CN115353514A - 氟代吡啶并嘧啶酮类化合物及其合成方法 - Google Patents

氟代吡啶并嘧啶酮类化合物及其合成方法 Download PDF

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CN115353514A
CN115353514A CN202211053428.3A CN202211053428A CN115353514A CN 115353514 A CN115353514 A CN 115353514A CN 202211053428 A CN202211053428 A CN 202211053428A CN 115353514 A CN115353514 A CN 115353514A
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张新迎
沈檬洋
李皓
范学森
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Henan Normal University
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Abstract

本发明公开了氟代吡啶并嘧啶酮类化合物及其合成方法，属于有机合成技术领域。以1‑芳基取代吡唑烷酮类化合物1和偕二氟环丙烯类化合物2为原料，在铑催化剂和醋酸盐添加剂存在下，有机溶剂中升温反应，得到氟代吡啶并嘧啶酮类化合物3。本发明通过偕二氟环丙烯类化合物和1‑芳基取代吡唑烷酮之间发生的一锅串联反应，同时完成了氟代吡啶和嘧啶酮两个杂环的构建，在温和、简便的条件下高效合成了氟代吡啶并嘧啶酮类化合物。该合成方法具有底物范围广、反应条件温和、官能团耐受性好等优点。

Description

氟代吡啶并嘧啶酮类化合物及其合成方法
技术领域
本发明属于有机合成技术领域，具体涉及氟代吡啶并嘧啶酮类化合物及其合成方法。
背景技术
众所周知，含氮杂环类化合物在天然产物、药物、农用化学品和香料分子中广泛存在。此外，它们还是合成化学中常用的中间体，具有重要的研究价值。
作为一类重要的含氮稠杂环，吡啶并嘧啶酮类化合物表现出显著抗球虫、抗抑郁、平喘、抑制醛糖还原酶、抑制乙酰胆碱酯酶、抗精神病和抗过敏等药物活性，是新药开发的优势结构之一。氟原子具有独特的电子性能和空间尺寸，可显著影响有机分子的吸收和代谢过程，进而有效改善其生物活性。目前超过30％上市药物分子都含有至少一个氟原子。含有上述两种优势结构单元的氟代吡啶并嘧啶酮类化合物可能会基于加合效应而表现出显著的生物活性及理化性能，具有潜在的应用开发价值。
因此，研究并开发从简单易得的原料出发，通过简便的途径和过程合成氟代吡啶并嘧啶酮类化合物，具有十分重要的理论意义和应用前景。
发明内容
本发明解决的技术问题是提供了一类氟代吡啶并嘧啶酮类化合物及其合成方法，通过偕二氟环丙烯类化合物和1-芳基取代吡唑烷酮之间发生的一锅串联反应，同时完成了氟代吡啶和嘧啶酮两个杂环的构建，在温和、简便的条件下高效合成了氟代吡啶并嘧啶酮类化合物，该合成方法具有底物范围广、反应条件温和、官能团耐受性好等优点。
本发明所提供的氟代吡啶并嘧啶酮类化合物，其结构通式为：
Figure BDA0003824153500000011
其中，R1为C1-4烷基、C1-4烷氧基、苄氧基、卤素、氰基或三氟甲基，R2为苯基、取代苯基、萘基或噻吩基，取代苯基苯环上的取代基为一元或多元取代C1-4烷基、C1-4烷氧基、苯基、卤素、氰基、三氟甲基、C1-4烷氧羰基或硝基。
本发明还提供了上述氟代吡啶并嘧啶酮类化合物的合成方法，采用的技术方案为：
氟代吡啶并嘧啶酮类化合物的合成方法，包括如下操作：以1-芳基取代吡唑烷酮类化合物1和偕二氟环丙烯类化合物2为原料，在铑催化剂和醋酸盐添加剂存在下，有机溶剂中升温反应，得到氟代吡啶并嘧啶酮类化合物3。
反应方程式为：
Figure BDA0003824153500000021
其中，R1为C1-4烷基、C1-4烷氧基、苄氧基、卤素、氰基或三氟甲基，R2为苯基、取代苯基、萘基或噻吩基，取代苯基苯环上的取代基为一元或多元取代的C1-4烷基、C1-4烷氧基、苯基、卤素、氰基、三氟甲基、C1-4烷氧羰基或硝基。
进一步地，在上述技术方案中，所述铑催化剂为二氯(五甲基环戊二烯基)合铑(III)二聚体([RhCp*Cl2]2)或二(六氟锑酸)三乙腈(五甲基环戊二烯基)铑(III) ([RhCp*(MeCN)3](SbF6)2)。
进一步地，在上述技术方案中，所述醋酸盐添加剂为醋酸钠、醋酸钾或醋酸铯。
进一步地，在上述技术方案中，所述有机溶剂为起到溶解原料的作用，优选二氯乙烷、二氯甲烷、乙腈、四氢呋喃、乙酸乙酯、甲苯或1,4-二氧六环。
进一步地，在上述技术方案中，所述1-芳基取代吡唑烷酮类化合物1、偕二氟环丙烯类化合物2、铑催化剂与醋酸盐添加剂摩尔比为1.5-2:1-1.2:0.025 -0.05:1-2。
进一步地，在上述技术方案中，所述反应温度为60-80℃。
进一步地，在上述技术方案中，所述反应在空气氛围下进行。
发明有益效果：
本发明与现有技术相比具有以下优点：(1)通过1-芳基取代吡唑烷酮和偕二氟环丙烯类化合物之间的一锅串联反应，同时完成了氟代吡啶和嘧啶酮两个杂环的构建，整个过程原子经济性高，反应条件温和，过程简单而高效；(2)该反应还具有原料廉价易得、底物适用范围广、官能团耐受性好等优点。
附图说明
图1为实施例1中化合物3a的X-射线单晶衍射图。
具体实施方式
以下通过实施例对本发明的上述内容做进一步详细说明，但不应该将此理解为本发明上述主题的范围仅限于以下的实施例，凡基于本发明上述内容实现的技术均属于本发明的范围。
实施例1
Figure BDA0003824153500000031
向15mL反应管中依次加入化合物1a、铑催化剂、添加剂和有机溶剂，然后加入化合物2a，在空气条件下将反应管密封，将其置于加热模块中升温搅拌反应。待反应结束后，将体系冷却至室温，用硅藻土过滤，滤液浓缩，过硅胶柱分离(石油醚/乙酸乙酯＝3/1)得到白色固体产物3a。
通过改变反应的铑催化剂、添加剂、反应温度和物料比等反应条件，得到一系列的结果，见表1。
表1不同条件下3a的合成a
Figure BDA0003824153500000032
Figure BDA0003824153500000041
实施例2
Figure BDA0003824153500000042
向15mL耐压管中依次加入1a(76.1mg,0.4mmol)、二氯(五甲基环戊二烯基)合铑(III)二聚体(6.2mg,0.01mmol)、醋酸钾(19.6mg,0.2mmol)和二氯甲烷(2mL)，随后加入2a(30.4mg,0.2mmol)，然后将反应管密封，将其置于 80℃油浴中反应18h。反应结束后，将反应体系冷却至室温，用硅藻土过滤，滤液浓缩，过硅胶柱分离(石油醚/乙酸乙酯＝3/1)得到白色固体产物3a(50.3mg, 78％)。该化合物的表征数据为：1H NMR(400MHz,CDCl3):δ7.42-7.40(m,2H), 7.37-7.33(m,3H),7.14(t,J＝7.6Hz,1H),7.03(d,J＝7.2Hz,1H),6.83(s,1H), 6.77-6.72(m,2H),6.27(d,J＝12.4Hz,1H),3.66(dd,J＝14.4Hz,1.6Hz,1H),2.96(d,J＝14.4Hz,1H),1.27(s,3H),1.19(s,3H).13C{1H}NMR(100MHz,CDCl3):δ 176.2,152.9(d,JC-F＝259.1Hz),141.5(d,JC-F＝2.3Hz),139.4,129.13(d,JC-F＝3.0 Hz),129.08,128.7,127.9(d,JC-F＝5.3Hz),125.8,118.4,116.9(d,JC-F＝6.7Hz), 109.9,104.3(d,JC-F＝16.4Hz),75.6(d,JC-F＝26.6Hz),48.8(d,JC-F＝2.1Hz),40.8, 26.0,22.6.19F NMR(376MHz,CDCl3):δ-128.4(d,J＝12.4Hz).HRMS(ESI)m/z: [M+H]+Calcd for C20H20FN2O323.1554；Found 323.1549.
