CN116239624A - 一类基于β-异靛蓝骨架近红外氟硼染料及其制备方法和应用 - Google Patents

一类基于β-异靛蓝骨架近红外氟硼染料及其制备方法和应用 Download PDF

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CN116239624A
CN116239624A CN202211650665.8A CN202211650665A CN116239624A CN 116239624 A CN116239624 A CN 116239624A CN 202211650665 A CN202211650665 A CN 202211650665A CN 116239624 A CN116239624 A CN 116239624A
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卢华
王思斯
肖遥
徐永强
盖立志
陈紫薇
于春艳
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Abstract

本发明公开了一类基于β‑异靛蓝骨架近红外氟硼染料及其制备方法和应用。所述的氟硼染料具有式A‑D任一项所示结构，具有优异的光物理性质，如近红外吸收和发射、高的摩尔吸光系数、较高的发光效率以及优异的光稳定性，在生物成像与光诊疗等领域有着潜在的应用价值。其制备方法可以很容易地通过商业化的邻苯二甲腈的三步反应来实现，具有原料易得、底物适用性强、后处理简单、对设备要求低和易于工业生产化等优点。
Figure DDA0004010424730000011

Description

一类基于β-异靛蓝骨架近红外氟硼染料及其制备方法和应用
技术领域
本发明涉及有机化学领域，具体涉及一类基于β-异靛蓝骨架近红外氟硼染料及其制备方法和应用。
背景技术
氟硼类染料，以氟硼二吡咯亚甲基(BODIPY)为典型代表，具有优异的光物理性质，如光稳定性好、可修饰性强、摩尔消光系数高以及发光强等，在分子识别、生物成像、光诊疗以及太阳能电池及等领域显现出巨大的应用价值(Curr.Med.Chem.,2017,24,2745；Chem.Commun.,2019,55,8722)。近红外具有更深的组织穿透性，更少的光信号衰减以及更低的动物背景自发荧光干扰。然而，氟硼类母核的发光在绿光区域，需要结构修饰才能获得红光区染料(Chem.Soc.Rev.,2014,43,4778-4823)。目前，近红外染料母核的缺乏限制了染料在复杂生物体系中的应用。
近期，以吡咯并吡咯(DPP)和异靛蓝(IID)为骨架发展了一类新型近红外染料，该类染料母核具有近红外吸收和发光、高摩尔吸光度等优点，已应用于生物成像、分子识别、多模式生物诊疗和太阳能电池等领域(DyesPigments,2022,198,110040)。尽管异吲哚单元是很多染料和功能材料的重要组成骨架(Adv.Opt.Mater.,2022,10,2102514)，但作为异吲哚家族的异构体，β-异靛蓝作为功能骨架的研究却很少报道。
本发明通过二亚氨基β-异靛蓝与氨基氮杂环化合物或亚甲基氰基氮杂环化合物缩合反应获得四齿配体，随后和硼配位获得一类基于β-异靛蓝骨架的近红外氟硼染料。光物理性质研究表明，此类化合物的具有近红外吸收和发光、优异的光稳定性、高摩尔吸光度和较高的荧光量子产率，使其在生物成像与光诊疗等领域具有潜在的应用。同时B-O-B桥联刚性结构使这类化合物具有光学活性，进而获得了一类近红外圆偏振发光染料。
发明内容
本发明的一个目的是提供一类基于β-异靛蓝骨架近红外氟硼染料，这是一类全新的母核结构，具有较大的π共轭骨架，B-O-B桥联使结构刚性。
一类基于β-异靛蓝骨架近红外氟硼染料，其结构如下式之一：
Figure BDA0004010424710000021
其中，R1和R2各自独立地选自H、C1-C20的烷基、C3-C6的环烷基、芳香基团、卤素、烯丙基、三甲基硅烷、三氟甲基、硝基、-S-R3、-O-R3；其中，R3选自H、C1-C20的烷基、C3-C6的环烷基、芳香基团；
Figure BDA0004010424710000022
表示含氮杂环，含氮杂环选自五元、六元氮杂环或者苯并氮杂环中的一种。
进一步地，卤素选自F，Cl，Br或I中的一种；芳香基团选自苯环、噻吩环、呋喃环、咪唑环及其衍生物中的一；
Figure BDA0004010424710000023
为咪唑、噻唑、噁唑、吡啶、嘧啶、喹啉或异喹啉中的一种。
本发明的另一个目的是提供了上述一类基于β-异靛蓝骨架近红外氟硼染料的制备方法，通过商业化的邻苯二甲腈的三步反应来实现，底物适用性强，后处理简单，并高产率地得到一种含有β-异靛蓝功能骨架的新型染料。所制备得到的β-异靛蓝染料具有高摩尔吸光系数和较高的近红外发光强度，使得其在生物成像与光诊疗等领域有着潜在的应用。
本发明是通过以下技术方案实现的：
步骤(1)、氩气环境下加热金属钠和第一溶剂，待金属钠全部溶解后加入式VI所示的邻苯二甲腈进行反应，产物纯化后得到中间体二亚氨基β-异靛蓝V；
Figure BDA0004010424710000024
步骤(2)、将步骤(1)所得中间体二亚氨基β-异靛蓝V与2-氨基氮杂环III或2-氮杂环乙腈IV加入第二溶剂中反应，产物纯化后分别得到中间体I或II；
Figure BDA0004010424710000031
步骤(3)、将步骤(2)所得中间体I或II溶解于第三溶剂，加入碱和三氟化硼乙醚进行反应，产物纯化后得到最终产物A～D；
Figure BDA0004010424710000032
作为优选，步骤(1)中，邻苯二甲腈VI和金属钠的摩尔比为1:(1.05～1.20)；
作为优选，步骤(2)中，β-异靛蓝V与2-氨基杂环III或2-杂环乙腈IV的摩尔比为1：(4～5)；
作为优选，步骤(3)中，中间体I或II、碱和三氟化硼乙醚的摩尔比为1：(1～10)：(2～20)；
作为优选，第一溶剂为1-十二烷硫醇，第二溶剂和第三溶剂各自独立地选自二氯甲烷、氯仿、甲苯、乙腈、四氢呋喃、二甲基亚砜、N,N-二甲基甲酰胺、乙酸乙酯、氯苯、邻/间/对二氯苯、1,4-二氧六环中的一种或两种以上混合；
作为优选，所述碱包括有机碱和无机碱，其中有机碱为三乙胺、N,N-二异丙基乙胺、1,8-二氮杂双环[5.4.0]十一碳-7-烯、吡啶、1,5-二氮杂双环[4.3.0]壬-5-烯和三乙烯二胺中的一种或几种混合；无机碱为碳酸钠、碳酸氢钠、碳酸钾、碳酸氢钾、氢氧化钠和氢氧化钾中的一种或几种混合。
作为优选，步骤(1)的反应温度为100～200℃，反应时间为2～10h；步骤(2)的反应温度为150～200℃，反应时间为5～24h；步骤(3)的反应温度110～150℃，反应时间为1～5h。
作为优选，上述化合物纯化方法采用柱层析、重结晶纯化粗产品，所述柱层析洗脱液为乙酸乙酯与石油醚的混合液或乙酸乙酯与二氯甲烷的混合液中的一种，体积比为1：2～50。
本发明的再一个目的是提供上述基于β-异靛蓝骨架近红外氟硼染料在生物成像与光疗领域的应用。
与现有技术相比，本发明具有以下有益效果：
本发明提供了一类β-异靛蓝骨架近红外氟硼染料及其制备方法，该方法可以很容易地通过商业化邻苯二甲腈的三步反应来实现，具有产物收率高、底物适用性强和后处理简单等优点。此外，所制备的β-异靛蓝染料具有高摩尔吸光系数和较高的近红外发光强度，使得其在生物成像与光诊疗等领域有着可观的应用价值。
