CN107325018A - β‑三氟甲基烯胺衍生物及其制备方法 - Google Patents
β‑三氟甲基烯胺衍生物及其制备方法 Download PDFInfo
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Abstract
本发明涉及一种β‑三氟甲基烯胺衍生物,其结构通式如下:其中,R1、R2、R3、R4、R5、R6、R7、R8、R9、R10独立地选自氢、烷基、烷氧基、卤素或三氟甲基。本发明还提供了一种上述β‑三氟甲基烯胺衍生物的制备方法,包括以下步骤:将取代N‑(2‑苯基‑1‑乙烯基)苯甲酰胺衍生物和tongi试剂在碱、配体和铜盐催化剂的作用下在有机溶剂中于80‑100℃下反应,得到β‑三氟甲基烯胺衍生物。本发明的方法可以高收率的得到多种β‑三氟甲基烯胺衍生物;反应条件温和、操作和后处理过程简单,适合于规模化生产。
Description
技术领域
本发明涉及有机化学领域,尤其涉及一种β-三氟甲基烯胺衍生物及其制备方法。
背景技术
三氟甲基是许多农业化学品和药物中非常重要的结构基序,因为它能有效改善生物活性化合物的物理和化学性质,如膜渗透性,生物利用度和代谢稳定性。同时,具有β-三氟甲基的胺类化合物是许多生物活性化合物中重要的结构基序,也是合成氟化氨基酸和肽酶的有用中间体。因此,开发合成β-三氟甲基胺类化合物及其衍生物的方法具有非常重要的意义。
目前,β-三氟甲基烯胺衍生物的合成方法主要有以下几种:
(1)在光的催化下,三氟甲基磺酰氯与末端烯胺反应得到三氟甲基化产物。该方法仅适合末端烯胺的三氟甲基化。(2)利用三氟甲磺酰氯、三氟甲磺酸钠、TMSCF3和Umemoto’s试剂进行烯胺三氟甲基化。
但以上方法均只适用于末端烯胺和环状烯胺的三氟甲基化反应。而且,使用上述方法进行三氟甲基化反应需要使用到昂贵的光催化剂、过氧化物、特殊的试剂或乙腈等有毒溶剂。上述方法还存在原料范围比较单一,不易得,反应过程中使用大量的金属催化剂等缺点。据此可推断,以上方法底物适用范围窄,操作技术要求高,反应规模不能太大。因此开发反应条件温和、适用范围广泛、符合绿色化学要求的合成方法非常重要。
发明内容
为解决上述技术问题,本发明的目的是提供一种β-三氟甲基烯胺衍生物及其制备方法,本发明提供了一种新的化合物,且该化合物的制备方法具有原料来源简单、反应条件温和、普适性好、产率高的优点。
本发明提供了一种β-三氟甲基烯胺衍生物,其结构通式如下:
其中,R1、R2、R3、R4、R5、R6、R7、R8、R9、R10独立地选自氢、烷基、烷氧基、卤素或三氟甲基。优选地,烷基为甲基;烷氧基为甲氧基。
进一步地,R1、R2、R4、R5、R6、R7、R8、R9、R10为氢,R3为氢、甲基、甲氧基、卤素或三氟甲基;
或R2、R3、R4、R5、R6、R7、R8、R9、R10为氢,R1为卤素;
或R1、R3、R4、R5、R6、R7、R8、R9、R10为氢,R2为卤素;
或R1、R2、R3、R4、R5、R6、R7、R9、R10为氢,R8为氢、甲基、甲氧基或卤素;
或R1、R2、R3、R4、R5、R7、R8、R9、R10为氢,R6为氢、甲基、甲氧基或卤素;
或R1、R2、R3、R4、R5、R6、R8、R9、R10为氢,R7为氢、甲基或卤素。
本发明还提供了一种上述β-三氟甲基烯胺衍生物的制备方法,包括以下步骤:
将取代N-(2-苯基-1-乙烯基)苯甲酰胺衍生物和tongi试剂在碱、含氮配体和铜盐催化剂的作用下在有机溶剂中于80-100℃下反应,得到所述β-三氟甲基烯胺衍生物,其中,取代 N-(2-苯基-1-乙烯基)苯甲酰胺衍生物的结构式如下:
其中,R1、R2、R3、R4、R5、R6、R7、R8、R9、R10独立地选自氢、烷基、烷氧基、卤素或三氟甲基。优选地,烷基为甲基;烷氧基为甲氧基。
进一步地,R1、R2、R4、R5、R6、R7、R8、R9、R10为氢,R3为氢、甲基、甲氧基、卤素或三氟甲基;
或R2、R3、R4、R5、R6、R7、R8、R9、R10为氢,R1为卤素;
或R1、R3、R4、R5、R6、R7、R8、R9、R10为氢,R2为卤素;
或R1、R2、R3、R4、R5、R6、R7、R9、R10为氢,R8为氢、甲基、甲氧基或卤素;
或R1、R2、R3、R4、R5、R7、R8、R9、R10为氢,R6为氢、甲基、甲氧基或卤素;
或R1、R2、R3、R4、R5、R6、R8、R9、R10为氢,R7为氢、甲基或卤素。
进一步地,碱为磷酸氢二钠、碳酸钾、乙酸钠和叔丁醇钾中的一种或几种。优选地,碱为磷酸氢二钠。本发明中,碱的选择对反应的产率的提高起到主要作用,碱性条件下烯胺类化合物的双键比较稳定,有利于提高产率;另外在此条件下碱的存在有利于三氟甲基自由基对双键的进攻,最后有利于氢质子的释放。
进一步地,含氮配体为二甲基乙二胺、四甲基乙二胺和1,10-菲啰啉中的一种或几种。优选地,含氮配体为二甲基乙二胺(DMEDA)DMEDA对本发明的自由基反应有较大的促进作用。含氮配体与铜盐催化剂间可形成配位作用,从而稳定自由基,提高了铜盐催化剂的效率,使得以上反应的产率进一步提升。
进一步地,铜盐催化剂为氯化亚铜、溴化亚铜和碘化亚铜中的一种或几种。优选地,铜盐催化剂为碘化亚铜(CuI)。
本发明使用的togni试剂是一种三氟甲基试剂,结构式如下:
进一步地,取代N-(2-苯基-1-乙烯基)苯甲酰胺衍生物、togni试剂、铜盐催化剂、碱和含氮配体的摩尔比为1:1-2:0.05-0.5:1-3:0.1-1。优选地,取代N-(2-苯基-1-乙烯基)苯甲酰胺衍生物、togni试剂、铜盐催化剂、碱和含氮配体的摩尔比为1:2:0.1:2:0.2。
进一步地,有机溶剂为1,2-二氯乙烷、甲苯、乙腈和1,4-二氧六环中的一种或几种。优选地,有机溶剂为1,2-二氯乙烷(DCE)。
优选地,反应温度为90℃。
进一步地,反应结束后还包括对产物进行柱层析分离提纯处理的步骤。
以上制备方法的反应路线如下:
其中,上式中的R1、R2、R3、R4、R5、R6、R7、R8、R9、R10独立地选自氢、甲基、甲氧基、卤素或三氟甲基。
借由上述方案,本发明至少具有以下优点:
1、本发明使用取代烯胺衍生物为起始物,原料易得、种类多样;本发明首次将Togni 试剂用于非末端取代烯胺衍生物的三氟甲基化反应,由于选用了合适的铜盐催化剂和溶剂,可以使这类自由基反应高效的进行。
2、利用本发明的方法得到的产物类型多样,既可以直接使用,又可以用于其他进一步的反应。
3、本发明反应条件温和、反应操作和后处理过程简单,产率较高,适合于规模生产。
上述说明仅是本发明技术方案的概述,为了能够更清楚了解本发明的技术手段,并可依照说明书的内容予以实施,以下以本发明的较佳实施例并配合详细说明如后。
