CN110724101A - 一种多取代异喹啉-1（2h）-酮衍生物及其制备方法 - Google Patents

一种多取代异喹啉-1（2h）-酮衍生物及其制备方法 Download PDF

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CN110724101A
CN110724101A CN201911101369.0A CN201911101369A CN110724101A CN 110724101 A CN110724101 A CN 110724101A CN 201911101369 A CN201911101369 A CN 201911101369A CN 110724101 A CN110724101 A CN 110724101A
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梅汝槐
马文博
邹亮
孙俊梅
吴笛
张振
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Abstract

本发明公开了一种多取代异喹啉‑1(2H)‑酮衍生物及其制备方法，涉及有机合成及电化学领域；所述多取代异喹啉‑1(2氢)‑酮衍生物，具有如式(Ⅰ)所示结构：
Figure DDA0002269964200000011
所述衍生物包括其立体异构体、溶剂化物、水合物或药学上可接受的盐或共晶；L4为N‑甲基‑N‑2‑吡啶基或氢。

Description

一种多取代异喹啉-1(2H)-酮衍生物及其制备方法
技术领域
本发明涉及有机合成及电化学领域，尤其是一种多取代异喹啉-1(2H)-酮衍生物及其制备方法。
背景技术
过渡金属催化碳氢键官能团化是现代有机合成的一门重要技术，氧化碳氢键官能团化在合成重要杂环化合物中有重要应用。但目前已知方法多采用贵金属，比如铱、钌、铑、钯等，这些金属通常价格昂贵，毒性大，不适宜大规模工业化生产。此外这些方法通常需要使用当量的化学氧化剂，如Cu(OAc)2.4H2O，AgOAc，Mn(OAc)2和O2等，这些金属氧化剂的引入不仅增加了成本，且不可避免的会带来当量、有毒的副产物的产生，给产品分离纯化带来麻烦且造成环境污染。此外使用O2作为氧化剂时，当其与易燃易爆的有机溶剂混合加热，亦会有起火爆炸的危险。
近年来电化学在有机合成领域得到了极大的发展，其在氧化还原、自由基等类型的反应中具有广泛应用。尤其是在电化学氧化还原反应中，因电流常常可以替代当量的昂贵有毒的氧化剂及还原剂的使用，从而可以最大限度的减少氧化还原反应过程中副产物的产生，极大的提高了反应的原子经济性。在已经商业化的氧化剂或者还原剂中，电能经济且易得；电能可以通过光伏、水力(潮汐)、风力发电等可再生方式产生并且易于存储，具有可再生清洁能源的基本属性；电化学有机合成一般产生的副产物少，很多情况下仅产生H2这一唯一的副产物；此发明把电化学有机合成与过渡金属催化碳氢键官能团化结合起来，提高了反应的原子经济性和反应步数经济性，产物中没有重金属残留，分离纯化简便，反应符合绿色环保可持续理念。
发明内容
本发明的目的之一在于提供一种多取代异喹啉-1(2H)-酮衍生物，所述多取代异喹啉-1(2氢)-酮衍生物，具有如式(Ⅰ)所示结构：
Figure BDA0002269964180000021
所述衍生物包括其立体异构体、溶剂化物、水合物或药学上可接受的盐或共晶；L4为N-甲基-N-2-吡啶基或氢。
作为本发明的一个实施例，当L4为N-甲基-N-2-吡啶基时，L1选自以下一种或多种基团：氢、卤素、C1-C6烷基、三氟甲基、C1-C6烷氧基、取代或未取代的苯基、腈基、酯基、甲硫基、取代或未取代的乙酰基；L2选自以下一种或多种基团：氢、取代或未取代的C1-C7烷基；L3选自以下一种或多种基团：取代或未取代的C1-C7烷基、取代或未取代的苄基、取代或未取代的二苯基磷酰甲基、乙酰酯基；
作为本发明的另一实施例，当L4为氢时，L1选自以下一种或多种基团：氢、C1-C6烷基、C1-C6烷氧基、取代或未取代的苯基、甲硫基；L2选自以下一种或多种基团：氢、取代或未取代的C1-C7烷基；L3选自以下一种或多种基团：取代或未取代的C1-C7烷基、取代或未取代的苄基。
本发明中，除非另有说明，取代基名称前未冠有“取代或未取代的”定义的均指未取代的情况，例如：“烷基”是指未取代的烷基。
本发明所述基团和化合物中所涉及的碳、氢、氧、硫、氮或F、Cl、Br、I均包括它们的同位素情况，及本发明所述基团和化合物中所涉及的碳、氢、氧、硫或氮任选进一步被一个或多个它们对应的同位素所替代，其中碳的同位素包括12C、13C和14C，氢的同位素包括氕(H)、氘(D，又叫重氢)、氚(T，又叫超重氢)，氧的同位素包括16O、17O和18O，硫的同位素包括32S、33S、34S和36S，氮的同位素包括14N和15N，氟的同位素包括17F和19F，氯的同位素包括35Cl和37Cl，溴的同位素包括79Br和81Br。
“共晶”是指活性药物成分(API)和共晶形成物(CCF)在氢键或其他非共价键的作用下结合而成的晶体，其中API和CCF的纯态在室温下均为固体，并且各组分间存在固定的化学计量比。共晶是一种多组分晶体，既包含两种中性固体之间形成的二元共晶，也包含中性固体与盐或溶剂化物形成的多元共晶。
“立体异构体”是指由分子中原子在空间上排列方式不同所产生的异构体，包括顺反异构体、对映异构体和构象异构体。
本发明的目的之二在于提供上述多取代异喹啉-1(2氢)-酮衍生物的制备方法，该方法底物适用范围广泛，可快速大量制备目前用其它方法难以制备的系列多取代异喹啉-1(2H)-酮衍生物；且本发明使用廉价低毒金属钴作为催化剂，具有成本低、避免产品重金属超标等优点；本发明使用电流代替当量有毒的金属氧化剂，成本低廉；反应仅产生氢气为唯一的副产物，副产物极少，产品分离纯化容易；本发明的反应导向基团可以用电化学还原的方法脱除。
作为本发明的一个实施例，当L4为N-甲基-N-2-吡啶基时，包括以下步骤：
将N'-甲基-N'-(2-吡啶基)苯甲酰肼和联烯、添加剂混合后，在氩气保护下，在混合物中加入催化剂、溶剂，在恒定电流模式下以非分隔式电解池进行反应，并浓缩、柱层析分离得到产物；进一步地，所述非分隔式电解池的阳极为网状玻璃态碳电极(RVC)，阴极为铂片电极；更进一步地，所述阳极规格为1.0×1.5厘米，所述阴极规格为1.0×1.0厘米；更进一步地，所述恒定电流模式下，恒定电流为2.0～10.0mA，优选为2.0mA；所述反应温度为23～80℃，优选为40℃；反应时间为8-15h，优选为15h。
所述N'-甲基-N'-(2-吡啶基)苯甲酰肼化合物与联烯的摩尔比为0.1-1.0：0.1-1.0；优选为0.55：0.50；所述催化剂与混合物的摩尔比为0.05～0.2，优选为0.1；所述添加剂与联烯的摩尔比为1.0～2.0，优选为2.0；所述溶剂为三氟乙醇，更进一步地，所述三氟乙醇用量为3-4体积份，优选为3.5体积份。需要说明的是，当摩尔份的单位为mmol时，体积份的单位为mL。
所述催化剂为醋酸钴、醋酸钴的水合物或其它含钴元素的催化剂。
所述添加剂为NaOAc、NaOPiv、PivOH、KOAc或KOPiv，优选为NaOAc；所述溶剂为MeOH、EtOH、HFIP、toluene、TFE，优选为TFE。
所述柱层析中的层析液为石油醚、乙酸乙酯和/或三乙胺；进一步地，所述三种层析液的体积比为0:100:1～200:100:0.33。
作为本发明的另一实施例，当L4为氢时，包括以下步骤：
将3-[(二苯基磷酰)甲基]-2-[甲基(2-吡啶基)胺基]异喹啉-1(2氢)-酮衍生物、碘化钾、n-Bu4NPF6置于反应容器中，安装电极，其中阳极为金属镁，阴极为铂片，在保护气体氛围下加入溶剂DMF，再加入SmI2的四氢呋喃溶液，在恒定电流下以非分隔式电解池模式反应；反应结束后，依次用EtOAc稀释，饱和食盐水洗涤，有机相干燥，过滤蒸干，硅胶柱层析纯化得产物；进一步地，所述恒定电流为5.0mA；进一步地，所述反应温度为室温，反应时间为10h。
所述3-[(二苯基磷酰)甲基]-2-[甲基(2-吡啶基)胺基]异喹啉-1(2氢)-酮衍生物、碘化钾、n-Bu4NPF6的摩尔比为1:2:2；所述SmI2的四氢呋喃溶液浓度为0.1mmol/mL，用量为10mol％；进一步地，所述溶剂为DMF，其用量为5.0mL。
所述硅胶柱层析纯化所用洗脱剂为体积比1:1的乙酸乙酯：石油醚。
本发明与现有技术相比，具有以下优点：
本发明使用廉价低毒具有良好生物相容性的金属钴作为催化剂，具有成本低、避免产品重金属超标等优点。
本发明使用电流代替当量有毒的金属氧化剂，成本低廉；反应仅产生氢气为唯一的副产物，副产物极少，产品分离纯化容易。
本发明底物适用范围广泛，可快速大量制备目前用其它方法难以制备的系列多取代异喹啉-1(2H)-酮衍生物。
本发明的反应导向基团可以用电化学还原的方法脱除。
附图说明
图1为当L4为N-甲基-N-2-吡啶基时，多取代异喹啉-1(2H)-酮衍生物化合物的合成示意图；
图2为当L4为氢基时，多取代异喹啉-1(2H)-酮衍生物化合物的合成示意图。
具体实施方式
下面结合具体实施例对本发明权利要求书做进一步的详细说明，但对本发明权利要求书不构成任何限定。
实施例1
一种钴催化一种多取代异喹啉-1(2H)-酮衍生物化合物，当L4为N-甲基-N-2-吡啶基时的制备方法，包括以下步骤：
将0.55mmol N'-甲基-N'-(2-吡啶基)苯甲酰肼类衍生物和0.50mmol联烯、2.0当量醋酸钠混合，加入10mol％催化剂醋酸钴，安装好网状玻璃态碳电极(阳极)和铂电极(阴极)，在氩气保护下加入三氟乙醇3.5mL。以非分隔式电解池恒定电流2.0mA模式于40℃反应15小时，反应结束后浓缩，硅胶柱层析(石油醚/乙酸乙酯/三乙胺＝100/10/1～50/50/1)分离纯化得到多取代异喹啉-1(2H)-酮衍生物3。
其制备步骤详见图1。
实施例1.1
将0.55mmol N'-甲基-N'-(2-吡啶基)苯甲酰肼类衍生物和0.50mmol二苯基氧化磷联烯、2.0当量醋酸钠混合，加入10mol％催化剂醋酸钴，安装好网状玻璃态碳电极(阳极)和铂电极(阴极)，在氩气保护下加入三氟乙醇3.5mL。以非分隔式电解池恒定电流2.0mA模式于40℃反应15小时，反应结束后浓缩，硅胶柱层析(石油醚/乙酸乙酯/三乙胺＝50/50/1)分离纯化得到3-[(二苯基氧化磷)甲基]-2-[甲基(2-吡啶)胺基]异喹啉-1(2H)-酮3aa(211.8mg,91％)。