附图说明
附图是用以进一步解释本发明的具体实施案例，并不构成对本发明的限制。在附图中：
图1是本发明合成β-异靛蓝骨架近红外氟硼染料的示意图。
图2是实施例中制得的部分β-异靛蓝骨架近红外氟硼染料在二氯甲烷中的吸收图谱；其中A为实施例1、3、5、7所得近红外氟硼染料的吸收图谱，B为实施例4、6所得近红外氟硼染料的吸收图谱。
图3是实施例中制得的部分β-异靛蓝骨架近红外氟硼染料在二氯甲烷中的发射图谱；其中A为实施例1、3、5、7所得近红外氟硼染料的发射图谱，B为实施例4、6所得近红外氟硼染料的发射图谱。
图4是实施例中制得的部分β-异靛蓝骨架近红外氟硼染料在二氯甲烷中的光稳定性测试图谱。其中A为实施例1、3、5、7所得近红外氟硼染料的光稳定性测试图谱，B为实施例4、6所得近红外氟硼染料的光稳定性测试图谱。
具体实施方案
以下将通过具体实施例，对本发明作进一步的详细说明。
实施例1
Figure BDA0004010424710000051
(1)取50mL烧瓶，加入金属钠(60mg，2.6mmol)和5mL的1-十二烷硫醇，将反应加热至100℃，待金属钠全部溶解后，在氩气环境下加入4，5-双(4-叔丁基苯基)邻苯二甲腈(VI-1，980mg，2.5mmol)反应1小时后，将反应温度升至180℃后继续反应1小时。反应结束后，用过量的石油醚淬灭反应，过滤收集粗产物。将粗产物经柱层析(洗脱剂为乙酸乙酯/石油醚＝1/4)和重结晶得中间体V-1(498mg,50％)；(2)取50mL烧瓶，加入中间体V-1(47mg，0.06mmol)、2-氨基吡啶(III，23mg，0.24mmol)和3mL 1-氯萘，加热至200℃后反应8小时。溶液颜色从淡黄色逐渐变为紫色。反应结束后，将粗产物经柱层析(洗脱剂：乙酸乙酯/二氯甲烷＝1/50)重结晶得中间体I-1(26mg,47％)；(3)取50mL的烧瓶，室温下加入中间体I-1(120mg,0.127mmol)和12mL甲苯，待中间体I-1完全溶解后加入0.72mL三乙胺反应10分钟，再缓慢滴加0.96mL三氟化硼乙醚，最后将温度升高到130℃回流1.5小时。反应结束后，将粗产物通过硅胶柱色谱法纯化(洗脱剂：乙酸乙酯/二氯甲烷＝1:50)，重结晶后得到产物A-1(36mg，28％)、B-1(56mg，44％)。
A-1：1H NMR(500MHz,CDCl3)δ8.91(d,J＝1.6Hz,1H),8.90–8.89(m,1H),7.94(s,2H),7.85(d,J＝8.0Hz,4H),7.84–7.76(m,4H),7.54(d,J＝1.3Hz,2H),7.53(q,J＝1.3Hz,4H),7.51(d,J＝1.2Hz,2H),7.35(d,J＝1.3Hz,4H),7.34(s,4H),1.34(s,36H).13C NMR(125MHz,CDCl3)δ157.50,155.22,152.52,152.48,152.44,142.35,138.48,138.44,137.76,137.23,136.81,136.32,135.13,135.08,135.02,129.06,129.04,129.02,129.00,128.97,126.98,126.95,126.91,126.06,126.03,126.00,125.97,125.93,125.89,125.85,125.81,124.87,124.27,124.06,34.94,34.93,31.27,31.26,31.24,31.21.HRMS-ESI:calcd[C66H64B2F4N6+H]+1039.5315；found 1039.5346.
B-1：1H NMR(400MHz,CD2Cl2)δ8.67(d,J＝5.6Hz,4H),8.13(s,2H),7.96–7.92(m,2H),7.45(d,J＝8.4Hz,2H),7.28(d,J＝8.4Hz,4H),7.24(t,J＝6.0Hz,2H),7.19(t,J＝8.0Hz,8H),7.01(d,J＝8.0Hz,4H),1.31(d,J＝4.0Hz,36H).13C NMR(126MHz,CD2Cl2)δ158.99,155.46,150.51,144.67,142.39,141.93,139.39,138.70,138.10,135.09,133.04,129.85,129.54,127.15,125.56,125.29,125.26，124.11,118.34,34.80,31.49.HRMS-ESI:calcd[C66H64B2F2N6O+H]+1017.5369；found 1017.5394.
实施例2
Figure BDA0004010424710000071
按照实施例1的制备方法进行制备，不同的是，将步骤(2)中的2-氨基吡啶III-1替换成等当量的2-吡啶乙腈IV-1，制得到最终产物C-1(48mg，35％)、D-1(63mg，47％)。
C-1：1H NMR(500MHz,CDCl3)δ9.11(d,J＝1.2Hz,1H),9.10(d,J＝1.2Hz,1H),8.28(td,J＝7.7,1.1Hz,2H),7.93(s,2H),7.81–7.77(m,4H),7.61–7.58(m,4H),7.53–7.50(m,6H),7.36–7.33(m,8H),1.34(s,36H).13C NMR(125MHz,CDCl3)δ152.52,152.48,152.44,148.02,142.47,142.19,138.01,137.96,137.92,137.76,136.70,135.07,134.39,132.61,130.69,129.06,129.04,129.02,129.00,128.98,127.91,127.36,125.97,125.93,125.89,125.85,125.81,125.14,122.00,111.95,91.88,34.94,34.93,31.26,31.26,31.25,31.24,31.21.HRMS-ESI:calcd[C70H64B2F4N6+H]+1087.5315；found 1087.5321.
D-1：1H NMR(500MHz,CDCl3)δ9.27–9.25(m,1H),9.25(d,J＝1.5Hz,1H),8.28(td,J＝7.8,1.2Hz,2H),7.91(s,2H),7.78(s,2H),7.60(d,J＝1.3Hz,2H),7.59(d,J＝1.3Hz,2H),7.53(d,J＝1.3Hz,2H),7.51(d,J＝1.2Hz,2H),7.35–7.33(m,10H),7.33–7.30(m,2H),1.34(s,36H).13C NMR(125MHz,CDCl3)δ152.52,152.48,152.44,152.31,152.26,149.35,149.30,142.40,138.01,137.96,137.92,137.76,137.73,137.67,136.89,133.13,133.10,131.66,131.63,129.06,129.04,129.02,129.00,128.98,128.33,128.30,128.12,128.09,125.97,125.93,125.89,125.85,125.81,125.12,122.24,111.95,91.06,91.03,34.94,34.93,31.27,31.26,31.24,31.21.HRMS-ESI:calcd[C70H64B2F2N6O+H]+1065.5296；found1065.5292.