具体实施方式
下面结合实施例,对本发明的具体实施方式作进一步详细描述。以下实施例用于说明本发明,但不用来限制本发明的范围。
实施例1N-(3,3,3-三氟-2-苯基-1-丙烯基)苯甲酰胺(2a)的合成
以磷酸氢二钠作为碱,以不添加含氮配体(反应(1)-(3))作为添加含氮配体(反应(4)-(6))的对照实验,具体如下:
(1)称取N-(2-苯基-1-乙烯基)苯甲酰胺1a(0.059g,0.25mmol),Togni试剂(0.119g, 0.375mmol),氯化亚铜(0.003g,0.025mmol)溶于4mL 1,2-二氯乙烷(DCE)中,磷酸氢二钠(0.071g,0.5mmol)。混合物加热到90℃,TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(正己烷:丙酮=5:1)提纯后得到化合物2a。分离产率为52%。
(2)称取N-(2-苯基-1-乙烯基)苯甲酰胺1a(0.059g,0.25mmol),Togni试剂(0.119g, 0.375mmol),溴化亚铜(0.004g,0.025mmol)溶于4mL 1,2-二氯乙烷(DCE)中,磷酸氢二钠(0.071g,0.5mmol)。混合物加热到90℃,TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(正己烷:丙酮=5:1)提纯后得到化合物2a。分离产率为55%。
(3)称取N-(2-苯基-1-乙烯基)苯甲酰胺1a(0.059g,0.25mmol),Togni试剂(0.119g, 0.375mmol),碘化亚铜(0.005g,0.025mmol)溶于4mL 1,2-二氯乙烷(DCE)中,磷酸氢二钠(0.071g,0.5mmol)。混合物加热到90℃,TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(正己烷:丙酮=5:1)提纯后得到化合物2a。分离产率为56%。
(4)称取N-(2-苯基-1-乙烯基)苯甲酰胺1a(0.059g,0.25mmol),Togni试剂(0.119g, 0.375mmol),碘化亚铜(0.005g,0.025mmol)溶于4mL 1,2-二氯乙烷(DCE)中,磷酸氢二钠(0.071g,0.5mmol),DMEDA(0.005g,0.05mmol)。混合物加热到90℃,TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(正己烷:丙酮=5:1)提纯后得到化合物2a。分离产率为68%。
(5)称取N-(2-苯基-1-乙烯基)苯甲酰胺1a(0.059g,0.25mmol),Togni试剂(0.119g, 0.375mmol),碘化亚铜(0.005g,0.025mmol)溶于4mL 1,2-二氯乙烷(DCE)中,磷酸氢二钠(0.071g,0.5mmol),四甲基乙二胺(0.006g,0.05mmol)。混合物加热到90℃,TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(正己烷:丙酮=5:1)提纯后得到化合物2a。分离产率为41%。
(6)称取N-(2-苯基-1-乙烯基)苯甲酰胺1a(0.059g,0.25mmol),Togni试剂(0.119g, 0.375mmol),碘化亚铜(0.005g,0.025mmol)溶于4mL 1,2-二氯乙烷(DCE)中,磷酸氢二钠(0.071g,0.5mmol),1,10-菲洛林(0.009g,0.05mmol)。混合物加热到90℃,TLC 跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(正己烷:丙酮=5:1) 提纯后得到化合物2a。分离产率为56%。
以其他试剂作为碱,以不添加含氮配体(反应(7)-(9))作为对照实验,具体如下:
(7)称取N-(2-苯基-1-乙烯基)苯甲酰胺1a(0.059g,0.25mmol),Togni试剂(0.119g, 0.375mmol),碘化亚铜(0.005g,0.025mmol)溶于4mL 1,2-二氯乙烷(DCE)中,碳酸钾 (0.064g,0.5mmol)。混合物加热到90℃,TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(正己烷:丙酮=5:1)提纯后得到化合物2a。分离产率为47%。
(8)称取N-(2-苯基-1-乙烯基)苯甲酰胺1a(0.059g,0.25mmol),Togni试剂(0.119g, 0.375mmol),碘化亚铜(0.005g,0.025mmol)溶于4mL 1,2-二氯乙烷(DCE)中,乙酸钠 (0.041g,0.5mmol)。混合物加热到90℃,TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(正己烷:丙酮=5:1)提纯后得到化合物2a。分离产率为54%。
(9)称取N-(2-苯基-1-乙烯基)苯甲酰胺1a(0.059g,0.25mmol),Togni试剂(0.119g, 0.375mmol),碘化亚铜(0.005g,0.025mmol)溶于4mL 1,2-二氯乙烷(DCE)中,叔丁醇钾(0.056g,0.5mmol)。混合物加热到90℃,TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(正己烷:丙酮=5:1)提纯后得到化合物2a。分离产率为47%。
以不添加含氮配体和碱(反应(10)-(12)),作为本发明的对照实验,具体如下:
(10)称取N-(2-苯基-1-乙烯基)苯甲酰胺1a(0.059g,0.25mmol),Togni试剂(0.119g, 0.375mmol),碘化亚铜(0.005g,0.025mmol)溶于4mL 1,4-二氧六环中,混合物加热到90℃, TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(正己烷:丙酮=5:1) 提纯后得到化合物2a。分离产率为17%。
(11)称取N-(2-苯基-1-乙烯基)苯甲酰胺1a(0.059g,0.25mmol),Togni试剂(0.119g, 0.375mmol),碘化亚铜(0.005g,0.025mmol)溶于4mL甲苯中,混合物加热到90℃,TLC 跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(正己烷:丙酮=5:1) 提纯后得到化合物2a。分离产率为6%。