实施例1.2
将0.55mmol N'-甲基-N'-(2-吡啶)-4-甲基-苯甲酰肼和0.50mmol二苯基氧化磷联烯、2.0当量醋酸钠混合，加入10mol％催化剂醋酸钴，安装好网状玻璃态碳电极和铂电极，在氩气保护下加入三氟乙醇。以非分隔式电解池形式40℃反应15小时(恒定电流2.0mA)，反应结束后浓缩，硅胶柱层析(石油醚/乙酸乙酯/三乙胺＝50/50/1)分离纯化得到3-[(二苯基磷酰)甲基]-6-甲基-2-[甲基(2-吡啶基)胺基]异喹啉-1(2氢)-酮(3ba)(160.6mg,67％)。
实施例2
一种钴催化一种多取代异喹啉-1(2H)-酮衍生物化合物，当L4为氢基时的制备方法，包括以下步骤：
将0.50mmol 3-[(二苯基磷酰)甲基]-2-[甲基(2-吡啶基)胺基]异喹啉-1(2氢)-酮衍生物3、2.0当量碘化钾、2.0当量n-Bu4NPF6置于反应容器中，安装电极，其中阳极为金属镁，阴极为铂片，在保护气体氛围下依次加入5.0mL DMF和10mol％SmI2的0.1mmol/mL的四氢呋喃溶液，以非分隔式电解池模式恒定电流5.0mA于室温反应10小时；反应结束后，反应液EtOAc稀释，饱和食盐水洗三次，有机相干燥，过滤蒸干，以乙酸乙酯/石油醚1/1洗脱剂硅胶柱层析纯化得产物4。
其制备步骤详见图2。
实施例2.1
将0.50mmol 3-苄基-2-[甲基(2-吡啶基)胺基]异喹啉-1(2氢)-酮3ae、2.0当量碘化钾、2.0当量n-Bu4NPF6置于反应容器中，安装电极，其中阳极为金属镁，阴极为铂片，在保护气体氛围下依次加入5.0mL DMF和10mol％SmI2的0.1mmol/mL的四氢呋喃溶液，以非分隔式电解池模式恒定电流5.0mA于室温反应10小时；反应结束后，反应液EtOAc稀释，饱和食盐水洗三次，有机相干燥，过滤蒸干，以乙酸乙酯/石油醚1/1洗脱剂硅胶柱层析纯化得产物3-苄基异喹啉-1(2氢)-酮4ae(87.0mg,74％)。
以上实施例仅为本发明非典型的具体实施方式，目的在于使本发明所属技术领域技术人员能够更好的实施技术方案，但本发明所述方法所能制备的产物不限于以上产物，下面将对通过本发明方法制备而得的各产物进行表征，具体表征数据如下：
(1)3aa：1H NMR(600MHz,CDCl3)δ＝8.25–8.23(m,1H),8.21(ddd,J＝4.9,1.8,0.8Hz,1H),7.77–7.72(m,2H),7.72–7.67(m,2H),7.61–7.58(m,1H),7.57–7.49(m,2H),7.46–7.37(m,7H),6.81–6.71(m,2H),6.26(d,J＝8.5Hz,1H),3.93(dd,J＝15.9,13.7Hz,1H),3.70(dd,J＝16.0,12.7Hz,1H),3.33(s,3H).13C NMR(150MHz,CDCl3)δ＝161.4(Cq),159.0(Cq),148.0(CH),137.9(CH),136.2(d,2JC-P＝5.1Hz,Cq),136.1(Cq),132.9(CH),132.6(d,1JC-P＝101.3Hz,Cq),132.2(d,4JC-P＝3.3Hz,CH),132.2(d,4JC-P＝3.3Hz,CH),131.6(d,1JC-P＝101.6Hz,Cq),131.2(d,3JC-P＝9.2Hz,CH),130.8(d,3JC-P＝9.7Hz,CH),128.8(d,2JC-P＝12.5Hz,CH),128.7(d,2JC-P＝12.5Hz,CH),127.8(CH),126.6(CH),126.1(CH),126.0(Cq),115.8(CH),108.2(d,3JC-P＝6.0Hz,CH),106.8(CH),38.2(CH3),32.2(d,1JC-P＝67.7Hz,CH2).31P{1H}-NMR(243MHz,CDCl3)δ＝28.4.HR-MS(ESI)m/z calcd forC28H25N3O2P。
由上可知3aa为3-[(二苯基磷酰)甲基]-2-[甲基(2-吡啶基)胺基]异喹啉-1(2氢)-酮，结构式为：
Figure BDA0002269964180000081
(2)3ba：1H NMR(600MHz,CDCl3)δ＝8.23–8.18(m,1H),8.13(d,J＝8.1Hz,1H),7.77–7.72(m,2H),7.71–7.67(m,2H),7.54–7.48(m,2H),7.44–7.41(m,4H),7.38(ddd,J＝8.8,7.4,1.8Hz,1H),7.23–7.17(m,2H),6.77–6.71(m,2H),6.23(d,J＝8.5Hz,1H),3.92(dd,J＝15.9,13.7Hz,1H),3.70(dd,J＝16.0,12.7Hz,1H),3.34(s,3H),2.42(s,3H).13CNMR(150MHz,CDCl3)δ＝161.3(Cq),159.0(Cq),147.9(CH),143.5(Cq),137.8(CH),136.2(Cq),136.1(d,2JC-P＝4.8Hz,Cq),132.7(d,1JC-P＝101.2Hz,Cq),132.1(d,4JC-P＝2.7Hz,CH),132.1(d,4JC-P＝2.7Hz,CH),131.6(d,1JC-P＝102.1Hz,Cq),131.1(d,3JC-P＝8.9Hz,CH),130.7(d,3JC-P＝9.3Hz,CH),128.8(d,2JC-P＝12.6Hz,CH),128.7(d,2JC-P＝12.3Hz,CH),128.1(CH),127.7(CH),125.8(CH),123.7(Cq),115.6(CH),108.1(d,3JC-P＝5.9Hz,CH),106.7(CH),38.1(CH3),32.1(d,1JC-P＝67.8Hz,CH2),21.7(CH3).31P{1H}-NMR(243MHz,CDCl3)δ＝28.3.HR-MS(ESI)m/z calcd for C29H27N3O2P[M+H+]480.1835,found 480.1824。
由上可知，3ba为3-[(二苯基磷酰)甲基]-6-甲基-2-[甲基(2-吡啶基)胺基]异喹啉-1(2氢)-酮，结构式为：
Figure BDA0002269964180000091
(3)3ca：1H NMR(600MHz,CDCl3)δ＝8.23–8.20(m,1H),8.18(d,J＝8.2Hz,1H),7.78–7.73(m,2H),7.73–7.68(m,2H),7.55–7.50(m,2H),7.46–7.43(m,4H),7.39(ddd,J＝8.8,7.3,1.8Hz,1H),7.29(dd,J＝8.3,1.4Hz,1H),7.27–7.25(m,1H),6.84(d,J＝2.6Hz,1H),6.75(dd,J＝6.9,5.1Hz,1H),6.24(d,J＝8.5Hz,1H),3.92(dd,J＝16.0,13.5Hz,1H),3.71(dd,J＝16.0,13.0Hz,1H),3.33(s,3H),2.99(h,J＝6.9Hz,1H),1.28(d,J＝6.9Hz,6H).13C NMR(150MHz,CDCl3)δ＝161.3(Cq),159.1(Cq),154.3(Cq),148.0(CH),137.8(CH),136.4(Cq),136.0(d,2JC-P＝4.2Hz,Cq),132.7(d,1JC-P＝101.2Hz,Cq),132.1(CH),132.1(CH),131.2(d,1JC-P＝100.3Hz,Cq),131.1(d,3JC-P＝8.9Hz,CH),130.8(d,3JC-P＝9.7Hz,CH),128.8(d,2JC-P＝11.9Hz,CH),128.7(d,2JC-P＝12.5Hz,CH),127.9(CH),125.8(CH),124.1(Cq),123.3(CH),115.6(CH),108.4(d,3JC-P＝5.9Hz,CH),106.8(CH),38.2(CH3),34.3(CH),32.0(d,1JC-P＝67.9Hz,CH2),23.6(CH3),23.6(CH3).31P{1H}-NMR(243MHz,CDCl3)δ＝28.3.HR-MS(ESI)m/z calcd for C31H31N3O2P[M+H+]508.2148,found 508.2153。
由上可知，3ca为3-[(二苯基磷酰)甲基]-6-异丙基-2-[甲基(2-吡啶基)胺基]异喹啉-1(2氢)-酮，结构式为：
Figure BDA0002269964180000092
(4)3da：1H NMR(600MHz,CDCl3)δ＝8.30(d,J＝8.3Hz,1H),8.23–8.20(m,1H),7.78–7.73(m,2H),7.73–7.69(m,2H),7.64–7.59(m,4H),7.54–7.49(m,2H),7.48–7.37(m,8H),6.85(d,J＝2.4Hz,1H),6.76(dd,J＝7.1,5.1Hz,1H),6.29(d,J＝8.5Hz,1H),3.95(dd,J＝16.0,13.7Hz,1H),3.73(dd,J＝16.0,12.6Hz,1H),3.36(s,3H).13C NMR(150MHz,CDCl3)δ＝161.3(Cq),159.0(Cq),148.0(CH),145.6(Cq),139.9(Cq),137.9(CH),136.7(d,2JC-P＝4.2Hz,Cq),136.5(Cq),132.7(d,1JC-P＝100.2Hz,Cq),132.1(CH),132.1(CH),131.7(d,1JC-P＝101.5Hz,Cq),131.1(d,3JC-P＝9.1Hz,CH),130.8(d,3JC-P＝9.6Hz,CH),128.9(CH),128.8(d,2JC-P＝11.8Hz,CH),128.7(d,2JC-P＝11.7Hz,CH),128.4(CH),128.2(CH),127.4(CH),125.8(CH),124.8(Cq),124.2(CH),115.7(CH),108.3(d,3JC-P＝6.0Hz,CH),106.8(CH),38.2(CH3),32.2(d,1JC-P＝67.7Hz,CH2).31P{1H}-NMR(243MHz,CDCl3)δ＝28.4.HR-MS(ESI)m/zcalcd for C34H29N3O2P[M+H+]542.1992,found 542.1980.