实施例3
Figure BDA0004010424710000081
按照实施例1的制备方法进行制备，不同的是，将步骤(1)中VI-1替换成等当量的VI-2，制得到最终产物A-2(18mg，12％)、B-2(23mg，16％)。
A-2：1H NMR(500MHz,CDCl3)δ8.91(d,J＝1.6Hz,1H),8.90–8.89(m,1H),7.87(s,2H),7.85(dd,J＝7.8,1.7Hz,2H),7.84–7.76(m,4H),7.58(s,2H),7.28(s,16H),1.34(s,36H).3C NMR(125MHz,CDCl3)δ157.50,155.69,149.99,149.95,149.91,142.35,137.60,136.39,135.13,135.08,135.02,134.89,134.86,133.54,131.57,131.55,131.52,131.50,131.47,126.98,126.95,126.92,126.91,126.90,126.88,126.86,126.06,126.03,126.00,125.43,124.10,123.10,34.46,34.45,31.27,31.25,31.24,31.21.HRMS-ESI:calcd[C66H64B2F4N6S4+H]+1167.4198；found 1167.4210.
B-2：1H NMR(400MHz,CD2Cl2)δ8.54(dd,J＝6.1,1.1Hz,2H),7.89–7.84(m,4H),7.54–7.51(m,6H),7.47–7.45(m,4H),7.41–7.37(m,8H),7.29(d,J＝8.0Hz,2H),7.20–7.16(dd,J＝9.7,3.5Hz,2H),1.39(s,18H),1.26(s,18H).13CNMR(126MHz,CD2Cl2)δ157.9,155.0,152.8,152.1,142.0,141.8,140.4,139.3,133.9,133.7,132.8,132.5,129.7,129.3,128.7,127.4,127.3,126.1,124.0,123.5,118.5,35.1,34.9,31.4.HRMS-ESI:calcd[C66H64B2F2N6OS4+H]+1145.4251；found 1145.4250.
实施例4
Figure BDA0004010424710000091
按照实施例3的制备方法进行制备，不同的是，将步骤(2)中的2-氨基吡啶III-1替换成等当量的2-吡啶乙腈IV-1，制得到最终产物C-2(24mg，16％)、D-2(52mg，35％)。
C-2：1H NMR(500MHz,CDCl3)δ9.10(dd,J＝7.3,1.2Hz,2H),8.38(s,2H),8.28(t,J＝7.7,1.1Hz,2H),8.18(s,2H),7.79(t,J＝7.5,1.4Hz,2H),7.51(dd,J＝8.0,1.6Hz,2H),7.28(s,16H),1.34(s,36H).13C NMR(125MHz,CDCl3)δ149.99,149.95,149.91,148.02,142.47,142.43,137.24,136.52,135.24,134.96,134.92,134.88,134.39,131.57,131.55,131.52,131.50,131.47,130.75,130.69,127.36,126.95,126.92,126.90,126.88,126.86,126.33,125.09,123.61,111.95,98.89,34.46,34.45,31.27,31.26,31.25,31.24,31.21.HRMS-ESI:calcd[C70H64B2F4N6S4+H]+1215.4205；found 1215.4198.
D-2：1HNMR(400MHz,CDCl3)δ8.64(d,J＝8.0Hz,2H),8.08(s,2H),7.93–7.84(m,2H),7.77(s,2H),7.67(d,J＝8.0Hz,2H),7.58–7.47(m,8H),7.43(d,J＝8.0Hz,4H),7.38(d,J＝8.0Hz,4H),7.24-7.21(m,2H),1.38(s,18H),1.28(s,18H).13C NMR(126MHz,CDCl3)δ152.8,152.2,150.9,149.8,142.1,140.7,140.6,140.1,134.1,133.2,133.1,130.8,130.3,128.4,127.6,127.4,127.0,125.0,123.3,123.2,121.5,119.2,117.3,74.0,34.9,34.8,31.4.HRMS-ESI:calcd[C70H64B2F2N6OS4+H]+1193.4151；found 1193.4179.
实施例5
Figure BDA0004010424710000101
按照实施例1的制备方法进行制备，不同的是，将步骤(2)中的2-氨基吡啶III-1替换成等当量的2-氨基喹啉III-2，制得到最终产物A-3(26mg，18％)、B-3(35mg，25％)。
A-3：1H NMR(500MHz,CDCl3)δ9.29(d,J＝2.0Hz,2H),8.21(tt,J＝7.9,1.1Hz,4H),8.11–8.09(m,2H),7.94(s,2H),7.86(s,2H),7.81(s,2H),7.73–7.69(m,2H),7.54(d,J＝1.3Hz,2H),7.53(q,J＝1.3Hz,4H),7.51(d,J＝1.2Hz,2H),7.37–7.32(m,8H),1.34(s,36H).13C NMR(125MHz,CDCl3)δ155.24,152.52,152.48,152.44,146.43,140.32,139.58,139.53,139.47,138.48,138.44,137.76,137.23,136.81,136.32,130.13,129.69,129.06,129.04,129.02,129.00,128.97,128.43,127.04,125.97,125.93,125.89,125.85,125.81,124.87,124.31,124.06,117.84,117.81,117.78,34.94,34.93,31.27,31.26,31.24,31.21.HRMS-ESI:calcd[C74H68B2F4N6+H]+1139.5628；found 1139.5614.
B-3：1H NMR(400MHz,CD2Cl2)δ8.83(d,J＝8.0Hz,2H),8.65(s,2H),8.17(m,4H),7.71(d,J＝8.0Hz,2H),7.40(d,J＝8.0Hz,2H),7.30(t,J＝8.0Hz,6H),7.24-7.19(m,8H),7.06(d,J＝8.0Hz,4H),7.02-6.98(m,2H),1.32(s,18H),1.33(s,18H).13C NMR(126MHz,CD2Cl2)δ159.1,156.8,150.6,150.6,145.0,142.6,141.7,140.2,138.7,138.1,135.0,132.7,130.9,129.9,128.2,127.0,126.6,125.8,125.7,125.3,125.0,124.0,34.8,34.8,31.5,31.4.HRMS-ESI:calcd[C74H68B2F2N6O+H]+1117.5682；found 1117.5714.
实施例6
Figure BDA0004010424710000111
按照实施例5的制备方法进行制备，不同的是将步骤(2)中的2-氨基吡啶III-1替换成等当量的2-喹啉乙腈IV-2，制得到最终产物C-3(37mg，25％)、D-3(47mg，32％)。
C-3：1H NMR(500MHz,CDCl3)δ8.43–8.38(m,2H),8.12–8.07(m,2H),7.93(s,2H),7.86–7.79(m,4H),7.66–7.62(m,2H),7.62–7.56(m,4H),7.55–7.46(m,8H),7.37–7.31(m,8H),1.34(s,36H).13C NMR(125MHz,CDCl3)δ169.56,152.52,152.48,152.44,143.87,142.60,138.67,138.01,137.96,137.92,137.76,136.70,135.38,132.63,130.77,129.29,129.06,129.03,129.02,129.00,128.98,127.92,127.82,125.97,125.93,125.89,125.85,125.81,125.14,122.09,122.00,121.27,111.95,100.39,34.94,34.93,31.26,31.26,31.25,31.24,31.21.HRMS-ESI:calcd[C74H68B2F4N6+H]+1187.5628；found 1187.5614.