实施例3
依照实施例2的方法和步骤a,b，通过改变反应物1和反应物2，可以合成出各种氟代吡啶并嘧啶酮类化合物3，具体结果如下：
Figure BDA0003824153500000051
a反应条件：1(0.4mmol),2(0.2mmol),[Cp*RhCl2]2(0.01mmol),KOAc(0.2mmol),二氯甲烷(2mL),80℃,18h,空气氛围；b分离收率。
代表性产物表征数据如下： 5-Fluoro-2,2,8-trimethyl-4a-phenyl-4,4a-dihydro-1H-pyrimido[1,2-a]quinolin-3( 2H)-one(3b)
1H NMR(400MHz,CDCl3):δ7.41-7.39(m,2H),7.35-7.32(m,3H),6.94(d,J＝8.4Hz,1H),6.85(s,2H),6.62(d,J＝8.4Hz,1H),6.22(d,J＝12.0Hz,1H),3.61(dd,J ＝14.0Hz,2.0Hz,1H),2.94(d,J＝14.4Hz,1H),2.25(s,3H),1.27(s,3H),1.18(s, 3H).13C{1H}NMR(100MHz,CDCl3):δ176.2,153.2(d,JC-F＝258.9Hz),141.5(d, JC-F＝1.8Hz),137.3,129.6(d,JC-F＝1.9Hz),129.0,128.7,128.4(d,JC-F＝5.3Hz) 127.6,125.8,116.9(d,JC-F＝6.8Hz),110.0,104.2(d,JC-F＝15.8Hz),75.6(d,JC-F＝ 26.1Hz),49.0(d,JC-F＝1.4Hz),40.8,26.1,22.6,20.2.19F NMR(376MHz,CDCl3): δ-128.2(d,J＝12.8Hz).HRMS(ESI)m/z:[M+H]+Calcd for C21H22FN2O 337.1711； Found 337.1704.
8-Ethyl-5-fluoro-2,2-dimethyl-4a-phenyl-4,4a-dihydro-1H-pyrimido[1,2-a]quinol in-3(2H)-one(3c)
1H NMR(400MHz,CDCl3):δ7.42-7.40(m,2H),7.37-7.33(m,3H),6.97(dd,J＝8.4Hz,2.0Hz,1H),6.87(d,J＝1.6Hz,1H),6.75(s,1H),6.65(d,J＝8.4Hz,1H), 6.24(d,J＝12.4Hz,1H),3.62(dd,J＝14.4Hz,2.0Hz,1H),2.94(d,J＝14.4Hz, 1H),2.56(q,J＝7.6Hz,2H),1.28(s,3H),1.22(t,J＝7.6Hz,3H),1.18(s,3H). 13C{1H}NMR(100MHz,CDCl3):δ176.1,153.1(d,JC-F＝259.3Hz),141.6(d,JC-F＝1.7Hz),137.5,134.1,129.0,128.7,128.4(d,JC-F＝2.1Hz),127.2(d,JC-F＝5.9Hz), 125.8,116.9(d,JC-F＝8.0Hz),109.9,104.4(d,JC-F＝15.9Hz),75.6(d,JC-F＝26.5 Hz),48.9(d,JC-F＝2.1Hz),40.8,27.6,26.1,22.6,15.6.19F NMR(376MHz,CDCl3): δ-128.6(d,J＝9.8Hz).HRMS(ESI)m/z:[M+H]+Calcdfor C22H24FN2O 351.1867； Found 351.1845.
5-Fluoro-8-isopropyl-2,2-dimethyl-4a-phenyl-1,2,4,4a-tetrahydro-3H-pyrimido[1, 2-a]quinolin-3-one(3d)
1H NMR(600MHz,CDCl3):δ7.42-7.40(m,2H),7.37-7.33(m,3H),6.99(dd,J＝8.4Hz,1.8Hz,1H),6.89(d,J＝2.4Hz,1H),6.65(d,J＝8.4Hz,1H),6.62(s,1H), 6.26(d,J＝12.6Hz,1H),3.63(dd,J＝13.8Hz,1.8Hz,1H),2.94(d,J＝13.8Hz, 1H),2.84-2.80(m,1H),1.28(s,3H),1.23(d,J＝6.6Hz,6H),1.18(s,3H).13C{1H} NMR(150MHz,CDCl3):δ176.1,152.9(d,JC-F＝258.8Hz),141.6,138.8,137.5, 129.0,128.7,127.0(d,JC-F＝2.1Hz),125.9(d,JC-F＝4.8Hz),125.8,116.7(d,JC-F＝ 5.3Hz),109.8,104.5(d,JC-F＝15.6Hz),75.7(d,JC-F＝27.3Hz),48.9,40.8,32.9, 26.2,24.1,24.0,22.7.19F NMR(565MHz,CDCl3):δ-128.9(d,J＝12.4Hz).HRMS (ESI)m/z:[M+Na]+CalcdforC23H25FN2NaO387.1843；Found387.1838.
8-(Benzyloxy)-5-fluoro-2,2-dimethyl-4a-phenyl-1,2,4,4a-tetrahydro-3H-pyrimido [1,2-a]quinolin-3-one(3e)
1H NMR(400MHz,CDCl3):δ7.44-7.31(m,10H),6.78(dd,J＝9.2Hz,2.8Hz,1H),6.72-6.69(m,2H),6.62(d,J＝9.2Hz,1H),6.23(d,J＝12.0Hz,1H),5.01(s,2H), 3.54(dd,J＝13.6Hz,1.6Hz,1H),2.93(d,J＝14.4Hz,1H),1.28(s,3H),1.20(s, 3H).13C{1H}NMR(100MHz,CDCl3):δ176.1,154.1(d,JC-F＝261.6Hz),151.7, 141.0(d,JC-F＝1.9Hz),137.3,134.0,129.1,128.7,128.6,128.0,127.5,125.8,118.4 (d,JC-F＝7.2Hz),115.3(d,JC-F＝2.7Hz),114.4(d,JC-F＝6.2Hz),111.3,104.4(d, JC-F＝16.8Hz),75.6(d,JC-F＝25.7Hz),70.8,49.5,40.6,26.2,22.7.19FNMR(376 MHz,CDCl3):δ-126.5(d,J＝12.4Hz).HRMS(ESI)m/z:[M+H]+CalcdforC27H26 FN2O2429.1973；Found429.1979.