(12)称取N-(2-苯基-1-乙烯基)苯甲酰胺1a(0.059g,0.25mmol),Togni试剂(0.119g, 0.375mmol),碘化亚铜(0.005g,0.025mmol)溶于4mL乙腈中,混合物加热到90℃,TLC 跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(正己烷:丙酮=5:1) 提纯后得到化合物2a。分离产率为9%。
改变反应温度,(反应(13)),作为本发明的对照实验,具体如下:
(13)称取N-(2-苯基-1-乙烯基)苯甲酰胺1a(0.059g,0.25mmol),Togni试剂(0.119g, 0.375mmol),碘化亚铜(0.005g,0.025mmol)溶于4mL 1,2-二氯乙烷(DCE)中,磷酸氢二钠(0.071g,0.5mmol),DMEDA(0.005g,0.05mmol)。混合物加热到60℃,TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(正己烷:丙酮=5:1)提纯后得到化合物2a。分离产率为26%。
(14)称取N-(2-苯基-1-乙烯基)苯甲酰胺1a(0.059g,0.25mmol),Togni试剂(0.119g, 0.375mmol),碘化亚铜(0.005g,0.025mmol)溶于4mL 1,2-二氯乙烷(DCE)中,磷酸氢二钠(0.071g,0.5mmol),DMEDA(0.005g,0.05mmol)。混合物加热到100℃,TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(正己烷:丙酮=5:1)提纯后得到呈白色粉末状的化合物2a。分离产率为66%。
以上实验均得到化合物2a,其核磁和HRMS测试结果如下:
2a:1H NMR(400MHz,CDCl3)δ:7.95(d,J=11.4Hz,1H),7.80(d,J=8.7Hz,1H),7.61(d,J=7.3Hz,2H),7.58–7.47(m,4H),7.47–7.37(m,4H);13C NMR(101MHz,CDCl3)δ: 164.28(s),132.81(s),132.32(s),130.01(s),129.65(s),129.58(s),129.42(s),128.96(s),127.16 (s),126.59(q,J=6.06Hz),124.07(q,J=271.69Hz),112.73(q,J=31.31Hz);19FNMR(376 MHz,CDCl3)δ:-63.35(s).HRMS(ESI-TOF)calcd for C16H12F3NNaO(M+Na)+:314.0769,found 314.0647。
实施例2 4-甲基-N-(3,3,3-三氟-2-苯基-1-丙烯基)苯甲酰胺(2b)的
称取4-甲基-N-(2-苯基-1-乙烯基)苯甲酰胺1b(0.060g,0.25mmol),Togni试剂(0.119g, 0.375mmol),碘化亚铜(0.005g,0.025mmol)溶于4mL 1,2-二氯乙烷(DCE)中,磷酸氢二钠(0.071g,0.5mmol),DMEDA(0.005g,0.05mmol)。混合物加热到90℃,TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(正己烷:丙酮=5:1)提纯后得到化合物2b。分离产率为68%。
2b:68%产率;1H NMR(400MHz,CDCl3)δ:7.94(d,J=10.4Hz,1H),7.77(d,J=10.1Hz,1H),7.55–7.46(m,5H),7.40(d,J=6.9Hz,2H),7.22(d,J=8.0Hz,2H),2.38(s,3H);13CNMR(101MHz,CDCl3)δ:164.24(s),143.65(s),130.10(s),129.62(s),129.59(s),129.46(s), 129.37(s),128.89(s),127.20(s),126.73(q,J=7.07Hz),124.19(q,J=270.7Hz),112.51(q,J= 31.6Hz),21.52(s);19F NMR(376MHz,CDCl3)δ:-63.27(s).HRMS(ESI-TOF)calcd for C17H14F3NNaO(M+Na)+:328.0925,found 328.0920。
实施例3 4-甲氧基-N-(3,3,3-三氟-2-苯基-1-丙烯基)苯甲酰胺(2c)的合成
称取4-甲氧基-N-(2-苯基-1-乙烯基)苯甲酰胺1c(0.063g,0.25mmol),Togni试剂(0.119g, 0.375mmol),碘化亚铜(0.005g,0.025mmol)溶于4mL 1,2-二氯乙烷(DCE)中,磷酸氢二钠(0.071g,0.5mmol),DMEDA(0.005g,0.05mmol)。混合物加热到90℃,TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(正己烷:丙酮=5:1)提纯后得到化合物2c。分离产率为61%。
2c:61%产率;1H NMR(400MHz,CDCl3)δ:7.96–7.83(m,1H),7.74(d,J=11.3Hz,1H),7.56(t,J=7.9Hz,2H),7.53–7.43(m,3H),7.40(d,J=7.1Hz,2H),6.89(d,J=8.7Hz,2H),3.82(s,3H);13C NMR(101MHz,CDCl3)δ:163.68(s),163.23(s),130.18(s),129.62(s),129.33(s),129.19(s),126.83(q,J=7.0Hz),124.39(s),124.21(q,J=270.6Hz),114.17(s), 112.18(q,J=31.7Hz),55.50(s);19F NMR(376MHz,CDCl3)δ:-63.17(s).HRMS(ESI-TOF) calcd for C17H14F3NNaO2(M+Na)+:344.0874,found 344.0871。
实施例4 2-羟基-N-(3,3,3-三氟-2-苯基-1-丙烯基)苯甲酰胺(2d)的合成
称取2-羟基-N-(2-苯基-1-乙烯基)苯甲酰胺1d(0.060g,0.25mmol),Togni试剂(0.119g, 0.375mmol),碘化亚铜(0.005g,0.025mmol)溶于4mL 1,2-二氯乙烷(DCE)中,磷酸氢二钠(0.071g,0.5mmol),DMEDA(0.005g,0.05mmol)。混合物加热到90℃,TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(正己烷:丙酮=5:1)提纯后得到化合物2d。分离产率为71%。
