.4,2.8Hz,2H),1.26(t,J=7.1Hz,3H);
所得产物的核磁共振碳谱的数据如下:
13C NMR(100MHz,CDCl3):δ181.6,178.3,173.2,153.4,134.1,133.2,131.5,131.4,127.1,126.9,118.3,60.7,53.8,52.5,42.3,26.9,25.3,14.3;
所得产物的高分辨质谱数据如下:
HRMS(ESI):calcd for C18H18NO4NaBr[M+Na]+414.0317,found 414.0311.
由上述实施例1-6可看出,当采用本发明的所述方法时,能够以高产率、高纯度得到2-溴-3-胺基萘醌化合物。
实施例7-12
除将其中的有机溶剂乙腈分别替换为如下的有机溶剂外,以与实施例1相同的方式而分别实施了实施7-12,所使用有机溶剂和相应产物的收率如下表2所示。
表2
编号 溶剂 反应产率(%)
实施例7 N,N-二甲基甲酰胺 11
实施例8 二甲亚砜 24
实施例9 1,4-二氧六烷 77
实施例10 1,2-二氯乙烷 50
实施例11 甲苯 88
实施例12 四氢呋喃 71
由上表2可看出,反应溶剂不是很敏感,无论是强极性溶剂还是非极性溶剂,均能够顺利地进行,然而在乙腈溶剂中,产物的产率是最高的。
综上所述,由上述所有实施例可明确看出,当采用本发明的方法使用合适的有机溶剂乙腈时,使得N-溴代丁二酰亚胺、仲胺和萘醌,在氮气条件下,利用原位生成的胺溴化试剂,通过自由基串联反应以高产率和高纯度合成得到2-溴-3-胺基萘醌化合物,为该类化合物的高效快捷合成提供了全新的合成路线。
最后应说明的是:以上各实施例仅用以说明本发明的技术方案,而非对其限制;尽管参照前述各实施例对本发明进行了详细的说明,本领域的普通技术人员应当理解:其依然科研对前述各实施例所记载的技术方案进行修改,或者对其中部分或者全部技术特征进行等同替换;而这些修改或者替换,并不使相应技术方案的本质脱离本发明各实施例技术方案的范围。

Claims (4)

1.一种2-溴-3-胺基萘醌化合物的制备方法,其特征在于,在有机溶剂中,氮气条件下,以N-溴代丁二酰亚胺、仲胺和萘醌为反应原料,利用原位生成的溴胺化试剂,通过自由基串联反应得到2-溴-3-胺基萘醌化合物;
Figure FSA0000243097240000011
所述有机溶剂为乙腈。
2.根据权利要求1所述的制备方法,其特征在于,所述N-溴代丁二酰亚胺、仲胺和萘醌的摩尔比为3∶3∶1。
3.根据权利要求1所述的制备方法,其特征在于,反应温度为25℃。
4.根据权利要求1所述的制备方法,其特征在于,反应时间为20分钟。
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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5292873A (en) * 1989-11-29 1994-03-08 The Research Foundation Of State University Of New York Nucleic acids labeled with naphthoquinone probe
WO2004043912A3 (en) * 2002-11-06 2004-07-01 Bristol Myers Squibb Co Methods for the preparation of pyrrolotriazine compounds useful as kinase inhibitors
WO2007026041A2 (es) * 2005-09-02 2007-03-08 Consejo Superior De Investigaciones Cientificas Compuestos 1,4 antraquinonicos, su procedimiento de obtencion y su aplicacion como antiumorales.
US20080015221A1 (en) * 2006-07-14 2008-01-17 Jui-I Chao Compound capable of cytoskeleton and induction of cell elongation and process for synthesizing the same
CN101993446A (zh) * 2009-08-13 2011-03-30 中国科学院上海药物研究所 一类新型苯并蒽环类化合物及其制备方法和用途

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5292873A (en) * 1989-11-29 1994-03-08 The Research Foundation Of State University Of New York Nucleic acids labeled with naphthoquinone probe
WO2004043912A3 (en) * 2002-11-06 2004-07-01 Bristol Myers Squibb Co Methods for the preparation of pyrrolotriazine compounds useful as kinase inhibitors
WO2007026041A2 (es) * 2005-09-02 2007-03-08 Consejo Superior De Investigaciones Cientificas Compuestos 1,4 antraquinonicos, su procedimiento de obtencion y su aplicacion como antiumorales.
US20080015221A1 (en) * 2006-07-14 2008-01-17 Jui-I Chao Compound capable of cytoskeleton and induction of cell elongation and process for synthesizing the same
CN101993446A (zh) * 2009-08-13 2011-03-30 中国科学院上海药物研究所 一类新型苯并蒽环类化合物及其制备方法和用途

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