D-3：1H NMR(400MHz,CDCl3)δ8.64(d,J＝8.0Hz,2H),8.11(s,2H),8.04(d,J＝8.0Hz,2H),7.76(s,2H),7.68(d,J＝12.0Hz,2H),7.58–7.55(m,2H),7.52–7.47(m,8H),7.43–7.38(m,8H),7.13–7.09(m,2H),6.83–6.79(m,2H),1.39(s,18H),1.28(s,18H).13CNMR(126MHz,CDCl3)δ152.8,152.1,151.1,150.8,142.4,140.6,140.3,134.0,133.2,132.9,131.8,131.0,130.6,128.4,128.1,127.7,127.4,127.1,126.4,126.1,124.8,124.7,123.8,119.6,117.9,76.2,34.9,34.8,31.4.HRMS-ESI:calcd[C78H68B2F2N6O+H]+1165.5609；found 1165.5619.
实施例7
Figure BDA0004010424710000121
按照实施例3的制备方法进行制备，不同的是，将步骤(2)中的2-氨基吡啶III-1替换成等当量的2-氨基喹啉III-2，制得到最终产物A-4(25mg，16％)、B-4(51mg，33％)。
A-4：1H NMR(500MHz,CDCl3)δ9.29(d,J＝1.9Hz,2H),8.25–8.17(m,4H),8.12–8.08(m,2H),7.87(s,2H),7.81(ddd,J＝8.2,6.7,1.2Hz,2H),7.71(ddt,J＝7.8,6.9,0.7Hz,2H),7.58(s,2H),7.28(s,16H),1.34(s,36H).13C NMR(125MHz,CDCl3)δ155.09,149.99,149.95,149.91,146.43,140.32,139.58,139.53,139.47,137.60,136.39,134.89,134.86,133.54,131.57,131.55,131.52,131.50,131.47,130.13,129.69,129.02,128.43,127.04,126.95,126.92,126.90,126.88,126.86,125.43,124.10,123.10,117.84,117.81,117.78,34.46,34.45,31.27,31.25,31.24,31.21.HRMS-ESI:calcd[C74H68B2F4N6S4+H]+1267.4511；found 1267.4526.
B-4：1H NMR(400MHz,CD2Cl2)δ8.69(d,J＝8.0Hz,2H),8.09(d,J＝8.0Hz,2H),7.83(s,2H),7.66–7.64(m,2H),7.57–7.52(m,6H),7.47(m,J＝8.0Hz,4H),7.44–7.40(m,8H),7.24–7.21(m,4H),6.95–6.93(m,2H),1.40(s,18H),1.27(s,18H).13C NMR(126MHz,CD2Cl2)δ158.1,156.4,152.8,152.2,141.9,141.8,141.0,140.1,133.9,133.6,132.6,132.4,130.9,130.1,129.5,129.3,128.2,127.4,127.4,126.5,125.8,125.8,124.9,123.8,35.1,35.0,31.4,31.4.HRMS-ESI:calcd[C74H68B2F2N6OS4+H]+1245.4564；found 1245.4596.
实施例8
Figure BDA0004010424710000131
按照实施例7的制备方法进行制备，不同的是，将步骤(2)中的2-氨基吡啶III-1替换成等当量的2-喹啉乙腈IV-2，制得到最终产物C-4(20mg，12％)、D-4(58mg，36％)。
C-4：1H NMR(500MHz,CDCl3)δ9.29(d,J＝1.9Hz,2H),8.25–8.17(m,4H),8.12–8.08(m,2H),7.87(s,2H),7.81(ddd,J＝8.2,6.7,1.2Hz,2H),7.71(ddt,J＝7.8,6.9,0.7Hz,2H),7.58(s,2H),7.28(s,16H),1.34(s,36H).13C NMR(125MHz,CDCl3)δ155.09,149.99,149.95,149.91,146.43,140.32,139.58,139.53,139.47,137.60,136.39,134.89,134.86,133.54,131.57,131.55,131.52,131.50,131.47,130.13,129.69,129.02,128.43,127.04,126.95,126.92,126.90,126.88,126.86,125.43,124.10,123.10,117.84,117.81,117.78,34.46,34.45,31.27,31.25,31.24,31.21.HRMS-ESI:calcd[C78H68B2F4N6S4+H]+1315.4511；found 1315.4524.
D-4：1H NMR(400MHz,CD2Cl2)δ8.69(d,J＝8.0Hz,2H),8.09(d,J＝8.0Hz,2H),7.83(s,2H),7.66–7.64(m,2H),7.57–7.52(m,6H),7.47(m,J＝8.0Hz,4H),7.44–7.40(m,8H),7.24–7.21(m,4H),6.95–6.93(m,2H),1.40(s,18H),1.27(s,18H).13C NMR(126MHz,CD2Cl2)δ158.1,156.4,152.8,152.2,141.9,141.8,141.0,140.1,133.9,133.6,132.6,132.4,130.9,130.1,129.5,129.3,128.2,127.4,127.4,126.5,125.8,125.8,124.9,123.8,35.1,35.0,31.4,31.4.HRMS-ESI:calcd[C78H68B2F2N6OS4+H]+1293.4492；found 1293.4502.
实施例9
Figure BDA0004010424710000141
按照实施例1的制备方法进行制备，不同的是，将步骤(2)中的2-氨基吡啶III-1替换成等当量的3-甲基-2-氨基喹啉III-3，制得到最终产物A-5(35mg，26％)、B-5(52mg，40％)。
A-5：1H NMR(500MHz,CDCl3)δ7.94(s,2H),7.86(s,2H),7.70(d,J＝1.0Hz,1H),7.68(d,J＝1.3Hz,1H),7.55–7.51(m,10H),7.35(d,J＝1.3Hz,4H),7.34(d,J＝1.4Hz,4H),7.18(dd,J＝1.3,0.7Hz,1H),7.17(t,J＝0.9Hz,1H),2.76(d,J＝0.8Hz,6H),1.34(s,36H).13C NMR(125MHz,CDCl3)δ164.21,155.34,152.52,152.48,152.44,145.32,140.94,138.48,138.44,137.77,137.23,136.81,136.62,136.36,129.06,129.04,129.02,129.00,128.97,128.76,127.86,125.97,125.93,125.89,125.85,125.81,124.87,124.37,124.06,34.94,34.93,31.26,31.26,31.25,31.23,31.21,23.18.HRMS-ESI:calcd[C68H68B2F4N6+H]+1067.5627；found 1067.5646.