2d:71%产率;1H NMR(400MHz,CDCl3)δ:11.42(s,1H),7.99(d,J=11.0Hz,1H),7.90 (d,J=11.4Hz,1H),7.57–7.46(m,3H),7.41(t,J=7.0Hz,3H),6.96(dd,J=17.3,8.2Hz,2H), 6.79(t,J=7.6Hz,1H);13C NMR(101MHz,CDCl3)δ:166.56(s),161.50(s),135.12(s),129.27 (s),129.18(s),129.06(s),124.92(s),124.92(q,J=7.1Hz),123.42(q,J=270.8Hz),118.83(s), 118.52(s),113.58(q,J=31.8Hz),112.49(s);19F NMR(376MHz,CDCl3)δ:--63.54(s).HRMS (ESI-TOF)calcd for C16H12F3NNaO2(M+Na)+:330.0718,found 330.0723。
实施例5 2-氯-N-(3,3,3-三氟-2-苯基-1-丙烯基)苯甲酰胺(2e)的合成
称取2-氯-N-(2-苯基-1-乙烯基)苯甲酰胺1e(0.065g,0.25mmol),Togni试剂(0.119g, 0.375mmol),碘化亚铜(0.005g,0.025mmol)溶于4mL 1,2-二氯乙烷(DCE)中,磷酸氢二钠(0.071g,0.5mmol),DMEDA(0.005g,0.05mmol)。混合物加热到90℃,TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(正己烷:丙酮=5:1)提纯后得到化合物2e。分离产率为70%。
2e:70%产率;1H NMR(400MHz,CDCl3)δ:7.91(d,J=11.6Hz,1H),7.76(d,J=11.3Hz,1H),7.49(ddd,J=27.7,13.3,7.0Hz,5H),6.81(s,2H),3.88(s,3H),3.83(s,6H);13CNMR (101MHz,CDCl3)δ:163.29(s),152.86(s),141.57(s),129.67(s),129.18(s),129.06(s),128.93 (s),127.01(s),126.19(q,J=6.9Hz),123.57(q,J=270.6Hz),112.38(q,J=31.9Hz),104.02(s), 60.45(s),55.70(s);19F NMR(376MHz,CDCl3)δ:--63.30(s).HRMS(ESI-TOF)calcd for C19H18F3NNaO4(M+Na)+:404.1086,found 404.1075。
实施例6 3-溴-N-(3,3,3-三氟-2-苯基-1-丙烯基)苯甲酰胺(2f)的合成
称取3-溴-N-(2-苯基-1-乙烯基)苯甲酰胺1f(0.075g,0.25mmol),Togni试剂(0.119g, 0.375mmol),碘化亚铜(0.005g,0.025mmol)溶于4mL 1,2-二氯乙烷(DCE)中,磷酸氢二钠(0.071g,0.5mmol),DMEDA(0.005g,0.05mmol)。混合物加热到90℃,TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(正己烷:丙酮=5:1)提纯后得到化合物2f。分离产率为63%。
2f:63%产率;1H NMR(400MHz,CDCl3)δ:7.90(d,J=12.2Hz,1H),7.81(t,J=1.7Hz, 1H),7.74(d,J=10.8Hz,1H),7.68–7.61(m,1H),7.57–7.47(m,3H),7.41(dd,J=15.8,7.4 Hz,3H),7.31–7.23(m,1H);13C NMR(101MHz,CDCl3)δ:162.48(s),135.27(s),133.77(s), 130.28(s),129.92(s),129.30(s),129.23(s),129.11(s),129.05(s),125.83(q,J=6.8Hz),124.81 (s),123.62(q,J=270.5Hz),122.76(s),113.17(q,J=31.6Hz);19FNMR(376MHz,CDCl3)δ: -63.46(s).HRMS(ESI-TOF)calcd for C16H11BrF3NNaO(M+Na)+:391.9874,found 391.9889。
实施例7 4-溴-N-(3,3,3-三氟-2-苯基-1-丙烯基)苯甲酰胺(2g)的合成
称取4-溴-N-(2-苯基-1-乙烯基)苯甲酰胺1g(0.075g,0.25mmol),Togni试剂(0.119g, 0.375mmol),碘化亚铜(0.005g,0.025mmol)溶于4mL 1,2-二氯乙烷(DCE)中,磷酸氢二钠(0.071g,0.5mmol),DMEDA(0.005g,0.05mmol)。混合物加热到90℃,TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(正己烷:丙酮=5:1)提纯后得到化合物2g。分离产率为65%。
2g:65%产率;1H NMR(400MHz,CDCl3)δ:7.90(d,J=11.5Hz,1H),7.79–7.71(m,1H),7.59–7.43(m,7H),7.39(d,J=6.9Hz,2H);13C NMR(101MHz,CDCl3)δ:163.42(s),138.21(s),132.24(s),131.12(s),129.85(s),129.70(s),129.54(s),128.69(s),127.77(s),126.39 (q,J=6.1Hz),124.01(q,J=271.7Hz),113.39(q,J=31.9Hz);19F NMR(376MHz,CDCl3)δ: --63.44(s).HRMS(ESI-TOF)calcd for C16H12F3NNaO(M+Na)+:C16H11BrF3NNaO(M+Na)+: 391.9874,found 391.9867。
实施例8 4-三氟甲基-N-(3,3,3-三氟-2-苯基-1-丙烯基)苯甲酰胺(2h)的合成
称取4-三氟甲基-N-(2-苯基-1-乙烯基)苯甲酰胺1h(0.073g,0.25mmol),Togni试剂 (0.119g,0.375mmol),碘化亚铜(0.005g,0.025mmol)溶于4mL 1,2-二氯乙烷(DCE) 中,磷酸氢二钠(0.071g,0.5mmol),DMEDA(0.005g,0.05mmol)。混合物加热到90℃, TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(正己烷:丙酮=5:1) 提纯后得到化合物2h。分离产率为57%。