5,8-Difluoro-2,2-dimethyl-4a-phenyl-4,4a-dihydro-1H-pyrimido[1,2-a]quinolin-3 (2H)-one(3f)
1H NMR(400MHz,CDCl3):δ7.40-7.34(m,5H),6.84(td,J＝8.4Hz,2.8Hz,1H), 6.78(dd,J＝8.4Hz,2.8Hz,1H),6.74(s,1H),6.63(dd,J＝9.2Hz,4.4Hz,1H),6.24 (d,J＝12.0Hz,1H),3.56(dd,J＝14.4Hz,2.4Hz,1H),2.97(d,J＝14.4Hz,1H), 1.28(s,3H),1.20(s,3H).13C{1H}NMR(100MHz,CDCl3):δ175.9,155.9(d,JC-F＝ 235.4Hz),154.3(d,JC-F＝261.9Hz),140.9(d,JC-F＝2.1Hz),135.8(d,JC-F＝1.8Hz), 129.2,128.8,125.9,118.5(t,JC-F＝8.0Hz),115.1(dd,JC-F＝22.2Hz,2.9Hz),114.1 (dd,JC-F＝24.1Hz,6.9Hz),111.1(d,JC-F＝7.2Hz),103.8(dd,JC-F＝17.6Hz,2.3 Hz),75.5(d,JC-F＝27.2Hz),49.5(d,JC-F＝1.3Hz),40.7,26.0,22.6.19FNMR(376 MHz,CDCl3):δ-125.6(d,J＝10.9Hz),-127.0(td,J＝8.6Hz,3.8Hz).HRMS(ESI) m/z:[M+H]+CalcdforC20H19F2N2O341.1460；Found341.1456.
8-Chloro-5-fluoro-2,2-dimethyl-4a-phenyl-4,4a-dihydro-1H-pyrimido[1,2-a]quin olin-3(2H)-one(3g)
1H NMR(600MHz,CDCl3):δ7.40-7.35(m,5H),7.08(dd,J＝9.0Hz,2.4Hz,1H), 7.02(d,J＝2.4Hz,1H),6.82(s,1H),6.65(d,J＝8.4Hz,1H),6.22(d,J＝12.0Hz, 1H),3.58(dd,J＝14.4Hz,1.8Hz,1H),2.98(d,J＝14.4Hz,1H),1.26(s,3H),1.19 (s,3H).13C{1H}NMR(100MHz,CDCl3):δ175.9,153.8(d,JC-F＝262.4Hz),141.1 (d,JC-F＝2.4Hz),138.1,129.3,128.8,128.6(d,JC-F＝2.5Hz),127.2(d,JC-F＝5.8 Hz),125.7,123.0,118.6(d,JC-F＝8.5Hz),111.2,103.5(d,JC-F＝16.2Hz),75.4(d, JC-F＝26.3Hz),49.2(d,JC-F＝2.3Hz),40.8,25.9,22.5.19F NMR(565MHz,CDCl3): δ-125.9(d,J＝13.0Hz).HRMS(ESI)m/z:[M+Na]+CalcdforC20H18ClFN2NaO 379.0984；Found379.0968.
8-Bromo-5-fluoro-2,2-dimethyl-4a-phenyl-1,2,4,4a-tetrahydro-3H-pyrimido[1,2- a]quinolin-3-one(3h)
1H NMR(600MHz,CDCl3):δ7.39-7.35(m,5H),7.21(dd,J＝8.4Hz,1.8Hz,1H), 7.15(d,J＝2.4Hz,1H),6.82(s,1H),6.60(d,J＝9.0Hz,1H),6.22(d,J＝12.0Hz, 1H),3.58(dd,J＝13.8Hz,1.8Hz,1H),2.97(d,J＝14.4Hz,1H),1.26(s,3H),1.19 (s,3H).13C{1H}NMR(100MHz,CDCl3):δ175.8,153.6(d,JC-F＝261.8Hz),141.1 (d,JC-F＝2.1Hz),138.5,131.5(d,JC-F＝1.8Hz),130.0(d,JC-F＝6.1Hz),129.3, 128.8,125.7,119.0(d,JC-F＝8.1Hz),111.6,110.0,103.4(d,JC-F＝18.0Hz),75.4(d, JC-F＝27.1Hz),49.1,40.8,25.9,22.5.19FNMR(565MHz,CDCl3):δ-125.9(d,J＝ 10.2Hz).HRMS(ESI)m/z:[M+Na]+CalcdforC20H18BrFN2NaO423.0479；Found 423.0467.
5-Fluoro-2,2-dimethyl-3-oxo-4a-phenyl-2,3,4,4a-tetrahydro-1H-pyrimido[1,2-a]q uinoline-8-carbonitrile(3i)
1H NMR(600MHz,CDCl3):δ7.43-7.38(m,6H),7.31(d,J＝1.2Hz,1H),6.78(d,J ＝8.4Hz,1H),6.70(s,1H),6.29(d,J＝12.0Hz,1H),3.68(dd,J＝14.4Hz,1.2Hz, 1H),3.04(d,J＝14.4Hz,1H),1.26(s,3H),1.21(s,3H).13C{1H}NMR(100MHz, CDCl3):δ175.3,153.4(d,JC-F＝261.2Hz),142.4,140.9(d,JC-F＝2.0Hz),133.4(d, JC-F＝2.2Hz),131.3(d,JC-F＝6.5Hz),129.7,129.0,125.6,119.2,117.4(d,JC-F＝8.1 Hz),110.1,103.1(d,JC-F＝17.4Hz),101.0,75.4(d,JC-F＝27.0Hz),49.1(d,JC-F＝ 1.3Hz),41.1,25.7,22.5.19FNMR(376MHz,CDCl3):δ-125.4(d,J＝13.9Hz). HRMS(ESI)m/z:[M+Na]+Calcd forC21H18FN3NaO2370.1326；Found370.1302.