B-5：1H NMR(500MHz,CDCl3)δ7.98(s,2H),7.82(s,2H),7.73(d,J＝1.1Hz,1H),7.71(d,J＝1.1Hz,1H),7.55–7.50(m,10H),7.35(d,J＝1.3Hz,4H),7.34(d,J＝1.4Hz,4H),7.05(p,J＝0.8Hz,1H),7.03(dt,J＝1.5,0.8Hz,1H),2.80(d,J＝0.8Hz,6H),1.34(s,36H).13C NMR(125MHz,CDCl3)δ165.79,165.74,154.54,154.48,152.52,152.48,152.44,146.35,146.30,140.85,138.48,138.44,137.76,137.58,137.15,137.12,136.81,129.05,129.04,129.02,129.00,128.97,128.60,128.57,125.97,125.93,125.89,125.85,125.81,124.86,124.70,124.66,124.06,34.94,34.93,31.27,31.26,31.24,31.21,23.34,23.30.HRMS-ESI:calcd[C68H68B2F2N6O+H]+1045.5609；found 1045.5596.
实施例10
Figure BDA0004010424710000151
按照实施例9的制备方法进行制备，不同的是，将步骤(2)中的2-氨基吡啶III-1替换成等当量的6-甲基-2-吡啶乙腈IV-3，制得到最终产物C-5(22mg，16％)、D-5(49mg，36％)
C-5：1H NMR(500MHz,CDCl3)δ8.15–8.08(m,2H),7.93(s,2H),7.80(s,2H),7.62–7.56(m,4H),7.55–7.49(m,4H),7.37–7.32(m,8H),7.28(dd,J＝7.7,1.1Hz,2H),7.13(dt,J＝8.1,0.9Hz,2H),2.71(d,J＝0.8Hz,6H).13C NMR(125MHz,CDCl3)δ171.28,152.52,152.48,152.44,152.09,149.73,141.17,138.01,137.96,137.92,137.76,136.70,135.26,132.63,130.76,129.06,129.04,129.02,129.00,128.98,128.61,127.91,125.97,125.93,125.89,125.85,125.81,125.14,122.00,111.96,101.05,34.94,34.93,31.26,31.26,31.25,31.24,31.21,23.17.HRMS-ESI:calcd[C72H68B2F4N6+H]+1115.5629；found1115.5596.
D-5：1H NMR(500MHz,CDCl3)δ8.12(t,J＝8.0Hz,2H),7.91(s,2H),7.78(s,2H),7.62–7.56(m,4H),7.55–7.49(m,4H),7.37–7.31(m,8H),7.12(dd,J＝7.7,1.1Hz,2H),7.00(dt,J＝8.1,0.9Hz,2H),2.73(d,J＝0.8Hz,6H).13C NMR(125MHz,CDCl3)δ153.41,152.52,152.48,152.44,152.25,150.83,141.00,138.87,138.01,137.96,137.92,137.76,136.89,133.13,131.36,129.30,129.06,129.04,129.02,129.00,128.98,128.31,125.97,125.93,125.89,125.85,125.81,125.12,122.24,111.96,92.98,34.94,34.93,31.26,31.26,31.25,31.24,31.21,23.27.HRMS-ESI:calcd[C72H68B2F2N6O+H]+1093.5609；found1093.5632.
实施例11
Figure BDA0004010424710000161
按照实施例3的制备方法进行制备，不同的是，将2-氨基喹啉III-1替换成等当量的6-甲基-2-氨基吡啶III-3，制得到最终产物A-6(18mg，12％)、B-6(29mg，20％)。
A-6：1H NMR(500MHz,CDCl3)δ7.88(s,2H),7.70(d,J＝1.1Hz,1H),7.68(d,J＝1.3Hz,1H),7.58(s,2H),7.53(t,J＝7.7Hz,2H),7.28(s,16H),7.18(dd,J＝1.3,0.7Hz,1H),7.17(t,J＝0.9Hz,1H),2.76(d,J＝0.7Hz,6H),1.34(s,36H).13C NMR(125MHz,CDCl3)δ164.29,155.46,149.99,149.95,149.91,145.32,140.94,137.60,136.77,136.39,134.89,134.86,133.59,131.57,131.55,131.52,131.50,131.47,128.76,127.86,126.95,126.92,126.90,126.88,126.86,125.52,124.10,123.10,34.46,34.45,31.27,31.26,31.25,31.24,31.21,23.18.HRMS-ESI:calcd[C68H68B2F4N6S4+H]+1195.4511；found 1195.4526.
B-6：1H NMR(400MHz,CDCl3)δ7.75(s,2H),7.66–7.61(m,4H),7.44(d,J＝8.6Hz,4H),7.41–7.34(m,12H),7.12(d,J＝8.2Hz,2H),6.86(d,J＝7.0Hz,2H),2.69(s,6H),1.36(s,18H),1.25(s,18H).13C NMR(126MHz,CDCl3)δ156.40,155.86,153.25,151.69,151.54,140.86,140.58,140.35,134.06,132.79,132.34,132.15,129.79,129.49,128.75,127.01,126.93,125.35,124.30,122.02,120.70,46.23,34.87,34.77,31.43,31.35,22.45,10.05.HRMS-ESI:calcd[C68H68B2F2N6OS4+H]+1173.4492；found 1173.4516.
实施例12
Figure BDA0004010424710000171
按照实施例11的制备方法进行制备，不同的是，将步骤(2)中的6-甲基-2氨基吡啶III-3替换成等当量的6-甲基-2吡啶乙腈IV-3，制得到最终产物C-6(33mg，21％)、D-6(70mg，46％)
C-6：1H NMR(500MHz,CDCl3)δ8.39(s,2H),8.20(s,2H),8.12(s,2H),7.31–7.24(m,18H),7.13(dt,J＝8.0,0.9Hz,2H),2.71(d,J＝0.7Hz,6H),1.34(s,36H).13C NMR(125MHz,CDCl3)δ152.09,149.99,149.95,149.91,149.73,141.44,141.17,137.24,136.52,135.45,134.96,134.92,134.88,131.57,131.55,131.52,131.50,131.47,130.77,130.76,128.61,126.95,126.92,126.90,126.88,126.86,126.33,125.09,123.61,111.96,101.53,34.46,34.45,31.27,31.26,31.25,31.24,31.21,23.17.HRMS-ESI:calcd[C72H68B2F4N6S4+H]+1243.4510；found 1243.4516.
D-6：1H NMR(500MHz,CDCl3)δ8.12(t,J＝8.0Hz,2H),7.16–7.09(m,4H),7.05(s,2H),7.00(dt,J＝8.0,0.9Hz,2H),2.73(d,J＝0.7Hz,6H),1.34(s,36H).13C NMR(125MHz,CDCl3)δ153.41,152.10,150.83,149.99,149.95,149.91,141.00,139.05,137.24,136.53,134.96,134.92,134.88,131.57,131.55,131.52,131.50,131.47,131.36,131.24,129.30,127.18,126.95,126.92,126.90,126.88,126.86,125.19,123.89,111.96,93.47,34.46,34.45,31.27,31.26,31.25,31.24,31.21,23.27.HRMS-ESI:calcd[C72H68B2F2N6OS4+H]+1221.4492；found 1221.4496.