2h:57%产率;1H NMR(400MHz,CDCl3)δ:7.91(d,J=11.3Hz,1H),7.86–7.77(m,1H),7.69(q,J=8.6Hz,4H),7.59–7.44(m,3H),7.40(d,J=6.7Hz,2H);13C NMR(101MHz,CDCl3)δ:162.62(s),135.10(s),133.88(q,J=33.3Hz),129.26(s),129.16(s),129.03(s),127.17 (s),125.75(q,J=7.1),125.54(q,J=4.0Hz),123.43(q,J=270.9Hz),122.87(q,J=272.7Hz), 113.51(q,J=31.3Hz);19F NMR(376MHz,CDCl3)δ:--63.24(s).HRMS(ESI-TOF)calcd for C17H11F6NNaO(M+Na)+:382.0643,found 382.0629。
实施例9N-(3,3,3-三氟-2-(4-甲基苯基)-1-丙烯基)苯甲酰胺(2i)的合成
称取N-(2-(4-甲基苯基)-1-乙烯基)苯甲酰胺1i(0.060g,0.25mmol),Togni试剂(0.119g, 0.375mmol),碘化亚铜(0.005g,0.025mmol)溶于4mL 1,2-二氯乙烷(DCE)中,磷酸氢二钠(0.071g,0.5mmol),DMEDA(0.005g,0.05mmol)。混合物加热到90℃,TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(正己烷:丙酮=5:1)提纯后得到化合物2i。分离产率为73%。
2i:73%产率;1H NMR(400MHz,CDCl3)δ:7.92(d,J=11.6Hz,1H),7.81(dd,J=9.3,4.7Hz,1H),7.62(dd,J=5.2,3.3Hz,2H),7.57–7.51(m,1H),7.42(dd,J=10.5,4.7Hz,2H),7.30(q,J=8.1Hz,4H),2.42(s,3H);13C NMR(101MHz,CDCl3)δ:164.30(s),139.42(s),132.75(s),132.40(s),130.34(s),129.37(s),128.93(s),127.17(s),126.91(s),126.39(q,J=13.8, 6.9Hz),124.15(q,J=270.8Hz),112.92(q,J=31.8Hz),21.35(s);19F NMR(376MHz,CDCl3) δ:-63.46(s).HRMS(ESI-TOF)calcd for C17H14F3NNaO(M+Na)+:328.0925,found 328.0932。
实施例10N-(3,3,3-三氟-2-(4-甲氧基苯基)-1-丙烯基)苯甲酰胺(2j)的合成
称取N-(2-(4-甲氧基苯基)-1-乙烯基)苯甲酰胺1j(0.063g,0.25mmol),Togni试剂(0.119g, 0.375mmol),碘化亚铜(0.005g,0.025mmol)溶于4mL 1,2-二氯乙烷(DCE)中,磷酸氢二钠(0.071g,0.5mmol),DMEDA(0.005g,0.05mmol)。混合物加热到90℃,TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(正己烷:丙酮=5:1)提纯后得到化合物2j。分离产率为55%。。
2j:55%产率;1H NMR(400MHz,CDCl3)δ:7.91(d,J=11.4Hz,1H),7.79(d,J=11.0Hz,1H),7.66–7.60(m,2H),7.54(t,J=7.4Hz,1H),7.43(t,J=7.7Hz,2H),7.32(d,J=8.6Hz, 2H),7.04(dd,J=6.7,4.8Hz,2H),3.87(s,3H);13C NMR(101MHz,CDCl3)δ:164.28(s), 160.24(s),132.76(s),132.38(s),130.92(s),128.95(s),127.16(s),126.46(q,J=7.0Hz),124.16 (q,J=270.6Hz),121.80(s),115.06(s),112.65(q,J=31.8Hz),55.36(s);19F NMR(376MHz, CDCl3)δ:63.70(s).HRMS(ESI-TOF)calcd for C17H14F3NNaO2(M+Na)+:344.0874,found 344.0876。
实施例11N-(3,3,3-三氟-2-(2-甲基苯基)-1-丙烯基)苯甲酰胺(2k)的合成
称取N-(2-(2-甲基苯基)-1-乙烯基)苯甲酰胺1k(0.060g,0.25mmol),Togni试剂(0.119g, 0.375mmol),碘化亚铜(0.005g,0.025mmol)溶于4mL 1,2-二氯乙烷(DCE)中,磷酸氢二钠(0.071g,0.5mmol),DMEDA(0.005g,0.05mmol)。混合物加热到90℃,TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(正己烷:丙酮=5:1)提纯后得到化合物2k。分离产率为73%。
2k:73%产率;1H NMR(400MHz,CDCl3)δ:7.95(d,J=11.5Hz,1H),7.60–7.51(m,3H),7.45–7.37(m,4H),7.33(ddd,J=8.6,7.9,3.6Hz,2H),7.26(d,J=6.4Hz,1H),2.31(s,3H);13C NMR(101MHz,CDCl3)δ:163.81(s),137.59(s),132.33(s),131.84(s),130.54(s),130.42(s),129.39(s),128.47(s),127.96(s),126.64(s),126.40(q,J=6.8Hz),123.69(q,J= 270.6Hz),111.64(q,J=32.3Hz),18.88(s).;19F NMR(376MHz,CDCl3)δ:--63.99(s).HRMS (ESI-TOF)calcd for C17H14F3NNaO(M+Na)+:328.0925,found 328.0937。
实施例12N-(3,3,3-三氟-2-(2-甲基苯基)-1-丙烯基)苯甲酰胺(2l)的合成