5-Fluoro-2,2-dimethyl-4a-phenyl-8-(trifluoromethyl)-1,2,4,4a-tetrahydro-3H-pyr imido[1,2-a]quinolin-3-one(3j)
1H NMR(400MHz,CDCl3):δ7.41-7.37(m,6H),7.28(d,J＝2.0Hz,1H),6.79(d,J ＝8.8Hz,2H),6.31(d,J＝12.0Hz,1H),3.69(dd,J＝12.4Hz,2.0Hz,1H),3.03(d,J ＝14.4Hz,1H),1.27(s,3H),1.21(s,3H).13C{1H}NMR(150MHz,CDCl3):δ175.6, 153.4(d,JC-F＝260.6Hz),141.8,141.2(d,JC-F＝2.3Hz),129.4,128.9,125.7,125.6 (q,JC-F＝211.4Hz),125.3,123.5,120.4(q,JC-F＝32.1Hz),116.8(d,JC-F＝9.6Hz), 109.5,103.6(d,JC-F＝16.7Hz),75.5(d,JC-F＝28.1Hz),49.1,41.0,25.8,22.5.19F NMR(376MHz,CDCl3):δ-61.5(s),-126.2(d,J＝9.8Hz).HRMS(ESI)m/z: [M+Na]+CalcdforC21H18F4N2NaO2413.1247；Found413.1229.
5-Fluoro-2,2,9-trimethyl-4a-phenyl-1,2,4,4a-tetrahydro-3H-pyrimido[1,2-a]quino lin-3-one(3k)
1H NMR(600MHz,CDCl3):δ7.41-7.39(m,2H),7.36-7.33(m,3H),6.92(d,J＝7.2Hz,1H),6.75(s,1H),6.58(d,J＝7.8Hz,1H),6.54(s,1H),6.24(d,J＝12.0Hz,1H), 3.65(dd,J＝13.8Hz,1.2Hz,1H),2.94(d,J＝13.8Hz,1H),2.29(s,3H),1.28(s, 3H),1.20(s,3H).13C{1H}NMR(150MHz,CDCl3):δ176.1,152.4(d,JC-F＝243.2 Hz),141.6,139.4,139.1(d,JC-F＝2.4Hz),129.0,128.7,127.7(d,JC-F＝5.0Hz), 125.7,119.3,114.4(d,JC-F＝8.0Hz),110.7,104.2(d,JC-F＝15.9Hz),75.6(d,JC-F＝ 26.4Hz),48.8,40.8,26.0,22.6,22.0.19FNMR(376MHz,CDCl3):δ-130.1(d,J＝ 13.2Hz).HRMS(ESI)m/z:[M+Na]+Calcd forC21H21FN2NaO359.1530；Found 359.1525.
5-Fluoro-9-methoxy-2,2-dimethyl-4a-phenyl-1,2,4,4a-tetrahydro-3H-pyrimido[1, 2-a]quinolin-3-one(3l)
1H NMR(600MHz,CDCl3):δ7.40-7.39(m,2H),7.37-7.33(m,3H),6.95(d,J＝8.4Hz,1H),6.70(s,1H),6.31(d,J＝8.4Hz,1H),6.30(s,1H),6.22(d,J＝12.6Hz,1H), 3.79(s,3H),3.57(d,J＝13.8Hz,1H),2.76(d,J＝14,4Hz,1H),1.28(s,3H),1.18(s, 3H).13C{1H}NMR(100MHz,CDCl3):δ175.9,160.9(d,JC-F＝2.3Hz),151.6(d, JC-F＝255.8Hz),141.7(d,JC-F＝2.3Hz),140.8,129.0,128.7,128.6,125.7,110.4(d, JC-F＝7.3Hz),103.8(d,JC-F＝16.8Hz),102.4,97.6,75.4(d,JC-F＝26.6Hz),55.3, 49.0(d,JC-F＝1.8Hz),40.8,26.0,22.6.19F NMR(376MHz,CDCl3):δ-132.4(d,J＝12.8Hz).HRMS(ESI)m/z:[M+Na]+Calcd forC21H21FN2NaO2375.1479；Found 375.1473.
9-Chloro-5-fluoro-2,2-dimethyl-4a-phenyl-1,2,4,4a-tetrahydro-3H-pyrimido[1,2- a]quinolin-3-one(3m)
1H NMR(600MHz,CDCl3):δ7.40-7.35(m,5H),6.95(d,J＝8.4Hz,1H),6.92(s, 1H),6.73(dd,J＝7.8Hz,1.2Hz,1H),6.71(s,1H),6.24(d,J＝12.0Hz,1H),3.56 (dd,J＝14.4Hz,1.8Hz,1H),2.98(d,J＝13.8Hz,1H),1.28(s,3H),1.20(s,3H). 13C{1H}NMR(150MHz,CDCl3):δ175.8,153.0(d,JC-F＝260.0Hz),141.2(d,JC-F＝2.1Hz),140.4,134.6(d,JC-F＝3.9Hz),129.3,128.8,128.7(d,JC-F＝6.0Hz),125.7, 118.4,115.6(d,JC-F＝9.2Hz),110.2,103.5(d,JC-F＝18.0Hz),75.3(d,JC-F＝25.5 Hz),49.1,40.8,25.9,22.5.19FNMR(565MHz,CDCl3):δ-127.7(d,J＝12.4Hz). HRMS(ESI)m/z:[M+Na]+Calcd forC20H18ClFN2NaO379.0984；Found379.0966.
9-Bromo-5-fluoro-2,2-dimethyl-4a-phenyl-1,2,4,4a-tetrahydro-3H-pyrimido[1,2- a]quinolin-3-one(3n)
1HNMR(600MHz,CDCl3):δ7.38-7.36(m,5H),6.90-6.87(m,2H),6.85(s,1H), 6.78(s,1H),6.24(d,J＝12.0Hz,1H),3.55(d,J＝14.4Hz,1H),2.97(d,J＝14.4Hz, 1H),1.29(s,3H),1.20(s,3H).13C{1H}NMR(100MHz,CDCl3):δ175.7,153.1(d, JC-F＝260.8Hz),141.1(d,JC-F＝2.6Hz),140.5,129.3,128.9(d,JC-F＝5.9Hz),128.8, 125.6,122.7(d,JC-F＝2.6Hz),121.4,116.1(d,JC-F＝7.7Hz),113.1,103.6(d,JC-F＝ 16.3Hz),75.3(d,JC-F＝26.8Hz),49.1(d,JC-F＝2.1Hz),40.8,25.9,22.5.19F NMR (376MHz,CDCl3):δ-127.3(d,J＝10.9Hz).HRMS(ESI)m/z:[M+Na]+Calcd for C20H18BrFN2NaO423.0479；Found423.0468.
5,10-Difluoro-2,2-dimethyl-4a-phenyl-1,2,4,4a-tetrahydro-3H-pyrimido[1,2-a]qui nolin-3-one(3o)
1HNMR(600MHz,CDCl3):δ7.51(d,J＝7.8Hz,2H),7.34-7.31(m,3H),6.91-6.87 (m,1H),6.84-6.79(m,2H),6.32(s,1H),6.29(d,J＝11.4Hz,1H),3.76(d,J＝13.2 Hz,1H),3.16(d,J＝13.2Hz,1H),1.39(s,3H),1.23(s,3H).13C{1H}NMR(100 MHz,CDCl3):δ175.5,155.4(d,JC-F＝272.1Hz),152.8(d,JC-F＝240.5Hz),141.1(d, JC-F＝3.5Hz),129.2,128.8,128.3(d,JC-F＝8.1Hz),125.5,124.7(dd,JC-F＝7.0Hz, 3.1Hz),122.8(dd,JC-F＝5.5Hz,2.7Hz),122.3(d,JC-F＝8.2Hz),116.3(d,JC-F＝20.0Hz),103.2(dd,JC-F＝17.0Hz,3.9Hz),75.1(d,JC-F＝23.0Hz),55.1(d,JC-F＝ 10.1Hz),40.0,23.7,23.5.19F NMR(565MHz,CDCl3):δ-118.2(d,J＝13.6Hz), -124.5(d,J＝13.6Hz).HRMS(ESI)m/z:[M+Na]+Calcd forC20H18F2N2NaO 363.1279；Found363.1270.