实施例13
Figure BDA0004010424710000181
按照实施例1的制备方法进行制备，不同的是，将步骤(1)中的VI-1替换成等当量的VI-3，将步骤(2)中的2-氨基喹啉III-1替换成等当量的6-甲基-2-氨基吡啶III-3，制得到最终产物A-7(23mg，16％)、B-7(42mg，30％)。
A-7：1HNMR(500MHz,CDCl3)δ7.70(d,J＝1.1Hz,1H),7.68(d,J＝1.3Hz,1H),7.56–7.49(m,4H),7.40(d,J＝1.3Hz,4H),7.38(d,J＝1.4Hz,4H),7.18(dt,J＝1.5,0.7Hz,1H),7.17(t,J＝0.9Hz,1H),7.12(s,2H),6.95(d,J＝1.3Hz,4H),6.94(d,J＝1.2Hz,4H),2.76(d,J＝0.8Hz,6H),1.33(s,36H).13C NMR(125MHz,CDCl3)δ164.31,156.12,156.10,156.07,154.23,147.02,146.21,146.17,146.15,146.13,145.32,140.94,136.58,133.08,128.76,127.87,127.35,127.31,127.28,127.24,127.20,120.25,119.21,119.19,119.17,119.15,119.13,109.95,108.56,33.77,33.75,31.27,31.26,31.25,31.24,31.21,23.18.HRMS-ESI:calcd[C68H68B2F4N6O4+H]+1131.5424；found 1131.5415.
B-7：1H NMR(500MHz,CDCl3)δ7.73(d,J＝1.1Hz,1H),7.71(d,J＝1.3Hz,1H),7.53(t,J＝7.7Hz,2H),7.43(s,2H),7.40(d,J＝1.1Hz,4H),7.38(d,J＝1.4Hz,4H),7.07(s,2H),7.05(t,J＝0.9Hz,1H),7.03(dd,J＝1.4,0.7Hz,1H),6.95(d,J＝1.3Hz,4H),6.94(d,J＝1.2Hz,4H),2.80(d,J＝0.8Hz,6H),1.33(s,36H).13C NMR(125MHz,CDCl3)δ165.79,165.74,156.12,156.10,156.07,153.95,153.90,146.66,146.35,146.30,146.21,146.17,146.15,146.13,140.85,133.10,133.07,129.05,129.02,128.58,128.55,127.35,127.32,127.28,127.24,127.20,121.16,121.13,119.21,119.19,119.17,119.15,119.13,109.78,108.50,33.76,33.75,31.27,31.25,31.24,31.21,23.34,23.30.HRMS-ESI:calcd[C68H68B2F2N6O5+H]+1109.5405；found 1109.5396.
实施例14
Figure BDA0004010424710000201
按照实施例1的制备方法进行制备，不同的是，将步骤(2)中的2-氨基吡啶III-1替换成等当量的2-氨基嘧啶III-4，制得到最终产物A-8(20mg，15％)、B-8(36mg，28％)。
A-8：1HNMR(500MHz,CDCl3)δ8.78(d,J＝1.6Hz,1H),8.77(d,J＝1.8Hz,1H),8.50(dd,J＝3.7,1.7Hz,2H),7.91(d,J＝3.0Hz,4H),7.55–7.50(m,8H),7.36–7.33(m,8H),7.10(dd,J＝6.6,3.8Hz,2H),1.34(s,36H).13C NMR(125MHz,CDCl3)δ160.10,157.76,153.20,152.52,152.48,152.44,143.07,143.02,142.96,138.48,138.44,137.77,137.23,136.73,136.71,129.06,129.04,129.02,129.00,128.97,125.97,125.93,125.89,125.85,125.81,125.41,125.11,124.07,122.08,122.04,122.01,34.94,34.93,31.27,31.26,31.24,31.21.HRMS-ESI:calcd[C64H62B2F4N8+H]+1041.5220；found 1041.5231.
B-8：1H NMR(500MHz,CDCl3)δ8.95(d,J＝1.6Hz,1H),8.93(d,J＝1.8Hz,1H),8.50(dd,J＝3.7,1.7Hz,2H),7.55–7.51(m,8H),7.35(d,J＝1.3Hz,4H),7.34(d,J＝1.4Hz,4H),7.00(dd,J＝5.6,3.8Hz,2H),1.34(s,36H).13C NMR(125MHz,CDCl3)δ161.16,161.11,157.73,153.61,153.55,152.52,152.48,152.44,146.37,146.31,138.48,138.44,137.76,137.58,137.46,137.42,136.71,129.06,129.04,129.02,129.00,128.97,125.97,125.93,125.89,125.85,125.81,125.38,125.22,125.19,124.06,122.45,122.41,34.94,34.93,31.27,31.26,31.24,31.21.HRMS-ESI:calcd[C64H64B2F2N8O+H]+1019.5201；found1019.5291.
实施例15
Figure BDA0004010424710000211
按照实施例1的制备方法进行制备，不同的是，将步骤(1)中的VI-1替换成等当量的VI-4，将步骤(2)中的2-氨基吡啶III-1替换成等当量的2-氨基苯并噻唑III-5，制得到最终产物A-9(11mg，15％)、B-9(34mg，28％)。
A-9：1HNMR(500MHz,CDCl3)δ8.18(d,J＝1.4Hz,1H),8.17(d,J＝1.3Hz,1H),8.07–8.04(m,2H),7.91(d,J＝4.4Hz,4H),7.75(td,J＝7.2,0.8Hz,2H),7.37(td,J＝7.7,1.5Hz,2H),7.26(d,J＝0.8Hz,4H),7.25(s,4H),2.40(s,12H).13CNMR(125MHz,CDCl3)δ159.45,159.39,159.34,153.91,153.24,139.08,139.03,138.97,138.67,138.58,138.53,138.48,137.31,137.29,137.26,136.78,136.70,136.43,136.40,136.37,133.73,133.70,133.67,129.53,129.50,129.47,129.45,129.42,128.71,128.68,128.32,128.28,128.24,128.20,128.16,125.08,125.01,124.92,124.06,123.80,119.27,119.23,119.20,21.24.HRMS-ESI:calcd[C58H40B2F2N6OS2+H]+983.2878.4564；found 983.2896.
B-9：1H NMR(500MHz,CDCl3)δ8.18(d,J＝1.4Hz,1H),8.17(d,J＝1.4Hz,1H),7.97(s,2H),7.87(s,2H),7.75(ddd,J＝8.4,7.6,1.2Hz,4H),7.50(d,J＝1.0Hz,4H),7.48(t,J＝1.2Hz,4H),7.37(td,J＝7.6,1.4Hz,2H),7.26(d,J＝0.8Hz,4H),7.25(d,J＝1.0Hz,4H),2.40(s,12H).13C NMR(125MHz,CDCl3)δ160.72,160.66,159.76,159.70,159.60,159.55,159.43,159.37,151.42,151.39,151.36,151.33,138.58,138.53,138.48,137.67,137.29,137.26,137.11,137.08,136.78,136.70,135.85,135.82,129.53,129.50,129.47,129.45,129.42,128.92,128.50,128.32,128.28,128.24,128.20,128.16,125.36,125.33,125.31,125.28,124.89,124.06,124.05,119.50,119.47,21.24.HRMS-ESI:calcd[C58H40B2F2N6OS2+H]+961.2859；found 961.2878.