由上可知，3da为3-[(二苯基磷酰)甲基]-2-[甲基(2-吡啶基)胺基]-6-苯基异喹啉-1(2氢)-酮，结构式为：
Figure BDA0002269964180000101
(5)3ea：1H NMR(600MHz,CDCl3)δ＝8.24–8.21(m,1H),8.16(d,J＝8.9Hz,1H),7.78–7.73(m,2H),7.72–7.68(m,2H),7.56–7.50(m,2H),7.50–7.40(m,4H),7.40(ddd,J＝8.7,7.3,1.8Hz,1H),6.97(dd,J＝8.9,2.4Hz,1H),6.84(d,J＝2.4Hz,1H),6.81(d,J＝2.4Hz,1H),6.76(dd,J＝7.2,5.0Hz,1H),6.23(d,J＝8.5Hz,1H),3.91(dd,J＝16.1,13.5Hz,1H),3.87(s,3H),3.71(dd,J＝16.1,13.0Hz,1H),3.32(s,3H).13C NMR(150MHz,CDCl3)δ＝163.2(Cq),161.0(Cq),159.1(Cq),148.0(CH),138.2(Cq),137.9(CH),136.7(d,2JC-P＝4.0Hz,Cq),132.6(d,1JC-P＝101.6Hz,Cq),132.2(CH),132.2(CH),131.6(d,1JC-P＝102.3Hz,Cq),131.1(d,3JC-P＝9.5Hz，CH)，130.8(d,3JC-P＝9.7Hz,CH),129.8(CH),128.8(d,2JC-P＝11.8Hz,CH),128.7(d,2JC-P＝12.2Hz,CH),119.7(Cq),116.2(CH),115.6(CH),108.0(d,3JC-P＝5.8Hz,CH),106.9(CH),106.8(CH),55.5(CH3),38.2(CH3),31.9(d,1JC-P＝67.9Hz,CH2).31P{1H}-NMR(243MHz,CDCl3)δ＝28.4.HR-MS(ESI)m/z calcd for C29H27N3O3P[M+H+]496.1785,found 496.1775.
由此可知，3ea为3-[(二苯基磷酰)甲基]-6-甲氧基-2-[甲基(2-吡啶基)胺基]异喹啉-1(2氢)-酮，结构式为：
Figure BDA0002269964180000111
(6)3fa：1H NMR(600MHz,CDCl3)δ＝8.21(ddd,J＝5.0,1.8,0.8Hz,1H),8.16(d,J＝8.9Hz,1H),7.75–7.71(m,2H),7.71–7.66(m,2H),7.53–7.49(m,2H),7.45–7.37(m,9H),7.36–7.32(m,1H),7.04(dd,J＝8.9,2.5Hz,1H),6.86(d,J＝2.4Hz,1H),6.76(d,J＝2.6Hz,1H),6.74(ddd,J＝7.2,5.0,0.7Hz,1H),6.22(d,J＝8.5Hz,1H),5.12(s,2H),3.89(dd,J＝16.0,13.5Hz,1H),3.68(dd,J＝16.1,13.1Hz,1H),3.30(s,3H).13C NMR(150MHz,CDCl3)δ＝162.3(Cq),161.0(Cq),159.1(Cq),148.0(CH),138.2(Cq),137.9(CH),136.8(d,2JC-P＝4.7Hz,Cq),136.1(Cq),132.6(d,1JC-P＝101.4Hz,Cq),132.2(d,4JC-P＝2.5Hz,CH),132.1(d,4JC-P＝2.4Hz,CH),131.6(d,1JC-P＝101.7Hz,Cq),131.1(d,3JC-P＝9.5Hz,CH),130.8(d,3JC-P＝9.6Hz,CH),130.0(CH),128.8(d,2JC-P＝12.6Hz,CH),128.7(d,2JC-P＝12.8Hz,CH),128.6(CH),128.2(CH),127.4(CH),119.9(Cq),116.7(CH),115.7(CH),108.1(CH),108.02(d,3JC-P＝6.0Hz,CH),106.8(CH),70.1(CH2),38.2(CH3),32.0(d,1JC-P＝67.7Hz,CH2).31P{1H}-NMR(243MHz,CDCl3)δ＝28.4.HR-MS(ESI)m/z calcd for C35H31N3O3P[M+H+]572.2098,found572.2086.
由此可知，3fa为6-苄氧基-3-[(二苯基磷酰)甲基]-2-[甲基(2-吡啶基)胺基]异喹啉-1(2氢)-酮，结构式为：
Figure BDA0002269964180000121
(7)3ga:：1H NMR(600MHz,CDCl3)δ＝8.24(dd,J＝8.8,5.6Hz,1H),8.20–8.17(m,1H),7.75–7.72(m,2H),7.70–7.67(m,2H),7.55–7.49(m,2H),7.47–7.40(m,5H),7.08–7.05(m,1H),7.00(d,J＝9.2Hz,1H),6.78–6.74(m,1H),6.64(s,1H),6.30(d,J＝8.5Hz,1H),3.93(dd,J＝15.8,13.7Hz,1H),3.68(dd,J＝15.9,12.4Hz,1H),3.33(s,3H).13C NMR(150MHz,CDCl3)δ＝165.5(d,1JC-F＝253.6Hz,Cq),160.7(Cq),158.9(Cq),148.1(CH),138.4(d,3JC-F＝10.0Hz,Cq),138.0(d,2JC-P＝4.9Hz,Cq),137.9(CH),132.6(d,1JC-P＝102.4Hz,Cq),132.2(CH),132.2(CH),131.6(d,1JC-P＝101.9Hz,Cq),131.1(d,3JC-P＝8.9Hz,CH),131.1(d,3JC-F＝8.9Hz,CH),130.7(d,3JC-P＝9.3Hz,CH),128.8(d,2JC-P＝11.9Hz,CH),128.7(d,2JC-P＝12.0Hz,CH),122.6(Cq),115.9(CH),115.2(d,2JC-F＝23.7Hz,CH),110.9(d,2JC-F＝21.9Hz,CH),107.3(dd,3,4JC-P/C-F＝2.9,2.3Hz,CH),106.8(CH),38.3(CH3),32.4(d,1JC-P＝67.3Hz,CH2).19F-NMR(565MHz,CDCl3)δ＝-(105.34-150.30)(m).31P{1H}-NMR(243MHz,CDCl3)δ＝28.3.HR-MS(ESI)m/z calcd for C28H24FN3O2P[M+H+]484.1585,found 484.1580.
由上可知，3ga为3-[(二苯基磷酰)甲基]-6-氟-2-[甲基(2-吡啶基)胺基]异喹啉-1(2氢)-酮，结构式为：
Figure BDA0002269964180000131
(8)3ha：1H NMR(600MHz,CDCl3)δ＝8.19–8.17(m,1H),8.15(d,J＝8.5Hz,1H),7.73(ddd,J＝11.6,8.1,1.1Hz,2H),7.71–7.66(m,2H),7.56–7.49(m,2H),7.47–7.41(m,5H),7.35(s,1H),7.31(d,J＝8.6Hz,1H),6.78–6.74(m,1H),6.60(d,J＝2.6Hz,1H),6.30(d,J＝8.5Hz,1H),3.93(dd,J＝15.8,13.8Hz,1H),3.68(dd,J＝15.9,12.4Hz,1H),3.33(s,3H).13CNMR(150MHz,CDCl3)δ＝160.8(Cq),158.8(Cq),148.1(CH),139.3(Cq),138.2(d,2JC-P＝5.4Hz,Cq),138.0(CH),137.3(Cq),132.6(d,1JC-P＝106.7Hz,Cq),132.2(CH),132.2(CH),131.6(d,1JC-P＝101.8Hz,Cq),131.1(d,3JC-P＝9.0Hz,CH)131.1,130.7(d,3JC-P＝9.0Hz,CH),129.7(CH),128.9(d,2JC-P＝11.1Hz,CH),128.8(d,2JC-P＝11.3Hz,CH),127.0(CH),125.2(CH),124.3(Cq),115.9(CH),106.9(d,3JC-P＝6.0Hz,CH),106.8(CH),38.2(CH3),32.4(d,1JC-P＝67.1Hz,CH2).31P{1H}-NMR(243MHz,CDCl3)δ＝28.3.HR-MS(ESI)m/z calcd forC28H24 35ClN3O2P[M+H+]500.1289,found 500.1280；calcd for C28H24 37ClN3O2P[M+H+]502.1260,found 502.1253.