5-Fluoro-2,2-dimethyl-4a-phenyl-1,2,4,4a-tetrahydro-3H-benzo[g]pyrimido[1,2-a] quinolin-3-one(3p)
1H NMR(600MHz,CDCl3):δ7.68(d,J＝8.4Hz,1H),7.58(d,J＝8.4Hz,1H),7.52 (s,1H),7.37-7.35(m,3H),7.33-7.32(m,3H),7.27-7.24(m,1H),6.94(s,1H),6.73(s, 1H),6.46(d,J＝12.0Hz,1H),3.78(d,J＝13.8Hz,1H),2.98(d,J＝14.4Hz,1H), 1.32(s,3H),1.25(s,3H).13C{1H}NMR(150MHz,CDCl3):δ176.1,155.4(d,JC-F＝ 263.4Hz),140.6(d,JC-F＝2.1Hz),138.0,134.7,129.2,128.8,127.9,127.3,126.8(d, JC-F＝7.7Hz),126.7,126.2,125.5,123.5,120.1(d,JC-F＝8.1Hz),105.2,104.5(d, JC-F＝17.4Hz),75.0(d,JC-F＝26.4Hz),49.1,40.7,26.2,22.6.19F NMR(565MHz, CDCl3):δ-126.3(d,J＝11.9Hz).HRMS(ESI)m/z:[M+Na]+Calcd for C24H21FN2NaO395.1530；Found395.1519.
5-Fluoro-2,2-dimethyl-4a-(p-tolyl)-1,2,4,4a-tetrahydro-3H-pyrimido[1,2-a]quinol in-3-one(3q)
1H NMR(600MHz,CDCl3):δ7.28(d,J＝7.8Hz,2H),7.16-7.12(m,3H),7.03(d,J ＝7.2Hz,1H),6.76-6.71(m,2H),6.66(s,1H),6.26(d,J＝12.0Hz,1H),3.64(d,J＝ 13.8Hz,1H),2.97(d,J＝13.8Hz,1H),2.33(s,3H),1.27(s,3H),1.19(s,3H). 13C{1H}NMR(150MHz,CDCl3):δ176.0,153.0(d,JC-F＝257.7Hz),139.5,139.1, 138.6,129.4,129.1(d,JC-F＝2.1Hz),127.9(d,JC-F＝7.1Hz),125.7,118.3,117.0(d, JC-F＝7.7Hz),109.9,104.1(d,JC-F＝16.1Hz),75.5(d,JC-F＝27.3Hz),48.7,40.8, 26.1,22.6,21.1.19F NMR(565MHz,CDCl3):δ-128.7(d,J＝12.4Hz).HRMS(ESI) m/z:[M+Na]+Calcd for C21H21FN2NaO359.1530；Found359.1518.
4a-(4-(tert-butyl)phenyl)-5-Fluoro-2,2-dimethyl-1,2,4,4a-tetrahydro-3H-pyrimido [1,2-a]quinolin-3-one(3r)
1H NMR(400MHz,CDCl3):δ7.36-7.29(m,4H),7.12(t,J＝7.6Hz,1H),7.02(dd,J ＝7.2Hz,1.2Hz,1H),6.76-6.71(m,2H),6.66(s,1H),6.25(d,J＝12.0Hz,1H),3.64 (dd,J＝14.0Hz,2.0Hz,1H),3.00(d,J＝14.0Hz,1H),1.29(s,9H),1.27(s,3H), 1.20(s,3H).13C{1H}NMR(100MHz,CDCl3):δ176.0,153.1(d,JC-F＝259.5Hz), 152.1,139.5,138.4(d,JC-F＝2.2Hz),129.0(d,JC-F＝1.9Hz),127.8(d,JC-F＝5.5Hz), 125.6,125.4,118.3,117.1(d,JC-F＝6.8Hz),109.9,104.1(d,JC-F＝16.3Hz),75.5(d, JC-F＝26.2Hz),48.8(d,JC-F＝1.3Hz),40.8,34.6,31.3,26.0,22.6.19F NMR(376 MHz,CDCl3):δ-128.4(d,J＝10.5Hz).HRMS(ESI)m/z:[M+Na]+Calcd for C24H27FN2NaO401.2000；Found401.1991.
4a-([1,1'-biphenyl]-4-yl)-5-Fluoro-2,2-dimethyl-1,2,4,4a-tetrahydro-3H-pyrimido [1,2-a]quinolin-3-one(3s)
1H NMR(400MHz,CDCl3):δ7.58-7.54(m,4H),7.48-7.41(m,4H),7.35(t,J＝7.2Hz,1H),7.15(t,J＝7.6Hz,1H),7.05(dd,J＝7.2Hz,1.2Hz,1H),6.80(s,1H),6.76 (t,J＝8.0Hz,2H),6.30(d,J＝12.0Hz,1H),3.69(dd,J＝14.4Hz,2.0Hz,1H),3.03 (d,J＝14.4Hz,1H),1.29(s,3H),1.22(s,3H).13C{1H}NMR(100MHz,CDCl3):δ 176.1,152.9(d,JC-F＝259.4Hz),142.0,140.4(d,JC-F＝1.3Hz),140.1,139.4,129.2 (d,JC-F＝2.3Hz),128.9,128.0(d,JC-F＝6.5Hz),127.7,127.4,127.2,126.2,118.5, 116.9(d,JC-F＝7.5Hz),110.0,104.3(d,JC-F＝15.6Hz),75.5(d,JC-F＝26.9Hz),48.9, 40.9,26.1,22.6.19FNMR(565MHz,CDCl3):δ-128.6(d,J＝11.9Hz).HRMS(ESI) m/z:[M+Na]+Calcd forC26H23FN2NaO421.1687；Found421.1671.
5-Fluoro-4a-(4-fluorophenyl)-2,2-dimethyl-1,2,4,4a-tetrahydro-3H-pyrimido[1,2- a]quinolin-3-one(3t)
1H NMR(400MHz,CDCl3):δ7.41-7.37(m,2H),7.15(t,J＝8.8Hz,1H),7.05-7.01(m,3H),6.82(s,1H),6.78-6.73(m,2H),6.28(d,J＝12.0Hz,1H),3.67(dd,J＝14.0 Hz,2.0Hz,1H),2.94(d,J＝14.4Hz,1H),1.27(s,3H),1.19(s,3H).13C{1H}NMR (100MHz,CDCl3):δ176.0,163.0(d,JC-F＝246.7Hz),152.7(d,JC-F＝259.3Hz), 139.3,137.5(d,JC-F＝3.0Hz),129.2(d,JC-F＝2.8Hz),128.0(d,JC-F＝5.8Hz),127.7 (d,JC-F＝8.5Hz),118.6,116.8(d,JC-F＝7.5Hz),115.6(d,JC-F＝21.7Hz),110.0, 104.3(d,JC-F＝16.1Hz),75.2(d,JC-F＝26.9Hz),48.8(d,JC-F＝1.4Hz),40.8,26.0, 22.6.19FNMR(376MHz,CDCl3):δ-112.7–-112.8(m),-128.7(d,J＝10.5Hz). HRMS(ESI)m/z:[M+H]+Calcd for C20H19F2N2O341.1460；Found341.1458.