实施例16
Figure BDA0004010424710000221
按照实施例1的制备方法进行制备，不同的是，将步骤(1)中的VI-1替换成等当量的VI-6，制得到最终产物A-10(12mg，12％)、B-10(25mg，25％)。
A-10：1H NMR(500MHz,CDCl3)δ8.91(d,J＝1.6Hz,1H),8.90–8.89(m,1H),7.87–7.84(m,2H),7.84–7.77(m,4H),7.54(s,2H),7.39(s,2H).13C NMR(125MHz,CDCl3)δ157.55,157.50,157.44,155.38,155.32,155.26,142.35,137.75,137.71,137.69,137.66,137.63,137.60,137.57,135.44,135.41,135.37,135.13,135.08,135.02,126.98,126.94,126.91,126.31,126.06,126.03,126.00,124.13,124.10,124.06,120.88,119.97.HRMS-ESI:calcd[C26H12B2Br4F4N6+H]+821.7979；found 821.7997.
B-10：1H NMR(500MHz,CDCl3)δ9.17(d,J＝1.5Hz,1H),9.16(d,J＝1.4Hz,1H),7.87(dd,J＝8.0,1.4Hz,2H),7.79(ddd,J＝8.1,7.0,1.3Hz,2H),7.54(s,2H),7.39(s,2H),7.35(ddd,J＝7.0,5.6,1.4Hz,2H).13C NMR(125MHz,CDCl3)δ158.67,158.61,154.19,154.14,142.34,140.28,140.25,140.23,140.20,138.34,138.28,136.13,136.10,127.90,127.86,126.71,126.68,126.64,126.28,124.02,123.98,120.88,119.97.HRMS-ESI:calcd[C26H12B2Br4F2N6O+H]+799.7960；found799.7921.
实施例17
Figure BDA0004010424710000231
按照实施例1的制备方法进行制备，不同的是，将步骤(1)中的VI-1替换成等当量的VI-7，将步骤(2)中的2-氨基吡啶III-1替换成等当量的2-吡啶乙腈IV-1，制得到最终产物C-7(15mg，18％)、D-7(27mg，33％)。
C-7：1H NMR(500MHz,CDCl3)δ9.10(dd,J＝7.2,1.4Hz,2H),8.28(td,J＝7.7,1.1Hz,2H),7.79(td,J＝7.5,1.4Hz,2H),7.51(dd,J＝8.0,1.6Hz,2H),7.25(t,J＝1.1Hz,2H),7.16(t,J＝1.1Hz,2H),2.67(qd,J＝7.5,1.0Hz,8H),1.15(t,J＝7.5Hz,12H).13C NMR(125MHz,CDCl3)δ171.74,148.03,142.47,141.24,140.18,134.92,134.39,132.28,130.69,127.36,126.65,123.45,121.94,111.95,91.63,26.59,26.55,26.51,15.38,15.34,15.29.HRMS-ESI:calcd[C38H32B2F4N6+H]+671.2811；found 671.2817.
D-7：1H NMR(500MHz,CDCl3)δ9.28–9.23(m,2H),8.28(td,J＝7.8,1.2Hz,2H),7.37–7.29(m,4H),7.16(dt,J＝6.5,1.0Hz,4H),2.67(qd,J＝7.5,1.0Hz,8H),1.15(t,J＝7.5Hz,12H).13C NMR(125MHz,CDCl3)δ152.26,152.20,149.35,149.30,142.40,141.24,139.97,138.57,138.54,138.51,138.48,137.73,137.67,132.93,132.90,131.66,131.63,128.12,128.09,126.63,126.60,123.41,121.37,111.95,90.90,90.87,26.59,26.55,26.51,15.38,15.34,15.29.HRMS-ESI:calcd[C38H32B2F2N6O+H]+649.2792；found 649.2807.
实施例18
Figure BDA0004010424710000241
按照实施例1的制备方法进行制备，不同的是，将步骤(1)中的VI-1替换成等当量的VI-8，将步骤(2)中的2-氨基吡啶III-1替换成等当量的2-吡啶乙腈IV-1，制得到最终产物C-8(40mg，36％)、D-8(49mg，45％)。
C-8：1H NMR(500MHz,CDCl3)δ9.10(dd,J＝7.2,1.4Hz,2H),8.28(td,J＝7.7,1.1Hz,2H),8.00(s,2H),7.84–7.75(m,4H),7.51(dd,J＝7.8,1.5Hz,2H),7.47(dd,J＝5.0,1.7Hz,4H),7.41(td,J＝5.9,1.6Hz,4H),7.13(dd,J＝6.1,5.0Hz,4H).13C NMR(125MHz,CDCl3)δ148.02,142.47,142.40,141.55,141.47,141.45,135.01,134.39,133.03,132.16,131.69,130.69,127.96,127.94,127.36,127.04,127.00,126.96,126.73,126.67,126.62,126.56,123.40,121.35,111.95,91.88.HRMS-ESI:calcd[C46H24B2F4N6S4+H]+887.1068；found 887.1098.
D-8：1H NMR(500MHz,CDCl3)δ9.28–9.23(m,2H),8.28(td,J＝7.8,1.2Hz,2H),8.08(s,2H),7.89(s,2H),7.47(dd,J＝5.0,1.8Hz,4H),7.41(td,J＝5.9,1.6Hz,4H),7.37–7.29(m,4H),7.13(dd,J＝6.1,5.0Hz,4H).13C NMR(125MHz,CDCl3)δ152.34,152.29,149.35,149.30,142.40,141.55,141.47,141.45,138.52,138.49,138.46,138.43,137.73,137.67,133.03,132.46,132.43,131.66,131.63,131.46,128.12,128.09,127.96,127.94,127.16,127.13,127.04,127.00,126.96,126.73,126.67,126.62,123.43,121.40,111.95,91.06,91.03.HRMS-ESI:calcd[C46H24B2F2N6OS4+H]+865.1049；found 865.1007.
实施例19
Figure BDA0004010424710000251
按照实施例1的制备方法进行制备，不同的是，将步骤(1)中的VI-1替换成等当量的VI-9，将步骤(2)中的2-氨基吡啶III-1替换成等当量的2-吡啶乙腈IV-4，制得到最终产物C-9(17mg，15％)、D-9(46mg，41％)。
C-9：1H NMR(500MHz,CDCl3)δ9.18(d,J＝10.6Hz,2H),7.92–7.83(m,4H),7.33(d,J＝13.6Hz,4H),1.39(s,36H).13C NMR(125MHz,CDCl3)δ170.44,153.29,152.02,149.84,141.03,134.93,133.65,131.73,126.84,126.52,124.93,123.89,122.88,120.13,111.95,91.67,36.92,36.89,30.39,30.37.HRMS-ESI:calcd[C48H46B2F10N6+H]+919.3810；found919.3822.
D-9：1H NMR(500MHz,CDCl3)δ9.22(d,J＝10.7Hz,2H),7.79(d,J＝2.1Hz,2H),7.74(dd,J＝10.7,2.1Hz,2H),7.42(s,2H),7.33(s,2H),1.39(s,36H).13C NMR(125MHz,CDCl3)δ153.29,152.39,152.33,151.81,137.01,136.99,132.31,132.27,127.54,127.51,127.16,127.13,127.10,125.51,125.48,125.45,122.91,122.82,119.79,111.96,95.02,94.98,36.92,36.89,30.39,30.37.HRMS-ESI:calcd[C48H46B2F8N6O+H]+897.3792；found 897.3777.