由上可知，3ha为6-氯-3-[(二苯基磷酰)甲基]-2-[甲基(2-吡啶基)胺基]异喹啉-1(2氢)-酮，其结构式为
Figure BDA0002269964180000132
(9)3ia：1H NMR(600MHz,CDCl3)δ＝8.18(d,J＝4.7Hz,1H),7.91(d,J＝8.4Hz,1H),7.77(s,1H),7.73(dd,J＝11.5,7.9Hz,2H),7.68(dd,J＝12.8,7.9Hz,3H),7.56–7.50(m,2H),7.47–7.42(m,5H),6.79–6.74(m,1H),6.58(d,J＝2.0Hz,1H),6.29(d,J＝8.4Hz,1H),3.93(dd,J＝15.3,13.5Hz,1H),3.68(dd,J＝15.8,12.5Hz,1H),3.32(s,3H).13C NMR(150MHz,CDCl3)δ＝161.2(Cq),158.7(Cq),148.1(CH),138.0(CH),137.9(Cq),137.5(Cq),135.4(CH),134.7(CH),132.6(d,1JC-P＝100.0Hz,Cq),132.2(CH),132.2(CH),131.5(d,1JC-P＝100.7Hz,Cq),131.1(d,3JC-P＝9.1Hz,CH),130.7(d,3JC-P＝9.3Hz,CH),129.3(CH),128.9(d,2JC-P＝11.2Hz),128.8(d,2JC-P＝10.2Hz),125.1(Cq),116.0(CH),106.8(CH),106.6(d,3JC-P＝6.0Hz,CH),100.9(Cq),38.2(CH3),32.39(d,1JC-P＝67.0Hz,CH2).31P{1H}-NMR(243MHz,CDCl3)δ＝28.3.HR-MS(ESI)m/z calcd for C28H24IN3O2P[M+H+]592.0645,found592.0630.
由上可知，其为3-[(二苯基磷酰)甲基]-6-碘-2-[甲基(2-吡啶基)胺基]异喹啉-1(2氢)-酮，结构式为
Figure BDA0002269964180000141
(10)3ja：1H NMR(600MHz,CDCl3)δ＝8.25–8.17(m,1H),8.10(d,J＝8.5Hz,1H),7.80–7.70(m,2H),7.75–7.65(m,2H),7.55–7.51(m,2H),7.46–7.39(m,5H),7.22(d,J＝8.5Hz,1H),7.15(s,1H),6.83–6.75(m,1H),6.76(dd,J＝7.2,5.0Hz,1H),6.25(d,J＝8.5Hz,1H),3.92(dd,J＝16.0,13.5Hz,1H),3.71(dd,J＝16.0,12.8Hz,1H),3.33(s,3H),2.51(s,3H).13C NMR(150MHz,CDCl3)δ＝161.1(Cq),158.9(Cq),147.9(CH),145.7(Cq),137.8(CH),137.1(d,2JC-P＝4.4Hz,Cq),136.5(Cq),132.5(d,1JC-P＝101.4Hz,Cq),132.1(CH),132.1(CH),131.6(d,1JC-P＝102.0Hz,Cq),131.1(d,3JC-P＝9.4Hz,CH),130.7(d,3JC-P＝9.1Hz,CH),128.8(d,2JC-P＝11.2Hz,CH),128.7(d,2JC-P＝11.3Hz,CH),127.9(CH),124.3(CH),122.6(Cq),120.6(CH),115.7(CH),107.5(d,3JC-P＝5.9Hz,CH),106.7(CH),38.1(CH3),32.0(d,1JC-P＝67.7Hz,CH2),14.7(CH3).31P{1H}-NMR(243MHz,CDCl3)δ＝28.4.HR-MS(ESI)m/z calcd for C29H27N3O2PS[M+H+]512.1556,found 512.1544.
由上可知，其为3-[(二苯基磷酰)甲基]-2-[甲基(2-吡啶基)胺基]6-(甲硫基)异喹啉-1(2氢)-酮，结构式为：
Figure BDA0002269964180000151
(11)3ka：1H NMR(600MHz,CDCl3)δ＝8.34(d,J＝8.3Hz,1H),8.20–8.17(m,1H),7.77–7.73(m,2H),7.72–7.67(m,2H),7.66(s,1H),7.58–7.52(m,3H),7.49–7.42(m,5H),6.79(dd,J＝7.1,5.0Hz,1H),6.73(d,J＝2.6Hz,1H),6.35(d,J＝8.5Hz,1H),3.97(dd,J＝15.8,13.8Hz,1H),3.71(dd,J＝15.9,12.3Hz,1H),3.35(s,3H).13C NMR(150MHz,CDCl3)δ＝160.7(Cq),158.7(Cq),148.1(CH),138.6(d,2JC-P＝5.4Hz,Cq),138.0(CH),136.1(Cq),134.4(q,2JC-F＝32.6Hz,Cq),132.3(d,1JC-P＝102.6Hz,Cq),132.3(CH),132.3(CH),131.5(d,1JC-P＝102.7Hz,Cq),131.1(d,2JC-P＝9.0Hz,CH),130.7(d,2JC-P＝9.7Hz,CH),129.0(CH),128.9(d,3JC-P＝9.0Hz,CH),128.8(d,3JC-P＝8.8Hz,CH),128.1(Cq),123.6(d,1JC-F＝273.0Hz,Cq),123.3(d,3JC-F＝3.6Hz,CH),122.4(d,3JC-F＝2.0Hz,CH),116.1(CH),107.5(d,3JC-P＝6.1Hz,CH),106.8(CH),38.3(CH3),32.5(d,1JC-P＝67.1Hz,CH2).19F-NMR(565MHz,CDCl3)δ＝-63.0(s,3F).31P{1H}-NMR(243MHz,CDCl3)δ＝28.3.HR-MS(ESI)m/z calcd for C29H24F3N3O2P[M+H+]534.1553,found 534.1540.
由上可知，其为3-[(二苯基磷酰)甲基]-2-[甲基(2-吡啶基)胺基]6-(三氟甲基)异喹啉-1(2氢)-酮，结构式为
Figure BDA0002269964180000161
(12)3la：1H NMR(600MHz,CDCl3)δ＝8.30(d,J＝8.3Hz,1H),8.17–8.14(m,1H),7.76–7.72(m,2H),7.71–7.66(m,3H),7.57–7.51(m,3H),7.49–7.43(m,5H),6.80–6.77(m,1H),6.59(d,J＝2.8Hz,1H),6.39(d,J＝8.5Hz,1H),3.98(dd,J＝15.6,13.9Hz,1H),3.69(dd,J＝15.8,12.0Hz,1H),3.35(s,3H).13C NMR(150MHz,CDCl3)δ＝160.4(Cq),158.5(Cq),148.1(CH),139.5(d,2JC-P＝5.8Hz,Cq),138.0(CH),136.2(Cq),132.5(d,1JC-P＝101.2Hz,Cq),132.3(CH),132.3(CH),131.5(d,1JC-P＝102.0Hz,Cq),131.1(d,3JC-P＝9.5Hz,CH),130.7(d,3JC-P＝9.7Hz,CH),130.6(CH),129.0(CH),128.9(d,2JC-P＝10.0Hz,CH),128.8(d,2JC-P＝9.3Hz,CH),128.3(Cq),128.0(CH),117.9(Cq),116.3(Cq),116.2(CH),106.8(CH),106.5(d,3JC-P＝6.1Hz,CH),38.3(CH3),32.7(d,1JC-P＝66.5Hz,CH2).31P{1H}-NMR(243MHz,CDCl3)δ＝28.9.HR-MS(ESI)m/z calcd for C29H24N4O2P[M+H+]491.1631,found 491.1620.
由上可知，其为3-[(二苯基磷酰)甲基]-2-[甲基(2-吡啶基)胺基]-1-氧-1，2-二氢异喹啉-6-腈，结构式为：
Figure BDA0002269964180000162
(13)3ma：1H NMR(600MHz,CDCl3)δ＝8.27(d,J＝8.3Hz,1H),8.18–8.16(m,1H),8.07–8.05(m,1H),7.95(dd,J＝8.3,1.3Hz,1H),7.76–7.71(m,2H),7.71–7.66(m,2H),7.55–7.48(m,2H),7.46–7.41(m,5H),6.75(dd,J＝7.0,5.1Hz,1H),6.70(d,J＝2.7Hz,1H),6.33(d,J＝8.5Hz,1H),3.96(dd,J＝15.7,14.0Hz,1H),3.92(s,3H),3.70(dd,J＝15.9,12.1Hz,1H),3.36(s,3H).13C NMR(150MHz,CDCl3)δ＝166.2(Cq),160.9(Cq),158.7(Cq),148.0(CH),137.9(CH),137.7(d,2JC-P＝5.5Hz,Cq),135.9(Cq),133.8(Cq),132.7(d,1JC-P＝101.1Hz,Cq),132.2(d,4JC-P＝2.7Hz,CH),132.2(d,4JC-P＝2.3Hz,CH),131.6(d,1JC-P＝101.9Hz,Cq),131.1(d,3JC-P＝9.0Hz,CH),130.7(d,3JC-P＝9.6Hz,CH),128.8(d,2JC-P＝9.2Hz,CH),128.7(d,2JC-P＝9.3Hz,CH),128.7(Cq),128.2(CH),127.9(CH),126.4(CH),115.9(CH),107.8(d,2JC-P＝6.4Hz,CH),106.8(CH),52.5(CH3),38.2(CH3),32.4(d,1JC-P＝67.3Hz,CH2).31P{1H}-NMR(243MHz,CDCl3)δ＝28.3.HR-MS(ESI)m/z calcd for C30H27N3O4P[M+H+]524.1734,found524.1723.
由上可知，其为甲基-3-[(二苯基磷酰)甲基]-2-[甲基(2-吡啶基)胺基]-1-氧-1，2-二氢异喹啉-6-酯，结构式为：
Figure BDA0002269964180000171
(14)3na：1H NMR(600MHz,CDCl3)δ＝9.13(sbr,1H),8.18–8.16(m,1H),8.04–8.00(m,1H),7.78(s,1H),7.74–7.66(m,4H),7.55–7.52(m,2H),7.46–7.43(m,4H),7.41–7.37(m,1H),7.35(d,J＝8.7Hz,1H),6.78–6.71(m,1H),6.56(s,1H),6.25(d,J＝8.5Hz,1H),3.94(dd,J＝15.7,13.6Hz,1H),3.70(dd,J＝15.8,12.5Hz,1H),3.33(s,3H),2.03(s,3H).13C NMR(150MHz,CDCl3)δ＝169.4(Cq),161.1(Cq),159.0(Cq),147.9(CH),142.9(Cq),137.9(CH),137.2(Cq),136.5(d,2JC-P＝6.0Hz,Cq),132.5(d,1JC-P＝101.0Hz,Cq)132.3(CH),132.3(CH),131.5(d,1JC-P＝101.9Hz,Cq),131.0(d,3JC-P＝9.5Hz,CH),130.7(d,3JC-P＝9.5Hz,CH),128.9(d,2JC-P＝10.8Hz,CH),128.8(d,2JC-P＝10.9Hz,CH),128.6(CH),121.4(Cq),119.0(CH),115.8(CH),114.9(CH),108.5(d,3JC-P＝5.4Hz,CH),106.8(CH),38.3(CH3),32.5(d,1JC-P＝67.3Hz,CH2),24.3(CH3).31P{1H}-NMR(243MHz,CDCl3)δ＝28.9.HR-MS(ESI)m/z calcd for C30H28N4O3P[M+H+]523.1894,found523.1881.