4a-(4-Chlorophenyl)-5-fluoro-2,2-dimethyl-1,2,4,4a-tetrahydro-3H-pyrimido[1,2- a]quinolin-3-one(3u)
1H NMR(600MHz,CDCl3):δ7.36(d,J＝8.4Hz,2H),7.31(d,J＝8.4Hz,2H),7.15 (t,J＝7.2Hz,1H),7.11(s,1H),7.04(d,J＝7.2Hz,1H),6.78-6.74(m,2H),6.27(d, J＝12.0Hz,1H),3.68(dd,J＝13.8Hz,1.2Hz,1H),2.93(d,J＝14.4Hz,1H),1.26 (s,3H),1.19(s,3H).13C{1H}NMR(150MHz,CDCl3):δ176.1,152.6(d,JC-F＝ 259.7Hz),140.2(d,JC-F＝2.0Hz),139.3,135.1,129.3(d,JC-F＝2.6Hz),128.9, 128.0(d,JC-F＝5.6Hz),127.3,118.7,116.8(d,JC-F＝7.1Hz),110.0,104.4(d,JC-F＝ 15.5Hz),75.2(d,JC-F＝26.6Hz),48.9,40.8,26.0,22.6.19FNMR(565MHz,CDCl3): δ-128.4(d,J＝13.0Hz).HRMS(ESI)m/z:[M+Na]+Calcd for C20H18ClFN2NaO 379.0984；Found379.0965.
4a-(4-Bromophenyl)-5-fluoro-2,2-dimethyl-1,2,4,4a-tetrahydro-3H-pyrimido[1,2- a]quinolin-3-one(3v)
1H NMR(400MHz,CDCl3):δ7.48-7.45(m,2H),7.31-7.26(m,2H),7.17-7.13(m,1H),7.08(s,1H),7.03(dd,J＝7.6Hz,1.6Hz,1H),6.78-6.73(m,2H),6.27(d,J＝ 12.4Hz,1H),3.68(dd,J＝14.4Hz,2.4Hz,1H),2.93(d,J＝14.4Hz,1H),1.26(s, 3H),1.18(s,3H).13C{1H}NMR(100MHz,CDCl3):δ176.1,152.5(d,JC-F＝259.6 Hz),140.8(d,JC-F＝1.2Hz),139.3,131.9,129.3(d,JC-F＝2.1Hz),128.0(d,JC-F＝ 5.9Hz),127.6,123.4,118.7,116.8(d,JC-F＝7.9Hz),110.0,104.5(d,JC-F＝16.0Hz), 75.3(d,JC-F＝26.8Hz),48.9(d,JC-F＝1.9Hz),40.8,26.0,22.6.19FNMR(376MHz, CDCl3):δ-128.4(d,J＝12.8Hz).HRMS(ESI)m/z:[M+Na]+Calcd for C20H18BrFN2NaO423.0479；Found423.0467.
4-(5-Fluoro-2,2-dimethyl-3-oxo-1,2,3,4-tetrahydro-4aH-pyrimido[1,2-a]quinolin- 4a-yl)benzonitrile(3w)
1H NMR(600MHz,CDCl3):δ7.83(s,1H),7.63(d,J＝8.4Hz,2H),7.59(d,J＝9.0 Hz,2H),7.18(t,J＝8.4Hz,1H),7.05(dd,J＝7.8Hz,1.8Hz,1H),6.80-6.78(m,2H), 6.29(d,J＝12.0Hz,1H),3.75(dd,J＝14.4Hz,1.8Hz,1H),2.87(d,J＝15.0Hz, 1H),1.26(s,3H),1.19(s,3H).13C{1H}NMR(150MHz,CDCl3):δ176.3,152.1(d, JC-F＝260.3Hz),146.7(d,JC-F＝2.6Hz),139.2,132.6,129.5(d,JC-F＝2.6Hz),128.2 (d,JC-F＝6.2Hz),126.7,119.0,118.2,116.6(d,JC-F＝7.7Hz),113.0,110.2,104.8(d, JC-F＝14.7Hz),75.3(d,JC-F＝27.2Hz),49.2,40.8,25.8,22.6.19FNMR(565MHz, CDCl3):δ-127.9(d,J＝13.0Hz).HRMS(ESI)m/z:[M+H]+Calcd for C21H19FN3O 348.1507；Found348.1500.
5-Fluoro-2,2-dimethyl-4a-(4-(trifluoromethyl)phenyl)-1,2,4,4a-tetrahydro-3H-py rimido[1,2-a]quinolin-3-one(3x)
1H NMR(400MHz,CDCl3):δ7.72(s,1H),7.59(s,4H),7.17(t,J＝7.6Hz,1H), 7.05(d,J＝7.2Hz,1H),6.80-6.76(m,2H),6.28(d,J＝12.0Hz,1H),3.73(d,J＝ 14.4Hz,1H),2.91(d,J＝14.4Hz,1H),1.27(s,3H),1.19(s,3H).13C{1H}NMR (100MHz,CDCl3):δ176.3,152.4(d,JC-F＝261.0Hz),145.6,139.3,131.2(q,JC-F＝ 31.8Hz),129.4(d,JC-F＝2.0Hz),128.1(d,JC-F＝5.9Hz),126.3,125.7(q,JC-F＝3.7 Hz),123.8(q,JC-F＝270.7Hz),118.8,116.7(d,JC-F＝7.3Hz),110.1,104.6(d,JC-F＝ 16.1Hz),75.3(d,JC-F＝26.9Hz),49.1,40.8,25.9,22.6.19FNMR(565MHz,CDCl3): δ-62.6(s),-127.8(d,J＝11.9Hz).HRMS(ESI)m/z:[M+H]+Calcd for C21H19F4N2O 391.1428；Found391.1429.
Methyl4-(5-fluoro-2,2-dimethyl-3-oxo-1,2,3,4-tetrahydro-4aH-pyrimido[1,2-a] quinolin-4a-yl)benzoate(3y)
1H NMR(400MHz,CDCl3):δ8.02(d,J＝8.8Hz,2H),7.51(d,J＝8.4Hz,2H),7.16 (t,J＝7.2Hz,1H),7.05(dd,J＝7.2Hz,1.2Hz,1H),6.70(s,1H),6.80-6.74(m,2H), 6.30(d,J＝12.0Hz,1H),3.91(s,3H),3.70(dd,J＝14.4Hz,2.0Hz,1H),2.90(d,J ＝14.4Hz,1H),1.28(s,3H),1.19(s,3H).13C{1H}NMR(150MHz,CDCl3):δ176.0, 166.4,152.4(d,JC-F＝259.4Hz),146.2(d,JC-F＝1.8Hz),139.3,130.9,130.0, 129.3(d,JC-F＝2.0Hz),128.1(d,JC-F＝5.9Hz),125.9,118.7,116.7(d,JC-F＝7.1Hz), 110.0,104.7(d,JC-F＝14.9Hz),75.5(d,JC-F＝27.3Hz),52.3,49.0,40.8,26.0,22.6. 19FNMR(376MHz,CDCl3):δ-128.2(d,J＝10.9Hz).HRMS(ESI)m/z:[M+H]+ Calcd for C22H22FN2O3381.1609；Found381.1611.