称取N-(2-(2-甲氧基苯基)-1-乙烯基)苯甲酰胺1l(0.063g,0.25mmol),Togni试剂(0.119g, 0.375mmol),碘化亚铜(0.005g,0.025mmol)溶于4mL 1,2-二氯乙烷(DCE)中,磷酸氢二钠(0.071g,0.5mmol),DMEDA(0.005g,0.05mmol)。混合物加热到90℃,TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(正己烷:丙酮=5:1)提纯后得到化合物2l。分离产率为67%。
2l:67%产率;1H NMR(400MHz,CDCl3)δ:7.93(d,J=11.0Hz,1H),7.71(dd,J=5.6,4.2Hz,1H),7.62(dd,J=5.2,3.3Hz,2H),7.56–7.51(m,1H),7.47–7.40(m,3H),7.34(d,J=7.2Hz,1H),7.09(dd,J=7.7,6.2Hz,2H),3.87(s,3H);13C NMR(101MHz,CDCl3)δ:164.35(s),157.09(s),132.67(s),131.50(s),131.13(s),128.91(s),127.52(q,J=7.1Hz),127.12(s), 124.30(q,J=271.7Hz),121.58(s),118.24(s),112.19(s),108.99(q,J=32.1Hz),56.15(s);19F NMR(376MHz,CDCl3)δ:-62.53(s).HRMS(ESI-TOF)calcd forC17H14F3NNaO2(M+Na)+: 344.0874,found 344.0878。
实施例13N-(3,3,3-三氟-2-(3-甲基苯基)-1-丙烯基)苯甲酰胺(2m)的合成
称取N-(2-(3-甲基苯基)-1-乙烯基)苯甲酰胺1m(0.060g,0.25mmol),Togni试剂(0.119g, 0.375mmol),碘化亚铜(0.005g,0.025mmol)溶于4mL 1,2-二氯乙烷(DCE)中,磷酸氢二钠(0.071g,0.5mmol),DMEDA(0.005g,0.05mmol)。混合物加热到90℃,TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(正己烷:丙酮=5:1)提纯后得到化合物2m。分离产率为68%。
2m:68%产率;1H NMR(400MHz,CDCl3)δ:7.93(d,J=11.2Hz,1H),7.81(d,J=10.7Hz,1H),7.62(t,J=7.3Hz,2H),7.54(t,J=7.4Hz,1H),7.42(dd,J=15.1,7.6Hz,3H),7.28(d, J=7.7Hz,1H),7.19(d,J=11.1Hz,2H),2.42(s,3H);13C NMR(101MHz,CDCl3)δ:163.78(s), 139.06(s),132.29(s),131.91(s),129.71(s),129.62(s),129.42(s),128.99(s),128.47(s),126.69 (s),126.06(s),125.97(q,J=7.1Hz),123.64(q,J=270.8Hz),112.59(q,J=32.3Hz),20.99(s);19F NMR(376MHz,CDCl3)δ:-63.35(s).HRMS(ESI-TOF)calcd forC17H14F3NNaO(M+Na)+: 328.0925,found 328.0912。
实施例14N-(3,3,3-三氟-2-(4-氟苯基)-1-丙烯基)苯甲酰胺(2n)的合成
称取N-(2-(4-氟苯基)-1-乙烯基)苯甲酰胺1n(0.061g,0.25mmol),Togni试剂(0.119g, 0.375mmol),碘化亚铜(0.005g,0.025mmol)溶于4mL 1,2-二氯乙烷(DCE)中,磷酸氢二钠(0.071g,0.5mmol),DMEDA(0.005g,0.05mmol)。混合物加热到90℃,TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(正己烷:丙酮=5:1)提纯后得到化合物2n。分离产率为65%。
2n:65%产率;1H NMR(400MHz,CDCl3)δ:7.94(d,J=10.8Hz,1H),7.72(d,J=10.5Hz,1H),7.65–7.58(m,2H),7.55(t,J=7.4Hz,1H),7.44(d,J=7.8Hz,2H),7.42–7.36(m,2H),7.25–7.14(m,2H);13C NMR(101MHz,CDCl3)δ:163.81(s),162.70(d,J=250.0Hz),132.45(s),131.71(s),131.23(d,J=8.3Hz),128.53(s),126.68(s),126.54(q,J=7.0Hz),125.34 (d,J=3.3Hz),123.49(q,J=270.5Hz),116.37(d,J=21.7Hz),111.32(q,J=31.9Hz);19F NMR(376MHz,CDCl3)δ:-63.63(s),-110.99(s).HRMS(ESI-TOF)calcd forC16H11F4NNaO (M+Na)+:332.0674,found 332.0676。
实施例15N-(3,3,3-三氟-2-(4-氯苯基)-1-丙烯基)苯甲酰胺(2o)的合成
称取N-(2-(4-氯苯基)-1-乙烯基)苯甲酰胺1o(0.065g,0.25mmol),Togni试剂(0.119g, 0.375mmol),碘化亚铜(0.005g,0.025mmol)溶于4mL 1,2-二氯乙烷(DCE)中,磷酸氢二钠(0.071g,0.5mmol),DMEDA(0.005g,0.05mmol)。混合物加热到90℃,TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(正己烷:丙酮=5:1)提纯后得到化合物2o。分离产率为63%。
2o:63%产率;1H NMR(400MHz,CDCl3)δ:7.94(d,J=11.6Hz,1H),7.76(d,J=11.5Hz,1H),7.65–7.59(m,2H),7.56(dd,J=10.6,4.3Hz,1H),7.52–7.47(m,2H),7.44(t,J=7.6 Hz,2H),7.34(d,J=8.3Hz,2H);13C NMR(101MHz,CDCl3)δ:163.83(s),135.15(s),132.49 (s),131.64(s),130.57(s),129.50(s),128.54(s),127.92(s),126.72(s),126.59(q,J=6.9Hz), 123.44(q,J=270.8Hz),111.10(q,J=31.9Hz);19F NMR(376MHz,CDCl3)δ:-63.33(s). HRMS(ESI-TOF)calcd for C16H11ClF3NNaO(M+Na)+:348.0379,found348.0371。