由上可知，其为氮-{3-[(二苯基磷酰)甲基]-2-[甲基(2-吡啶基)胺基]-1-氧-1，2-二氢-6-异喹啉基}乙酰胺，结构式为：
Figure BDA0002269964180000181
(15)3oa：1H NMR(600MHz,CDCl3)δ＝8.20(d,J＝4.7Hz,1H),8.04(s,1H),7.73(dd,J＝11.6,7.3Hz,2H),7.69(dd,J＝11.6,7.3Hz,2H),7.54–7.48(m,2H),7.44–7.41(m,5H),7.40–7.36(m,1H),7.31(d,J＝8.1Hz,1H),6.76(s,1H),6.75–6.72(m,1H),6.22(d,J＝8.5Hz,1H),3.91(dd,J＝16.0,13.7Hz,1H),3.68(dd,J＝16.0,12.7Hz,1H),3.33(s,3H),2.40(s,3H).13C NMR(150MHz,CDCl3)δ＝161.4(Cq),159.1(Cq),148.0(CH),137.9(CH),136.7(Cq),135.0(d,2JC-P＝5.0Hz,Cq),134.4(CH),133.8(Cq),132.8(d,1JC-P＝101.0Hz,Cq),132.1(d,4JC-P＝2.8Hz,CH),132.0(d,4JC-P＝3.1Hz,CH),131.8(d,J＝102.4Hz,Cq),131.2(d,3JC-P＝9.3Hz,CH),130.8(d,3JC-P＝9.2Hz,CH),128.8(d,2JC-P＝12.1Hz,CH),128.7(d,2JC-P＝12.2Hz,CH),127.4(CH),126.1(CH),126.0(Cq),115.6(CH),108.2(d,3JC-P＝6.0Hz,CH),106.8(CH),38.1(CH3),32.0(d,1JC-P＝67.8Hz,CH2),21.3(CH3).31P{1H}-NMR(243MHz,CDCl3)δ＝28.2.HR-MS(ESI)m/z calcd for C29H27N3O2P[M+H+]480.1835,found480.1825.
由上可知，其为[(二苯基磷酰)甲基]-7-甲基-2-[甲基(2-吡啶基)胺基]-异喹啉-1(2氢)-酮，结构式为：
Figure BDA0002269964180000191
(16)3pa：1H NMR(600MHz,CDCl3)δ＝8.34(d,J＝8.3Hz,1H),8.19–8.15(m,1H),7.77–7.72(m,2H),7.72–7.67(m,2H),7.65(s,1H),7.57–7.50(m,3H),7.48–7.42(m,5H),6.77(ddd,J＝7.2,5.1,0.6Hz,1H),6.73(d,J＝2.8Hz,1H),6.35(d,J＝8.5Hz,1H),3.97(dd,J＝15.8,13.8Hz,1H),3.71(dd,J＝15.9,12.2Hz,1H),3.35(s,3H).13C NMR(150MHz,CDCl3)δ＝160.7(Cq),158.6(Cq),148.1(CH),138.6(d,2JC-p＝5.4Hz,Cq),138.0(CH),136.1(Cq),134.4(q,2JC-F＝32.6Hz,Cq),132.6(d,1JC-P＝100.8Hz,Cq),132.3(CH),132.3(CH),131.6(d,1JC-P＝102.2Hz,Cq),131.1(d,3JC-p＝9.0Hz,CH),130.7(d,3JC-p＝9.0Hz,CH),129.0(CH),128.9(d,2JC-p＝9.7Hz,CH),128.8(d,2JC-p＝9.0Hz,CH),128.1(Cq),123.5(q,1JC-F＝273.1Hz,Cq),123.3(q,3JC-F＝3.8Hz,CH),122.4(q,3JC-F＝2.1Hz,CH),116.1(CH),107.4(d,3JC-P＝6.0Hz,CH),106.8(CH),38.2(CH3),32.5(d,1JC-P＝67.0Hz,CH2).19F-NMR(565MHz,CDCl3)δ＝-62.4(s,3F).31P{1H}-NMR(243MHz,CDCl3)δ＝28.3.HR-MS(ESI)m/zcalcd for C29H24F3N3O2P[M+H+]534.1553,found 534.1541.
由上可知，其为3-[(二苯基磷酰)甲基]-2-[甲基(2-吡啶基)胺基]-7-(三氟甲基)异喹啉-1(2氢)-酮，结构式为：
Figure BDA0002269964180000201
(17)3qa：1H NMR(600MHz,CDCl3)δ＝8.78(s,1H),8.20–8.16(m,2H),7.74(dd,J＝11.6,8.1Hz,2H),7.69(dd,J＝11.7,8.1Hz,2H),7.56–7.49(m,2H),7.48–7.41(m,6H),6.78(dd,J＝7.1,3.6Hz,1H),6.68(s,1H),6.36(d,J＝8.4Hz,1H),4.02–3.95(m,1H),3.72(dd,J＝15.7,12.4Hz,1H),3.35(s,3H),2.60(s,3H).13C NMR(150MHz,CDCl3)δ＝196.9(Cq),161.3(Cq),158.7(Cq),148.1(CH),139.7(d,2JC-P＝5.0Hz,Cq),139.6(Cq),138.0(CH),134.7(Cq),132.6(d,1JC-P＝97.9Hz,Cq),132.3(CH),132.3(CH),131.6(d,1JC-P＝102.1Hz,Cq),131.3(CH),130.7(d,3JC-P＝9.1Hz,CH),131.1(d,3JC-P＝9.1Hz,CH),129.5(CH),128.9(d,2JC-P＝12.1Hz,CH),128.8(d,2JC-P＝12.3Hz,CH),126.5(CH),125.5(Cq),116.1(CH),107.6(d,3JC-P＝6.1Hz,CH),106.9(CH),38.3(CH3),32.8(d,1JC-P＝66.6Hz,CH2),26.4(CH3).31P{1H}-NMR(243MHz,CDCl3)δ＝28.3.HR-MS(ESI)m/z calcd for C30H27N3O3P[M+H+]508.1785,found 508.1775.
由上可知，其为7-(乙酰基)-3-[(二苯基磷酰)甲基]-2-[甲基(2-吡啶基)胺基]-异喹啉-1(2氢)-酮，结构式为：
Figure BDA0002269964180000202
(18)3ra：1H NMR(600MHz,CDCl3)δ＝8.51(s,1H),8.15(d,J＝4.8Hz,1H),7.76–7.71(m,3H),7.70–7.66(m,2H),7.56–7.50(m,2H),7.50–7.42(m,6H),6.81–6.77(m,1H),6.67(d,J＝2.5Hz,1H),6.39(d,J＝8.5Hz,1H),3.98(dd,J＝15.6,13.7Hz,1H),3.70(dd,J＝15.7,12.3Hz,1H),3.31(s,3H).13C NMR(150MHz,CDCl3)δ＝160.1(Cq),158.4(Cq),148.1(CH),141.0(Cq),141.0(d,2JC-P＝5.2Hz,Cq),139.1,138.1(CH),134.4(CH),133.1(CH),132.5(d,1JC-P＝101.5Hz,Cq),132.3(CH),132.3(CH),131.6(d,1JC-P＝101.8Hz,Cq),131.1(d,3JC-P＝9.2Hz,CH),130.7(d,3JC-P＝9.7Hz,CH),128.9(d,2JC-P＝11.5Hz,CH),128.8(d,2JC-P＝11.7Hz,CH),127.0(CH),126.0(Cq),118.3(Cq),116.3(CH),109.6(Cq),107.0(d,3JC-P＝5.9Hz,CH),106.8(CH),38.3(CH3),32.9(d,1JC-P＝66.3Hz,CH2).31P{1H}-NMR(243MHz,CDCl3)δ＝28.2.HR-MS(ESI)m/z calcd for C29H24N4O2P[M+H+]491.1631,found 491.1622.
由上可知，其为3-[(二苯基磷酰)甲基]-2-[甲基(2-吡啶基)胺基]-1-氧-1，2-二氢异喹啉-7-腈，结构式为：
(19)3sa：1H NMR(600MHz,CDCl3)δ＝8.20(d,J＝4.7Hz,1H),7.75–7.66(m,4H),7.53–7.48(m,2H),7.46–7.37(m,6H),7.19(d,J＝7.9Hz,1H),7.12(d,J＝7.4Hz,1H),6.73(dd,J＝7.0,5.1Hz,1H),6.65(d,J＝2.4Hz,1H),6.25(d,J＝8.4Hz,1H),3.88(dd,J＝15.9,13.8Hz,1H),3.65(dd,J＝16.0,12.5Hz,1H),3.33(s,3H),2.76(s,3H).13C NMR(150MHz,CDCl3)δ＝161.8(Cq),159.0(Cq),148.0(CH),142.0(Cq),137.8(CH),137.7(Cq),135.9(d,2JC-P＝4.6Hz,Cq),132.7(d,1JC-P＝101.1Hz,Cq),132.1(d,4JC-P＝2.2Hz,CH),132.0(d,4JC-P＝2.2Hz,CH),132.0(CH),131.7(d,1JC-P＝102.0Hz,Cq),131.1(d,3JC-P＝9.2Hz,CH),130.7(d,3JC-P＝9.5Hz,CH),129.5(CH),128.8(d,2JC-P＝11.8Hz,CH),128.7(d,2JC-P＝12.0Hz,CH),124.4(CH),115.5(CH),108.4(d,3JC-P＝6.0Hz,CH),106.7(CH),38.0(CH3),32.1(d,1JC-P＝67.9Hz,CH2),23.5(CH3).31P{1H}-NMR(243MHz,CDCl3)δ＝28.4.HR-MS(ESI)m/zcalcd for C29H27N3O2P[M+H+]480.1835,found 480.1824.