实施例20
Figure BDA0004010424710000261
按照实施例1的制备方法进行制备，不同的是，将步骤(1)中的VI-1替换成等当量的VI-10，将步骤(2)中的2-氨基吡啶III-1替换成等当量的5-烯基-2-吡啶乙腈IV-5，制得到最终产物C-10(18mg，18％)、D-10(24mg，25％)。
C-10：1HNMR(500MHz,CDCl3)δ9.18(d,J＝1.6Hz,2H),8.75(s,2H),8.52(s,2H),8.17(dd,J＝6.2,1.8Hz,2H),7.43(d,J＝6.4Hz,2H),7.23–7.14(m,2H),5.80–5.73(m,2H),5.64(dd,J＝16.8,2.6Hz,1H),5.56(dd,J＝11.4,2.7Hz,1H).13C NMR(125MHz,CDCl3)δ142.90,142.60,140.92,140.17,137.49,136.98,136.86,135.79,134.54,134.22,128.33,126.49,121.94,118.68,113.91,111.95,97.99.HRMS-ESI:calcd[C34H16B2F4N10O9+H]+791.1275；found 791.1277.
D-10：1HNMR(500MHz,CDCl3)δ9.16(d,J＝1.6Hz,2H),8.74(s,2H),8.52(s,2H),8.17(dd,J＝6.2,1.8Hz,2H),7.32(d,J＝6.4Hz,2H),7.24–7.14(m,2H),5.81–5.76(m,2H),5.74(d,J＝2.6Hz,1H),5.64(dd,J＝16.8,2.6Hz,1H),5.56(dd,J＝11.4,2.7Hz,1H).13CNMR(125MHz,CDCl3)δ152.95,152.90,143.96,143.91,140.92,140.17,140.10,140.04,139.52,139.49,139.47,139.43,137.80,137.77,137.29,135.14,135.11,134.25,128.97,128.94,126.95,126.92,122.17,118.74,113.91,111.95,90.73,90.70.HRMS-ESI:calcd[C34H16B2F2N10O9+H]+769.1256；found 769.1279.
测试例1
对实施例中制得部分β-异靛蓝骨架近红外氟硼染料B-1～B-4、D-2和D-3在二氯甲烷中的光物理性质进行测试，测试结果如表1所示：
表1部分β-异靛蓝骨架近红外氟硼染料光物理性质测试数据
Figure BDA0004010424710000271
表1中：λabs为最大吸收波长；εmax为摩尔吸光系数；λem为最大发射波长；ΦF为荧光量子产率。
经过测试标明，目标产物β-异靛蓝类氟硼染料均表现在溶液中均表现出较好的光物理性质，其最大吸收峰(图2)分别是：588、601、646、660、709和800nm。β-异靛蓝类氟硼染料具有红色荧光发射(图3)和优异的光稳定性(图4)。
通过上述实施例可知，本发明提供了一类β-异靛蓝骨架近红外氟硼染料及其制备方法，该方法可以很容易地通过商业化的邻苯二甲腈的三步反应来实现，具有产物收率高、底物适用性强和后处理简单等优点。此外，所制备的β-异靛蓝染料具有高摩尔吸光系数和较高的近红外发光强度，使得其在生物成像与光诊疗等领域有着潜在的应用。
以上详细描述了本发明的优选实施方案，但是，本发明并不局限于上述实施案例中的具体细节和具体技术特征，在不与本发明思想矛盾的情况下，可以对本发明的技术方案进行简单变型和任意组合，其同样应当视为本发明所公开的内容。

Claims (10)

1.一类基于β-异靛蓝骨架的近红外氟硼染料，其特征在于，所述近红外氟硼染料的结构如下式之一：
Figure FDA0004010424700000011
其中，R1和R2各自独立地选自H、C1-C20的烷基、C3-C6的环烷基、芳香基团、卤素、烯丙基、三甲基硅烷、三氟甲基、硝基、-S-R3、-O-R3，其中R3选自H、C1-C20的烷基、C3-C6的环烷基、芳香基团；
Figure FDA0004010424700000012
表示含氮杂环，所述含氮杂环选自五元氮杂环、六元氮杂环或者苯并氮杂环中的一种。
2.根据权利要求1所述一类基于β-异靛蓝骨架的近红外氟硼染料，其特征在于，卤素为F，Cl，Br或I中的一种；芳香基团为苯环、噻吩环、呋喃环或咪唑环中的一种；
Figure FDA0004010424700000013
为咪唑、噻唑、噁唑、吡啶、嘧啶、喹啉或异喹啉中的一种。
3.权利要求1或2所述一类基于β-异靛蓝骨架近红外氟硼染料的制备方法，其特征在于，所述制备方法包括如下步骤：
步骤(1)、氩气环境下加热金属钠和第一溶剂，待金属钠全部溶解后加入邻苯二甲腈VI中进行反应，产物纯化后得到中间体二亚氨基β-异靛蓝V；
Figure FDA0004010424700000014
步骤(2)、将步骤(1)所得中间体二亚氨基β-异靛蓝V与2-氨基氮杂环III或2-氮杂环乙腈IV加入第二溶剂中反应，产物纯化后分别得到中间体I或II；
Figure FDA0004010424700000021
步骤(3)、将步骤(2)所得中间体I或II溶解于第三溶剂，加入碱和三氟化硼乙醚进行反应，产物纯化后得到最终产物A～D；
Figure FDA0004010424700000022
4.根据权利要求3所述的制备方法，其特征在于，步骤(1)中，邻苯二甲腈VI和金属钠的摩尔比为1:(1.05～1.20)。
5.根据权利要求3所述的制备方法，其特征在于，步骤(2)中，β-异靛蓝V与2-氨基氮杂环III或2-氮杂环乙腈IV的摩尔比为1：(4～5)。
6.根据权利要求3所述的制备方法，其特征在于，步骤(3)中，中间体I或II、碱和三氟化硼乙醚的摩尔比为1：(1～10)：(2～20)。
7.根据权利要求3所述的制备方法，其特征在于，第一溶剂为1-十二烷硫醇，第二溶剂和第三溶剂各自独立地选自二氯甲烷、氯仿、甲苯、乙腈、四氢呋喃、二甲基亚砜、N,N-二甲基甲酰胺、乙酸乙酯、氯苯、邻二氯苯、间二氯苯、对二氯苯、1,4-二氧六环中的一种或两种以上混合。
8.根据权利要求3所述的制备方法，其特征在于，所述碱包括有机碱和无机碱，其中有机碱为三乙胺、N,N-二异丙基乙胺、1,8-二氮杂双环[5.4.0]十一碳-7-烯、吡啶、1,5-二氮杂双环[4.3.0]壬-5-烯和三乙烯二胺中的一种或几种混合；无机碱为碳酸钠、碳酸氢钠、碳酸钾、碳酸氢钾、氢氧化钠和氢氧化钾中的一种或几种混合。
9.根据权利要求3所述的制备方法，其特征在于，步骤(1)的反应温度为100～200℃，反应时间为2～10h；步骤(2)的反应温度为150～200℃，反应时间为5～24h；步骤(3)的反应温度110～150℃，反应时间为1～5h。
10.权利要求1或2所述一类基于β-异靛蓝骨架近红外氟硼染料在生物成像与光诊疗领域的应用。
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