实施例16N-(3,3,3-三氟-2-(4-溴苯基)-1-丙烯基)苯甲酰胺(2p)的合成
称取N-(2-(4-溴苯基)-1-乙烯基)苯甲酰胺1p(0.075g,0.25mmol),Togni试剂(0.119g, 0.375mmol),碘化亚铜(0.005g,0.025mmol)溶于4mL 1,2-二氯乙烷(DCE)中,磷酸氢二钠(0.071g,0.5mmol),DMEDA(0.005g,0.05mmol)。混合物加热到90℃,TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(正己烷:丙酮=5:1)提纯后得到化合物2p。分离产率为66%。
2p:66%产率;1H NMR(400MHz,CDCl3)δ:7.94(d,J=11.6Hz,1H),7.74(d,J=11.2Hz,1H),7.64(dd,J=12.1,7.9Hz,4H),7.56(t,J=7.4Hz,1H),7.44(t,J=7.7Hz,2H),7.35– 7.23(m,2H);13C NMR(101MHz,CDCl3)δ:163.82(s),132.51(s),132.47(s),131.63(s),130.81 (s),128.56(s),128.42(s),126.72(s),126.59(q,J=7.1Hz),123.38(s),123.37(q,J=270.8Hz), 111.11(q,J=31.9Hz);19F NMR(376MHz,CDCl3)δ:-63.29(s).HRMS(ESI-TOF)calcd for C16H11BrF3NNaO(M+Na)+:391.9874,found 391.9861。
实施例17N-(3,3,3-三氟-2-(2-氟苯基)-1-丙烯基)苯甲酰胺(2q)的合成
称取N-(2-(2-氟苯基)-1-乙烯基)苯甲酰胺1q(0.061g,0.25mmol),Togni试剂(0.119g, 0.375mmol),碘化亚铜(0.005g,0.025mmol)溶于4mL 1,2-二氯乙烷(DCE)中,磷酸氢二钠(0.071g,0.5mmol),DMEDA(0.005g,0.05mmol)。混合物加热到90℃,TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(正己烷:丙酮=5:1)提纯后得到化合物2q。分离产率为60%。
2q:60%产率;1H NMR(400MHz,CDCl3)δ:8.59–8.41(m,1H),8.12(td,J=7.9,1.7Hz,1H),8.01–7.92(m,1H),7.57–7.45(m,4H),7.39(d,J=6.8Hz,2H),7.27(dd,J=10.6,4.3 Hz,1H),7.03(dd,J=12.4,8.4Hz,1H);13C NMR(101MHz,CDCl3)δ:160.33(d,J=3.3Hz), 160.27(d,J=248.3Hz),134.30(d,J=9.7Hz),131.98(d,J=1.3Hz),129.47(s),129.06(s), 128.96(s),128.86(s),125.94(q,J=7.0Hz),124.74(d,J=3.2Hz),123.65(q,J=270.7Hz), 118.62(d,J=10.4Hz),115.74(d,J=24.7Hz),113.07(q,J=31.6Hz);19F NMR(376MHz, CDCl3)δ:-63.34(s).HRMS(ESI-TOF)calcd for C16H11F4NNaO(M+Na)+:332.0674,found 332.0669。
实施例18N-(3,3,3-三氟-2-(2-氯苯基)-1-丙烯基)苯甲酰胺(2r)的合成
称取N-(2-(2-氯苯基)-1-乙烯基)苯甲酰胺1r(0.065g,0.25mmol),Togni试剂(0.119g, 0.375mmol),碘化亚铜(0.005g,0.025mmol)溶于4mL 1,2-二氯乙烷(DCE)中,磷酸氢二钠(0.071g,0.5mmol),DMEDA(0.005g,0.05mmol)。混合物加热到90℃,TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(正己烷:丙酮=5:1)提纯后得到化合物2r。分离产率为67%。
2r:67%产率;1H NMR(400MHz,CDCl3)δ:7.99(d,J=10.8Hz,1H),7.64–7.58(m,3H),7.54(t,J=7.4Hz,1H),7.43(dt,J=16.5,4.5Hz,6H);13C NMR(101MHz,CDCl3)δ:164.03(s),134.28(s),132.40(s),131.96(s),131.91(s),130.70(s),129.98(s),128.48(s),128.30 (s),127.62(q,J=6.6Hz),127.28(s),126.77(s),123.44(q,J=271.9Hz),108.95(q,J=32.7 Hz);19F NMR(376MHz,CDCl3)δ:-63.48(s).HRMS(ESI-TOF)calcd forC16H11ClF3NNaO (M+Na)+:348.0379,found 348.0375。
实施例19N-(3,3,3-三氟-2-(2-溴苯基)-1-丙烯基)苯甲酰胺(2s)的合成
称取N-(2-(2-溴苯基)-1-乙烯基)苯甲酰胺1s(0.075g,0.25mmol),Togni试剂(0.119g, 0.375mmol),碘化亚铜(0.005g,0.025mmol)溶于4mL 1,2-二氯乙烷(DCE)中,磷酸氢二钠(0.071g,0.5mmol),DMEDA(0.005g,0.05mmol)。混合物加热到90℃,TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(正己烷:丙酮=5:1)提纯后得到化合物2s。分离产率为66%。