由此可知，其为3-[(二苯基磷酰)甲基]-8-甲基-2-[甲基(2-吡啶基)胺基]-异喹啉-1(2氢)-酮，结构式为：
Figure BDA0002269964180000221
(20)3ta：1H NMR(600MHz,CDCl3)δ＝8.16(ddd,J＝4.9,1.8,0.7Hz,1H),7.73–7.70(m,2H),7.68–7.63(m,2H),7.52–7.45(m,3H),7.44–7.38(m,4H),7.36(ddd,J＝8.8,7.2,1.9Hz,1H),6.93(d,J＝7.8Hz,1H),6.78(d,J＝8.2Hz,1H),6.71–6.67(m,2H),6.24(d,J＝8.5Hz,1H),3.87(dd,J＝16.2,13.3Hz,1H),3.87(s,3H),3.63(dd,J＝16.1,13.3Hz,1H),3.27(s,3H).13C NMR(150MHz,CDCl3)δ＝160.8(Cq),159.6(Cq),159.1(Cq),147.9(CH),139.0(Cq),137.8(CH),137.0(d,2JC-P＝4.5Hz,Cq),133.5(CH),132.6(d,1JC-P＝101.3Hz,Cq),132.1(CH),132.1(CH),131.7(d,1JC-P＝103.9Hz,Cq),131.1(d,3JC-P＝9.6Hz,CH),130.7(d,3JC-P＝9.6Hz,CH),128.7(d,2JC-P＝11.5Hz,CH),128.6(d,2JC-P＝11.6Hz,CH),118.4(CH),115.4(CH),115.2(Cq),107.8(d,3JC-P＝6.3Hz,CH),107.7(CH),106.7(CH),56.0(CH3),38.2(CH3),32.2(d,1JC-P＝67.5Hz,CH2).31P{1H}-NMR(243MHz,CDCl3)δ＝28.2.HR-MS(ESI)m/z calcd for C29H27N3O3P[M+H+]496.1785,found 496.1775.
由上可知，其为3-[(二苯基磷酰)甲基]-8-甲氧基-2-[甲基(2-吡啶基)胺基]-异喹啉-1(2氢)-酮，结构式为：
(21)3ua：1H NMR(600MHz,CDCl3)δ＝8.19–8.16(m,1H),7.76–7.71(m,2H),7.70–7.65(m,2H),7.54–7.47(m,3H),7.46–7.40(m,5H),7.14(d,J＝8.0Hz,1H),7.02–6.96(m,1H),6.75(ddd,J＝7.1,5.0,1.1Hz,1H),6.69(s,1H),6.32(d,J＝8.5Hz,1H),3.92(dd,J＝15.8,13.6Hz,1H),3.66(dd,J＝15.9,12.7Hz,1H),3.29(s,3H).13C NMR(150MHz,CDCl3)δ＝162.3(d,1JC-F＝264.8Hz,Cq),158.8(Cq),158.4(d,2JC-F＝4.5Hz,Cq),148.0(CH),138.7(Cq),137.9(CH),137.8(Cq),133.7(d,3JC-F＝9.8Hz,CH),132.6(d,1JC-P＝100.9Hz,Cq),132.2(CH),132.2(CH),131.7(d,1JC-P＝101.2Hz,Cq),131.1(d,3JC-P＝9.6Hz,CH),130.7(d,3JC-P＝9.2Hz,CH),128.8(d,2JC-p＝11.6Hz,CH),128.7(d,2JC-p＝11.7Hz,CH),121.9(d,4JC-F＝3.8Hz,CH),115.9(CH),115.0(d,2JC-p＝5.3Hz,Cq),113.2(d,2JC-F＝21.4Hz,CH),107.3(d,3JC-P＝5.4Hz,CH),106.8(CH),38.2(CH3),32.4(d,1JC-P＝67.1Hz,CH2).19F-NMR(565MHz,CDCl3)δ＝-110.4(d,J＝9.2Hz,1F).31P{1H}-NMR(243MHz,CDCl3)δ＝28.2.HR-MS(ESI)m/z calcd for C28H24FN3O2P[M+H+]484.1585,found 484.1574.
由上可知，其为3-[(二苯基磷酰)甲基]-8-氟-2-[甲基(2-吡啶基)胺基]-异喹啉-1(2氢)-酮，结构式为：
Figure BDA0002269964180000232
(22)3va：1H NMR(600MHz,CDCl3)δ＝8.16(d,J＝4.2Hz,1H),7.75–7.70(m,2H),7.70–7.65(m,2H),7.61(dd,J＝6.2,2.7Hz,1H),7.53–7.49(m,2H),7.45–7.40(m,5H),7.33–7.29(m,2H),6.74(dd,J＝7.1,5.0Hz,1H),6.66(d,J＝2.5Hz,1H),6.31(d,J＝8.5Hz,1H),3.89(dd,J＝15.9,13.4Hz,1H),3.64(dd,J＝16.0,12.6Hz,1H),3.30(s,3H).13C NMR(150MHz,CDCl3)δ＝159.4(Cq),158.7(Cq),148.0(CH),139.1(Cq),137.9(CH),137.7(d,2JC-P＝4.8Hz,Cq),133.4(CH),132.5(d,1JC-P＝101.5Hz,Cq),132.6(CH),132.2(d,4JC-P＝3.1Hz,CH),132.2(d,4JC-P＝3.1Hz,CH),131.7(d,1JC-P＝101.5Hz,Cq),131.1(d,3JC-P＝8.9Hz,CH),130.7(d,3JC-P＝9.6Hz,CH),128.8(d,2JC-P＝12.4Hz,CH),128.7(d,2JC-P＝12.4Hz,CH),126.1(CH),123.3(Cq),123.0(Cq),115.8(CH),107.5(d,3JC-P＝6.0Hz,CH),106.7(CH),38.1(CH3),32.4(d,1JC-P＝67.4Hz,CH2).31P{1H}-NMR(243MHz,CDCl3)δ＝28.3.HR-MS(ESI)m/zcalcd for C28H24 79BrN3O2P[M+H+]544.0784,found 544.0774；C28H24 81BrN3O2P[M+H+]546.0764,found 546.0748.
由上可知，其为8-溴-3-[(二苯基磷酰)甲基]-2-[甲基(2-吡啶基)胺基]-异喹啉-1(2氢)-酮，结构式为：
Figure BDA0002269964180000241
(23)3wa：1H NMR(600MHz,CDCl3)δ＝9.90(d,J＝8.6Hz,1H),8.22(d,J＝4.4Hz,1H),7.95(d,J＝8.6Hz,1H),7.82(d,J＝7.8Hz,1H),7.75(dd,J＝11.6,7.7Hz,2H),7.71(dd,J＝11.6,7.5Hz,2H),7.62–7.58(m,1H),7.54–7.48(m,3H),7.46–7.41(m,4H),7.39(t,J＝8.6Hz,2H),6.89(d,J＝2.2Hz,1H),6.75(dd,J＝6.9,5.1Hz,1H),6.26(d,J＝8.4Hz,1H),4.03(dd,J＝15.8,13.7Hz,1H),3.79(dd,J＝15.8,12.9Hz,1H),3.40(s,3H).13C NMR(150MHz,CDCl3)δ＝161.5(Cq),159.0(Cq),148.0(CH),138.0(d,2JC-P＝5.4Hz,Cq),138.0(Cq),137.9(CH),134.3(CH),132.5(d,1JC-P＝102.3Hz,Cq),132.2(CH),132.2(CH),132.0(Cq),131.6(d,1JC-P＝102.2Hz,Cq),131.7(Cq),131.1(d,3JC-P＝9.0Hz,CH),130.8(d,3JC-P＝9.2Hz,CH),128.8(d,2JC-P＝13.1Hz,CH),128.7(d,2JC-P＝13.9Hz,CH),128.4(CH),128.1(CH),126.9(CH),126.3(CH),124.6(CH),119.4(Cq),115.7(CH),108.5(d,3JC-P＝5.7Hz,CH),106.8(CH),38.2(CH3),32.6(d,1JC-P＝67.1Hz,CH2).31P{1H}-NMR(243MHz,CDCl3)δ＝28.3.HR-MS(ESI)m/z calcd for C32H27N3O2P[M+H+]516.1835,found 516.1824.
由上可知，其为3-[(二苯基磷酰)甲基]-2-[甲基(2-吡啶基)胺基]-苯甲酰基[h]异喹啉-1(2氢)-酮，结构式为：
Figure BDA0002269964180000251
(24)3xa：1H NMR(600MHz,CDCl3)δ＝8.24–8.21(m,1H),8.01(s,1H),7.77–7.72(m,2H),7.72–7.68(m,2H),7.56–7.50(m,2H),7.46–7.43(m,4H),7.38(ddd,J＝8.7,7.3,1.8Hz,1H),7.20(s,1H),6.78–6.73(m,2H),6.20(d,J＝8.5Hz,1H),3.91(dd,J＝16.0,13.7Hz,1H),3.70(dd,J＝16.0,12.9Hz,1H),3.33(s,3H),2.35(s,3H),2.33(s,3H).13C NMR(150MHz,CDCl3)δ＝161.3(Cq),159.1(Cq),148.0(CH),143.0(Cq),137.9(CH),136.2(Cq),135.8(d,2JC-P＝4.4Hz,Cq),134.3(Cq),132.1(CH),132.1(CH),132.7(d,1JC-P＝101.4Hz,Cq),131.7(d,1JC-P＝102.2Hz,Cq),131.2(d,3JC-P＝9.5Hz,CH),130.8(d,3JC-P＝9.7Hz,CH),128.8(d,2JC-P＝12.4Hz,CH),128.7(d,2JC-P＝12.6Hz,CH),127.8(CH),126.5(CH),124.1(Cq),115.6(CH),108.1(d,3JC-P＝6.0Hz,CH),106.8(CH),38.2(CH3),32.0(d,1JC-P＝68.1Hz,CH2),20.2(CH3),19.7(CH3).31P{1H}-NMR(243MHz,CDCl3)δ＝28.4.HR-MS(ESI)m/zcalcd for C30H29N3O2P[M+H+]494.1992,found 494.1982.