5-Fluoro-2,2-dimethyl-4a-(4-nitrophenyl)-1,2,4,4a-tetrahydro-3H-pyrimido[1,2-a] quinolin-3-one(3z)
1H NMR(400MHz,CDCl3):δ8.20(d,J＝8.8Hz,2H),7.65(d,J＝8.8Hz,2H),7.49 (s,1H),7.19(t,J＝7.6Hz,1H),7.07(d,J＝6.8Hz,1H),6.83-6.78(m,2H),6.32(d, J＝12.4Hz,1H),3.76(d,J＝14.4Hz,1H),2.88(d,J＝14.4Hz,1H),1.28(s,3H), 1.20(s,3H).13C{1H}NMR(100MHz,CDCl3):δ176.3,152.0(d,JC-F＝261.3Hz), 148.4(d,JC-F＝1.8Hz),148.2,139.1,129.5(d,JC-F＝2.1Hz),128.2(d,JC-F＝6.2Hz), 127.0,123.9,119.1,116.6(d,JC-F＝7.1Hz),110.3,104.9(d,JC-F＝15.5Hz),75.2(d, JC-F＝26.9Hz),49.3,40.8,25.8,22.6.19FNMR(565MHz,CDCl3):δ-128.3(d,J＝ 11.9Hz).HRMS(ESI)m/z:[M+Na]+Calcdfor C20H18FN3NaO3390.1224；Found 390.1221.
5-Fluoro-2,2-dimethyl-4a-(m-tolyl)-1,2,4,4a-tetrahydro-3H-pyrimido[1,2-a]quino lin-3-one(3aa)
1H NMR(400MHz,CDCl3):δ7.25-7.21(m,3H),7.15-7.12(m,2H),7.03(d,J＝6.8Hz,1H),6.76-6.73(m,3H),6.25(d,J＝12.4Hz,1H),3.67(d,J＝14.4Hz,1H),2.98 (d,J＝14.4Hz,1H),2.32(s,3H),1.27(s,3H),1.19(s,3H).13C{1H}NMR(100 MHz,CDCl3):δ176.0,152.8(d,JC-F＝258.7Hz),141.6(d,JC-F＝1.7Hz),139.5, 138.5,129.8,129.1(d,JC-F＝1.9Hz),128.6,127.9(d,JC-F＝6.3Hz),126.4,123.0, 118.3,116.8(d,JC-F＝7.2Hz),109.8,104.2(d,JC-F＝15.5Hz),75.6(d,JC-F＝26.6 Hz),48.8,40.9,26.1,22.6,21.6.19FNMR(565MHz,CDCl3):δ-128.4(d,J＝12.4 Hz).HRMS(ESI)m/z:[M+H]+Calcd forC21H22FN2O337.1711；Found337.1710.
5-Fluoro-4a-(3-methoxyphenyl)-2,2-dimethyl-1,2,4,4a-tetrahydro-3H-pyrimido[1, 2-a]quinolin-3-one(3bb)
1H NMR(400MHz,CDCl3):δ7.29-7.25(m,1H),7.13(t,J＝8.0Hz,1H),7.03-6.98(m,2H),6.95(s,1H),6.87(dd,J＝8.4Hz,2.4Hz,1H),6.76-6.72(m,3H),6.26(d,J ＝12.4Hz,1H),3.74(s,3H),3.66(dd,J＝14.0Hz,1.6Hz,1H),3.00(d,J＝14.4Hz, 1H),1.27(s,3H),1.19(s,3H).13C{1H}NMR(150MHz,CDCl3):δ176.0,159.9, 152.8(d,JC-F＝259.2Hz),143.2,139.4,129.7,129.1(d,JC-F＝1.8Hz),127.9(d,JC-F＝6.2Hz),118.4,118.1,116.9(d,JC-F＝7.5Hz),114.0,112.0,109.9,104.3(d,JC-F＝ 15.5Hz),75.5(d,JC-F＝27.6Hz),55.3,48.9,40.8,26.0,22.7.19F NMR(565MHz, CDCl3):δ-128.5(d,J＝11.9Hz).HRMS(ESI)m/z:[M+Na]+Calcd for C21H21FN2 NaO2375.1479；Found375.1473.
5-Fluoro-4a-(3-fluorophenyl)-2,2-dimethyl-1,2,4,4a-tetrahydro-3H-pyrimido[1,2- a]quinolin-3-one(3cc)
1H NMR(600MHz,CDCl3):δ7.33-7.29(m,1H),7.23-7.21(m,2H),7.16-7.14(m,2H),7.04-7.01(m,2H),6.78-6.75(m,2H),6.27(d,J＝12.0Hz,1H),3.70(dd,J＝14.4Hz,1.8Hz,1H),2.96(d,J＝14.4Hz,1H),1.27(s,3H),2.00(s,3H).13C{1H} NMR(150MHz,CDCl3):δ176.1,163.0(d,JC-F＝246.9Hz),152.5(d,JC-F＝258.3 Hz),144.4(d,JC-F＝5.0Hz),139.3,130.2(d,JC-F＝8.0Hz),129.3(d,JC-F＝2.7Hz), 128.0(d,JC-F＝7.4Hz),121.5(d,JC-F＝1.7Hz),118.7,116.7(d,JC-F＝8.1Hz),116.1 (d,JC-F＝22.2Hz),113.2(d,JC-F＝21.2Hz),110.0,104.5(d,JC-F＝16.4Hz),75.2(d, JC-F＝27.3Hz),49.0,40.8,25.9,22.6.19F NMR(565MHz,CDCl3):δ-111.5–-111.6 (m),-128.4(d,J＝11.3Hz).HRMS(ESI)m/z:[M+H]+Calcd for C21H19F2N2O 341.1460；Found341.1459.
4a-(3-Chlorophenyl)-5-fluoro-2,2-dimethyl-1,2,4,4a-tetrahydro-3H-pyrimido[1,2- a]quinolin-3-one(3dd)
1H NMR(600MHz,CDCl3):δ7.52(s,1H),7.44(t,J＝1.8Hz,1H),7.34-7.32(m, 1H),7.30-7.29(m,1H),7.27-7.24(m,1H),7.15(t,J＝8.4Hz,1H),7.03(dd,J＝7.8 Hz,1.8Hz,1H),6.78-6.74(m,2H),6.26(d,J＝12.0Hz,1H),3.72(dd,J＝14.4Hz, 2.4Hz,1H),2.96(d,J＝14.4Hz,1H),1.26(s,3H),1.19(s,3H).13C{1H}NMR(100 MHz,CDCl3):δ176.2,152.3(d,JC-F＝260.0Hz),144.0(d,JC-F＝1.7Hz),139.3, 135.0,130.0,129.3(d,JC-F＝2.1Hz),129.2,128.1(d,JC-F＝6.1Hz),126.1,124.1, 118.7,116.7(d,JC-F＝7.4Hz),110.0,104.5(d,JC-F＝15.7Hz),75.2(d,JC-F＝26.8 Hz),49.0,40.8,25.9,22.6.19FNMR(565MHz,CDCl3):δ-127.9(d,J＝11.9Hz). HRMS(ESI)m/z:[M+Na]+Calcd for C20H18ClFN2NaO379.0984；Found379.0972.