2s:66%产率;1H NMR(400MHz,CDCl3)δ:7.97(d,J=11.5Hz,1H),7.78(d,J=8.1Hz, 1H),7.63(d,J=7.4Hz,2H),7.53(d,J=7.5Hz,1H),7.41(ddd,J=13.5,6.8,2.5Hz,6H);13C NMR(101MHz,CDCl3)δ:164.06(s),133.28(s),132.41(s),132.07(s),131.92(s),130.84(s), 129.85(s),128.49(s),127.89(s),127.43(q,J=6.5Hz),126.79(s),124.32(s),123.36(q,J= 270.9Hz),110.65(q,J=32.6Hz);19F NMR(376MHz,CDCl3)δ:-63.56(s).HRMS(ESI-TOF) calcd for C16H11BrF3NNaO(M+Na)+:391.9874,found391.9870。
实施例20N-(3,3,3-三氟-2-(3-氯苯基)-1-丙烯基)苯甲酰胺(2t)的合成
称取N-(2-(3-氯苯基)-1-乙烯基)苯甲酰胺1t(0.065g,0.25mmol),Togni试剂(0.119g, 0.375mmol),碘化亚铜(0.005g,0.025mmol)溶于4mL 1,2-二氯乙烷(DCE)中,磷酸氢二钠(0.071g,0.5mmol),DMEDA(0.005g,0.05mmol)。混合物加热到90℃,TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(正己烷:丙酮=5:1)提纯后得到化合物2t。分离产率为60%。
2t:60%产率;1H NMR(400MHz,CDCl3)δ:7.94(d,J=10.5Hz,1H),7.81(d,J=9.2Hz, 1H),7.73–7.34(m,8H),7.28(t,J=6.5Hz,1H);13C NMR(101MHz,CDCl3)δ:163.89(s), 135.12(s),132.52(s),131.62(s),131.30(s),130.44(s),129.27(s),129.21(s),128.54(s),127.36 (s),126.83(q,J=7.1Hz),126.75(s),123.41(q,J=270.8Hz),110.93(q,J=32.3Hz);19F NMR (376MHz,CDCl3)δ:-63.17(d,J=3.6Hz).HRMS(ESI-TOF)calcdfor C16H11ClF3NNaO (M+Na)+:348.0379,found 348.0365。
总之,本发明公开了一种β-三氟甲基烯胺衍生物的制备方法,以取代的N-(2-苯基-1-乙烯基)苯甲酰胺衍生物为底物,以铜盐为催化剂,在有机溶剂中,与tongi试剂、磷酸氢二钠和含氮配体在80-100℃下反应,以较高的收率得到β-三氟甲基烯胺衍生物。
以上所述仅是本发明的优选实施方式,并不用于限制本发明,应当指出,对于本技术领域的普通技术人员来说,在不脱离本发明技术原理的前提下,还可以做出若干改进和变型,这些改进和变型也应视为本发明的保护范围。
Claims (9)
1.一种β-三氟甲基烯胺衍生物,其特征在于,其结构通式如下:
其中,R1、R2、R3、R4、R5、R6、R7、R8、R9、R10独立地选自氢、烷基、烷氧基、卤素或三氟甲基。
2.根据权利要求1所述的β-三氟甲基烯胺衍生物,其特征在于:
R1、R2、R4、R5、R6、R7、R8、R9、R10为氢,R3为氢、烷基、烷氧基、卤素或三氟甲基;
或R2、R3、R4、R5、R6、R7、R8、R9、R10为氢,R1为卤素;
或R1、R3、R4、R5、R6、R7、R8、R9、R10为氢,R2为卤素;
或R1、R2、R3、R4、R5、R6、R7、R9、R10为氢,R8为氢、烷基、烷氧基或卤素;
或R1、R2、R3、R4、R5、R7、R8、R9、R10为氢,R6为氢、烷基、烷氧基或卤素;
或R1、R2、R3、R4、R5、R6、R8、R9、R10为氢,R7为氢、烷基或卤素。
3.根据权利要求1或2所述的β-三氟甲基烯胺衍生物的制备方法,其特征在于,包括以下步骤:
将取代N-(2-苯基-1-乙烯基)苯甲酰胺衍生物和tongi试剂在碱、含氮配体和铜盐催化剂的作用下在有机溶剂中于80-100℃下反应,得到所述β-三氟甲基烯胺衍生物;其中,所述取代N-(2-苯基-1-乙烯基)苯甲酰胺衍生物的结构式如下:
其中,R1、R2、R3、R4、R5、R6、R7、R8、R9、R10独立地选自氢、烷基、烷氧基、卤素或三氟甲基。
4.根据权利要求3所述的制备方法,其特征在于:
R1、R2、R4、R5、R6、R7、R8、R9、R10为氢,R3为氢、烷基、烷氧基、卤素或三氟甲基;
或R2、R3、R4、R5、R6、R7、R8、R9、R10为氢,R1为卤素;
或R1、R3、R4、R5、R6、R7、R8、R9、R10为氢,R2为卤素;
或R1、R2、R3、R4、R5、R6、R7、R9、R10为氢,R8为氢、烷基、烷氧基或卤素;
或R1、R2、R3、R4、R5、R7、R8、R9、R10为氢,R6为氢、烷基、烷氧基或卤素;
或R1、R2、R3、R4、R5、R6、R8、R9、R10为氢,R7为氢、烷基或卤素。
5.根据权利要求3所述的制备方法,其特征在于:所述碱为磷酸氢二钠、碳酸钾、乙酸钠和叔丁醇钾中的一种或几种。
6.根据权利要求3所述的制备方法,其特征在于:所述含氮配体为二甲基乙二胺、四甲基乙二胺和1,10-菲啰啉中的一种或几种。
7.根据权利要求3所述的制备方法,其特征在于:所述铜盐催化剂为氯化亚铜、溴化亚铜和碘化亚铜中的一种或几种。
8.根据权利要求3-7中任一项所述的制备方法,其特征在于:所述取代N-(2-苯基-1-乙烯基)苯甲酰胺衍生物、togni试剂、铜盐催化剂、碱和含氮配体的摩尔比为1:1-2:0.05-0.5:1-3:0.1-1。
9.根据权利要求3所述的制备方法,其特征在于:所述有机溶剂为1,2-二氯乙烷、甲苯、乙腈和1,4-二氧六环中的一种或几种。
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US10822299B2 (en) | 2016-05-26 | 2020-11-03 | The Regents Of The University Of California | Compounds and methods for hematopoietic regeneration |
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WO2019108800A1 (en) * | 2017-11-29 | 2019-06-06 | The Regents Of The University Of California | Compounds and methods for hematopoietic regeneration |
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