由上可知，其为3-[(二苯基磷酰)甲基]-6,7-二甲基-2-[甲基(2-吡啶基)胺基]-异喹啉-1(2氢)-酮，结构式为：
Figure BDA0002269964180000261
(25)3ya：1H NMR(600MHz,CDCl3)δ＝8.18(d,J＝4.8Hz,1H),7.83(d,J＝8.4Hz,1H),7.74–7.67(m,4H),7.52–7.48(m,2H),7.46–7.37(m,5H),6.89(d,J＝8.4Hz,1H),6.74–6.72(m,1H),6.64(s,1H),6.27(d,J＝8.5Hz,1H),6.05(s.2H),3.92(dd,J＝15.7,13.7Hz,1H),3.67(dd,J＝15.8,12.5Hz,1H),3.31(s,3H).13C NMR(150MHz,CDCl3)δ＝160.8(Cq),159.0(Cq),150.2(Cq),148.0(CH),141.2(Cq),137.8(CH),136.9(d,2JC-P＝5.3Hz,Cq),132.8(d,1JC-P＝101.0Hz,Cq),132.1(CH),132.1(CH),131.8(d,1JC-P＝100.7Hz,Cq),131.1(d,3JC-P＝9.5Hz,CH),130.7(d,3JC-P＝9.0Hz,CH),128.8(d,2JC-P＝12.6Hz,CH),128.7(d,2JC-P＝12.1Hz,CH),123.3(CH),120.9(Cq),120.2(Cq),115.7(CH),108.5(CH),106.8(CH),100.2(CH2),100.8(d,3JC-P＝6.6Hz,CH),38.3(CH3),32.65(d,1JC-P＝67.1Hz,CH2).31P{1H}-NMR(243MHz,CDCl3)δ＝27.9.HR-MS(ESI)m/z calcd for C29H25N3O4P[M+H+]510.1577,found510.1569.
由上可知，其为7-[(二苯基磷酰)甲基]-6-[甲基(2-吡啶基)胺基]-[1,3]二氧[4,5-g]异喹啉-5(6氢)-酮，结构式为：
Figure BDA0002269964180000271
(26)3za：1H NMR(600MHz,CDCl3)δ＝8.22–8.19(m,1H),7.75–7.66(m,4H),7.53–7.49(m,2H),7.44–7.41(m,4H),7.39–7.35(m,1H),6.99(s,1H),6.96(s,1H),6.74–6.70(m,1H),6.63(d,J＝2.4Hz,1H),6.22(d,J＝8.4Hz,1H),3.85(dd,J＝16.0,13.7Hz,1H),3.63(dd,J＝16.1,12.7Hz,1H),3.32(s,3H),2.72(s,3H),2.34(s,3H).13C NMR(150MHz,CDCl3)δ＝161.7(Cq),159.1(Cq),148.0(CH),142.5(Cq),141.9(Cq),137.9(Cq),137.8(CH),135.8(d,2JC-P＝4.7Hz,Cq),132.7(d,1JC-P＝101.2Hz,Cq),132.1(d,4JC-P＝3.5Hz,CH),132.0(d,4JC-P＝3.3Hz,CH),131.74(d,1JC-P＝102.4Hz,Cq),131.2(d,3JC-P＝8.7Hz,CH),131.1(CH),130.8(d,3JC-P＝9.0Hz,CH),128.8(d,2JC-P＝12.1Hz,CH),128.7(d,2JC-P＝12.1Hz,CH),124.3(CH),122.2(Cq),115.4(CH),108.3(d,3JC-P＝5.9Hz,CH),106.7(CH),77.2,77.0,76.8,38.1(CH3),32.0(d,1JC-P＝68.0Hz,CH2),23.3(CH3),21.4(CH3).31P{1H}-NMR(243MHz,CDCl3)δ＝28.4.HR-MS(ESI)m/z calcd for C30H29N3O2P[M+H+]494.1992,found 494.1982.
由上可知，其为3-[(二苯基磷酰)甲基]-6，8-二甲基-2-[甲基(2-吡啶基)胺基]-异喹啉-1(2氢)-酮，结构式为
Figure BDA0002269964180000272
(27)3ab：1H NMR(600MHz,CDCl3)δ＝8.29(d,J＝8.0Hz,1H),8.22–8.20(m,1H),7.66–7.62(m,1H),7.51(d,J＝7.9Hz,1H),7.46(ddd,J＝8.8,7.3,1.8Hz,1H),7.42(t,J＝7.6Hz,1H),6.77–6.74(m,2H),6.38(d,J＝8.5Hz,1H),4.14–4.04(m,4H),3.58(s,3H),3.42(dd,J＝21.5,15.9Hz,1H),3.19(dd,J＝22.9,15.9Hz,1H),1.29(t,J＝6.2Hz,3H),1.27(t,J＝6.2Hz,3H).13C NMR(150MHz,CDCl3)δ＝161.5(Cq),158.9(Cq),148.1(CH),137.8(CH),136.5(d,2JC-P＝6.2Hz,Cq),136.2(d,4JC-P＝2.9Hz,Cq),133.0(CH),128.0(CH),126.6(CH),126.1(Cq),125.9(CH),115.7(CH),107.3(d,3JC-P＝7.6Hz,CH),106.7(CH),62.5(d,2JC-P＝6.9Hz,CH2),62.4(d,2JC-P＝6.9Hz,CH2),38.3(CH3),28.7(d,1JC-P＝143.1Hz,CH2),16.4(d,3JC-P＝5.0Hz,CH3),16.3(d,3JC-P＝5.0Hz,CH3).31P{1H}-NMR(243MHz,CDCl3)δ＝24.5.HR-MS(ESI)m/z calcd for C20H25N3O4P[M+H+]402.1577,found 402.1569。
由上可知，其为二乙基{[2-(甲基[2-吡啶基]胺基)-1-氧-1,2-二氢异喹啉-3-基]甲基}磷酸酯，结构式为：
Figure BDA0002269964180000281
(28)3ac：1H NMR(600MHz,CDCl3)δ＝8.31(d,J＝7.9Hz,1H),8.23–8.21(m,1H),7.67–7.63(m,1H),7.50(d,J＝7.9Hz,1H),7.48–7.42(m,2H),7.35–7.30(m,3H),7.30–7.27(m,2H),6.77(dd,J＝7.1,5.0Hz,1H),6.52(s,1H),6.40(d,J＝8.5Hz,1H),5.09(d,J＝12.2Hz,1H),5.00(d,J＝12.2Hz,1H),3.73(d,J＝16.5Hz,1H),3.61(d,J＝16.5Hz,1H),3.38(s,3H).13C NMR(150MHz,CDCl3)δ＝169.1(Cq),161.3(Cq),158.7(Cq),148.0(CH),138.7(Cq),137.8(CH),136.3(Cq),135.3(Cq),132.9(CH),128.6(CH),128.4(CH),128.4(CH),128.0(CH),126.7(CH),126.4(Cq),125.9(CH),115.9(CH),107.8(CH),106.9(CH),67.0(CH2),38.6(CH2),38.3(CH3).HR-MS(ESI)m/z calcd for C24H22N3O3[M+H+]400.1656,found 400.1652.
由上可知，其为苄基-2-{2-[甲基(2-吡啶基)胺基]-1-氧-1,2-二氢异喹啉-3-基}乙酰酯，结构式为
Figure BDA0002269964180000291
(29)3ad：1H NMR(600MHz,CDCl3)δ＝8.31(d,J＝8.2Hz,1H),8.23–8.21(m,1H),7.64(t,J＝8.2Hz,1H),7.55–7.44(m,1H),7.48–7.42(m,2H),6.79–6.75(m,1H),6.52(s,1H),6.41(d,J＝8.5Hz,1H),4.12–4.01(m,2H),3.67(d,J＝16.3Hz,1H),3.56(d,J＝16.3Hz,1H),3.48(s,3H),1.18(t,J＝7.1Hz,3H).13C NMR(150MHz,CDCl3)δ＝169.2(Cq),161.3(Cq),158.7(Cq),148.0(CH),138.9(Cq),137.7(CH),136.4(Cq),132.9(CH),128.0(CH),126.7(CH),126.4(Cq),125.9(CH),115.8(CH),107.8(CH),106.9(CH),61.3(CH2),38.7(CH2),38.3(CH3),14.1(CH3).HR-MS(ESI)m/z calcd for C19H20N3O3[M+H+]338.1499,found 338.1492.
由上可知，其为乙基-2-{2-[甲基(2-吡啶基)胺基]-1-氧-1,2-二氢异喹啉-3-基}乙酰酯，结构式为
Figure BDA0002269964180000292
(30)3nd：1H NMR(600MHz,CDCl3)δ＝8.23–8.20(m,1H),8.16(d,J＝8.5Hz,1H),7.46(ddd,J＝8.9,7.3,1.8Hz,1H),7.26(dd,J＝8.5,1.8Hz,1H),7.22(d,J＝1.6Hz,1H),6.78–6.74(m,1H),6.42(s,1H),6.40(d,J＝8.5Hz,1H),4.15–3.96(m,2H),3.64(d,J＝16.4Hz,1H),3.54(d,J＝16.4Hz,1H),3.46(s,3H),2.53(s,3H),1.17(t,J＝7.2Hz,3H).13CNMR(150MHz,CDCl3)δ＝169.1(Cq),161.1(Cq),158.7(Cq),147.9(CH),145.7(Cq),139.7(Cq),137.7(CH),136.8(Cq),128.2(CH),124.4(CH),123.0(Cq),120.7(CH),115.8(CH),107.1(CH),106.9(CH),61.3(CH2),38.7(CH2),38.4(CH3),14.8(CH3),14.1(CH3).HR-MS(ESI)m/z calcd for C21H23N4O4[M+H+]395.1714,found 395.1711.
由上可知，其为乙基-2-{6-乙酰胺基-2-[甲基(2-吡啶基)胺基]-1-氧-1,2-二氢异喹啉-3-基}乙酰酯，结构式为：
Figure BDA0002269964180000301
(31)3ae：1H NMR(600MHz,CDCl3)δ＝8.31(d,J＝7.9Hz,1H),8.25–8.22(m,1H),7.67–7.62(m,1H),7.49(d,J＝8.0Hz,1H),7.44–7.40(m,1H),7.40–7.36(m,1H),7.27(t,J＝7.4Hz,2H),7.23–7.17(m,3H),6.74–6.70(m,1H),6.39(s,1H),6.23(d,J＝8.4Hz,1H),3.91(s,2H),3.15(s,3H).13C NMR(150MHz,CDCl3)δ＝161.6(Cq),158.7(Cq),148.0(CH),144.9(Cq),137.7(CH),137.0(Cq),136.6(Cq),132.9(CH),129.1(CH),128.5(CH),128.0(CH),126.8(CH),126.3(CH),125.9(Cq),125.8(CH),115.1(CH),106.4(CH),106.2(CH),38.8(CH2),37.8(CH3).HR-MS(ESI)m/z calcd for C22H20N3O[M+H+]342.1601,found342.1594.
由上可知，其为3-苄基-2-[甲基(2-吡啶基)胺基]异喹啉-1(2氢)-酮，结构式为：
Figure BDA0002269964180000311
(32)3af：1H NMR(600MHz,CDCl3)δ＝8.32(d,J＝7.9Hz,1H),8.22–8.19(m,1H),7.69–7.65(m,1H),7.53(d,J＝7.9Hz,1H),7.49(d,J＝8.1Hz,2H),7.44(dd,J＝7.6,7.6Hz,1H),7.36–7.32(m,1H),7.30(d,J＝8.0Hz,2H),6.71(dd,J＝7.1,5.0Hz,1H),6.44(s,1H),6.16(d,J＝8.4Hz,1H),3.97(s,2H),3.19(s,3H).13C NMR(150MHz,CDCl3)δ＝161.5(Cq),158.5(Cq),147.9(CH),143.9(Cq),141.2(Cq),137.7(CH),136.4(Cq),133.0(CH),129.4(CH),129.1(q,2JC-F＝32.6Hz,Cq),128.1(CH),126.6(CH),126.0(Cq),125.9(CH),125.4(q,3JC-F＝3.0Hz,CH),124.0(q,1JC-F＝271.8Hz,Cq),115.3(CH),106.7(CH),106.2(CH),38.8,37.9(CH3).19F NMR NMR(565MHz,CDCl3)δ＝-62.31(s).HR-MS(ESI)m/z calcd forC23H19F3N3O[M+H+]410.1475,found 410.1465.
由上可知，其为2-[甲基(2-吡啶基)胺基]-3-[4-(三氟甲基)苄基]异喹啉-1(2氢)-酮，结构式为：
Figure BDA0002269964180000312
(33)4ae：1H NMR(600MHz,CDCl3)δ＝11.06(s,1H),8.40–8.36(m,1H),7.61(ddd,J＝8.2,7.1,1.3Hz,1H),7.47–7.41(m,2H),7.38–7.34(m,2H),7.31–7.29(m,2H),7.26–7.22(m,1H),6.28(s,1H),3.97(s,2H).13C NMR(150MHz,CDCl3)δ＝164.5(Cq),140.6(Cq),138.4(Cq),136.6(Cq),132.6(CH),129.3(CH),128.8(CH),127.3(CH),127.1(CH),126.0(CH),125.8(CH),124.5(Cq),104.9(CH),39.5(CH2).HR-MS(ESI)m/z calcd for C16H14NO[M+H+]236.1070,found 236.1065.
由上可知，其为3-苄基异喹啉-1(2氢)-酮，结构式为
(34)4ag’：1H NMR(600MHz,CDCl3)δ＝8.08(dd,J＝7.7,1.2Hz,1H),7.80(s,1H),7.49(dd,J＝7.5,1.4Hz,1H),7.34(dd,J＝7.6,1.1Hz,1H),7.24(d,J＝7.3Hz,1H),5.16(dd,J＝10.1,7.6Hz,1H),4.03–3.96(m,1H),2.24–2.19(m,1H),2.16–2.09(dtd,J＝12.9,10.3,2.5Hz,1H),1.87–1.80(m,1H),1.77–1.69(m,3H),1.62–1.51(m,5H),1.40–1.37(m,1H).13C NMR(150MHz,CDCl3)δ＝163.6(Cq),143.7(Cq),134.4(Cq),132.7(CH),127.9(CH),126.8(CH),126.7(CH),126.3(Cq),111.5(CH),39.0(CH),37.5(CH2),26.3(CH2),26.2(CH2),25.5(CH2),24.6(CH2),23.5(CH2).HR-MS(ESI)m/z calcd for C16H20NO[M+H+]242.1539,found 242.1532.
由上可知，其为(S,E)-6,8,9,10,11,12,13,13a-8氢-5氢-环壬烷[c]异喹啉-5-酮，结构式为：
(35)4ag：1H NMR(600MHz,CDCl3)δ＝10.89(sbr,1H),8.47(d,J＝7.9Hz,1H),7.79–7.57(m,2H),7.47–7.43(m,1H),2.91–2.87(m,2H),2.85–2.81(m,2H),1.85(p,J＝8.1Hz,2H),1.78–1.73(m,2H),1.47(ddq,J＝23.5,11.9,4.9Hz,4H),1.37(p,J＝6.3Hz,2H).13CNMR(150MHz,D6-DMSO,100℃)δ＝162.4(Cq),139.6(Cq),138.2(Cq),132.6(CH),127.5(CH),126.0(Cq),125.5(CH),123.6(CH),111.9(Cq),29.5(CH2),27.0(CH2),26.5(CH2),26.2(CH2),24.8(CH2),24.8(CH2),24.7(CH2).HR-MS(ESI)m/z calcd for C16H20NO[M+H+]242.1539,found 242.1527.
由上可知，其为6,7,8,9,10,11,12,13-八氢-5氢-环壬[c]异喹啉-5-酮，结构式为：
Figure BDA0002269964180000331
以上所述仅为本发明的实施例，并非因此限制本发明的专利范围，凡是利用本发明说明书内容所作的等效结构或等效流程变换，或直接或间接运用在其他相关的技术领域，均同理包括在本发明的专利保护范围内。

Claims (10)

1.一种多取代异喹啉-1(2氢)-酮衍生物，其特征在于，具有如式(Ⅰ)所示结构：
Figure FDA0002269964170000011
所述衍生物包括其立体异构体、溶剂化物、水合物或药学上可接受的盐或共晶；L4为N-甲基-N-2-吡啶基或氢。
2.根据权利要求1所述多取代异喹啉-1(2氢)-酮衍生物，其特征在于，当L4为N-甲基-N-2-吡啶基时，L1选自以下一种或多种基团：氢、卤素、C1-C6烷基、三氟甲基、C1-C6烷氧基、取代或未取代的苯基、腈基、酯基、甲硫基、取代或未取代的乙酰基；L2选自以下一种或多种基团：氢、取代或未取代的C1-C7烷基；L3选自以下一种或多种基团：取代或未取代的C1-C7烷基、取代或未取代的苄基、取代或未取代的二苯基磷酰甲基、乙酰酯基；
当L4为氢时，L1选自以下一种或多种基团：氢、C1-C6烷基、C1-C6烷氧基、取代或未取代的苯基、甲硫基；L2选自以下一种或多种基团：氢、取代或未取代的C1-C7烷基；L3选自以下一种或多种基团：取代或未取代的C1-C7烷基、取代或未取代的苄基。
3.一种如权利要求1-2任一所述多取代异喹啉-1(2氢)-酮衍生物的制备方法，其特征在于，当L4为N-甲基-N-2-吡啶基时，包括以下步骤：
将N'-甲基-N'-(2-吡啶基)苯甲酰肼和联烯、添加剂混合后，在氩气保护下，在混合物中加入催化剂、溶剂，在恒定电流模式下以非分隔式电解池进行反应，并浓缩、柱层析分离得到产物；进一步地，所述非分隔式电解池的阳极为网状玻璃态碳电极(RVC)，阴极为铂片电极；更进一步地，所述阳极规格为1.0×1.5厘米，所述阴极规格为1.0×1.0厘米；更进一步地，所述恒定电流模式下，恒定电流为2.0～10.0mA，优选为2.0mA；所述反应温度为23～80℃，优选为40℃；反应时间为8-15h，优选为15h。
4.根据权利要求3所述多取代异喹啉-1(2氢)-酮衍生物的制备方法，其特征在于，所述N'-甲基-N'-(2-吡啶基)苯甲酰肼化合物与联烯的摩尔比为0.1-1.0：0.1-1.0；优选为0.55：0.50；所述催化剂与混合物的摩尔比为0.05～0.2，优选为0.1；所述添加剂与联烯的摩尔比为1.0～2.0，优选为2.0；所述溶剂为三氟乙醇，更进一步地，所述三氟乙醇用量为3-4体积份，优选为3.5体积份。
5.根据权利要求3所述多取代异喹啉-1(2氢)-酮衍生物的制备方法，其特征在于，所述催化剂为醋酸钴、醋酸钴的水合物或其它含钴元素的催化剂。
6.根据权利要求3所述多取代异喹啉-1(2氢)-酮衍生物的制备方法，其特征在于，所述添加剂为NaOAc、NaOPiv、PivOH、KOAc或KOPiv，优选为NaOAc；所述溶剂为MeOH、EtOH、HFIP、toluene、TFE，优选为TFE。
7.根据权利要求3所述多取代异喹啉-1(2氢)-酮衍生物的制备方法，其特征在于，所述柱层析中的层析液为石油醚、乙酸乙酯和/或三乙胺；进一步地，所述三种层析液的体积比为0:100:1～200:100:0.33。
8.根据权利要求3所述多取代异喹啉-1(2氢)-酮衍生物的制备方法，其特征在于，当L4为氢时，包括以下步骤：
将3-[(二苯基磷酰)甲基]-2-[甲基(2-吡啶基)胺基]异喹啉-1(2氢)-酮衍生物、碘化钾、n-Bu4NPF6置于反应容器中，安装电极，其中阳极为金属镁，阴极为铂片，在保护气体氛围下加入溶剂DMF，再加入SmI2的四氢呋喃溶液，在恒定电流下以非分隔式电解池模式反应；反应结束后，依次用EtOAc稀释，饱和食盐水洗涤，有机相干燥，过滤蒸干，硅胶柱层析纯化得产物；进一步地，所述恒定电流为5.0mA；进一步地，所述反应温度为室温，反应时间为10h。
9.根据权利要求8所述多取代异喹啉-1(2氢)-酮衍生物的制备方法，其特征在于，所述3-[(二苯基磷酰)甲基]-2-[甲基(2-吡啶基)胺基]异喹啉-1(2氢)-酮衍生物、碘化钾、n-Bu4NPF6的摩尔比为1:2:2；所述SmI2的四氢呋喃溶液浓度为0.1mmol/mL，用量为10mol％；进一步地，所述溶剂为DMF，其用量为5.0mL。
10.根据权利要求9所述多取代异喹啉-1(2氢)-酮衍生物的制备方法，其特征在于，所述硅胶柱层析纯化所用洗脱剂为体积比1:1的乙酸乙酯：石油醚。
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