4a-(3-Bromophenyl)-5-fluoro-2,2-dimethyl-1,2,4,4a-tetrahydro-3H-pyrimido[1,2- a]quinolin-3-one(3ee)
1H NMR(400MHz,CDCl3):δ7.58(d,J＝1.6Hz,1H),7.46(d,J＝7.6Hz,1H),7.37 (d,J＝8.0Hz,1H),7.23-7.19(m,2H),7.17-7.13(m,1H),7.03(d,J＝7.6Hz,1H), 6.78-6.74(m,2H),6.27(d,J＝12.0Hz,1H),3.72(dd,J＝14.4Hz,2.0Hz,1H),2.95 (d,J＝14.4Hz,1H),1.26(s,3H),1.20(s,3H).13C{1H}NMR(150MHz,CDCl3):δ 176.1,152.3(d,JC-F＝259.1Hz),144.2(d,JC-F＝2.0Hz),139.3,132.2,130.2,129.3 (d,JC-F＝2.9Hz),129.0,128.1(d,JC-F＝7.4Hz),124.6,123.1,118.7,116.6(d,JC-F＝ 7.4Hz),110.1,104.6(d,JC-F＝15.0Hz),75.2(d,JC-F＝27.2Hz),49.0,40.9,26.0, 22.7.19FNMR(565MHz,CDCl3):δ-128.1(d,J＝12.4Hz).HRMS(ESI)m/z: [M+Na]+Calcd for C20H18BrFN2NaO 423.0479；Found423.0476.
5-Fluoro-2,2-dimethyl-4a-(3-nitrophenyl)-1,2,4,4a-tetrahydro-3H-pyrimido[1,2-a] quinolin-3-one(3ff)
1H NMR(400MHz,CDCl3):δ8.34(s,1H),8.19(d,J＝8.0Hz,1H),8.00(s,1H), 7.82(d,J＝7.6Hz,1H),7.54(t,J＝8.0Hz,1H),7.18(t,J＝8.0Hz,1H),7.06(d,J＝ 7.2Hz,1H),6.83-6.78(m,2H),6.32(d,J＝12.0Hz,1H),3.79(d,J＝14.4Hz,1H), 2.96(d,J＝14.4Hz,1H),1.28(s,3H),1.20(s,3H).13C{1H}NMR(100MHz, CDCl3):δ176.4,152.0(d,JC-F＝260.3Hz),148.5,144.3(d,JC-F＝1.5Hz),139.2, 131.8,129.9,129.5(d,JC-F＝2.7Hz),128.2(d,JC-F＝5.6Hz),124.0,120.9,119.1, 116.6(d,JC-F＝7.2Hz),110.4,104.9(d,JC-F＝15.5Hz),75.1(d,JC-F＝26.7Hz),49.2, 40.8,25.8,22.5.19FNMR(565MHz,CDCl3):δ-127.7(d,J＝11.9Hz).HRMS(ESI) m/z:[M+Na]+Calcd for C20H18FN3NaO3390.1224；Found390.1218.
4a-(3,5-Dimethoxyphenyl)-5-fluoro-2,2-dimethyl-1,2,4,4a-tetrahydro-3H-pyrimid o[1,2-a]quinolin-3-one(3gg)
1H NMR(400MHz,CDCl3):δ7.12(t,J＝6.8Hz,1H),7.01(dd,J＝8.0Hz,1.6Hz, 1H),6.88(s,1H),6.75-6.71(m,2H),6.56(d,J＝2.0Hz,2H),6.42(t,J＝2.4Hz,1H), 6.25(d,J＝12.4Hz,1H),3.71(s,6H),3.67(dd,J＝14.4Hz,2.0Hz,1H),3.04(d,J＝ 14.0Hz,1H),1.26(s,3H),1.19(s,3H).13C{1H}NMR(150MHz,CDCl3):δ176.1, 161.1,152.8(d,JC-F＝259.8Hz),144.1(d,JC-F＝2.4Hz),139.4,129.1(d,JC-F＝2.3 Hz),127.9(d,JC-F＝7.1Hz),118.4,116.9(d,JC-F＝7.8Hz),110.0,104.4,104.2(d, JC-F＝15.6Hz),100.3,75.5(d,JC-F＝26.3Hz),55.4,49.0,40.8,26.0,22.7.19F NMR (376MHz,CDCl3):δ-128.8(d,J＝10.9Hz).HRMS(ESI)m/z:[M+H]+Calcd for C22H24FN2O3 383.1765；Found383.1762.
5-Fluoro-4a-(2-fluorophenyl)-2,2-dimethyl-1,2,4,4a-tetrahydro-3H-pyrimido[1,2- a]quinolin-3-one(3hh)`
1H NMR(600MHz,CDCl3):δ7.38(td,J＝7.8Hz,1.2Hz,1H),7.35-7.32(m,1H), 7.16(t,J＝8.4Hz,1H),7.11(t,J＝7.8Hz,1H),7.09-7.06(m,1H),7.01(dd,J＝7.2 Hz,1.2Hz,1H),6.95(s,1H),6.81(d,J＝7.8Hz,1H),6.75(t,J＝7.8Hz,1H),6.21 (d,J＝12.0Hz,1H),3.81(d,J＝14.4Hz,1H),3.06(d,J＝13.8Hz,1H),1.25(s,3H), 1.18(s,3H).13C{1H}NMR(150MHz,CDCl3):δ175.7,160.1(d,JC-F＝248.3Hz), 151.2(d,JC-F＝259.8Hz),139.5,131.2(d,JC-F＝9.0Hz),129.1(d,JC-F＝2.1Hz), 128.2(dd,JC-F＝10.1Hz,2.3Hz),128.01,127.99(d,JC-F＝5.7Hz),124.2(d,JC-F＝3.2Hz),118.5,117.4(d,JC-F＝23.0Hz),117.0(d,JC-F＝7.5Hz),109.7,104.3(d,JC-F＝15.9Hz),74.4(d,JC-F＝27.2Hz),49.5,41.0,25.7,22.4.19F NMR(565MHz, CDCl3):δ-111.56–-111.62(m),-129.1(t,J＝12.4Hz).HRMS(ESI)m/z:[M+H]+ Calcd for C20H19F2N2O 341.1460；Found 341.1460.
5-Fluoro-2,2-dimethyl-4a-(naphthalen-2-yl)-1,2,4,4a-tetrahydro-3H-pyrimido[1,2 -a]quinolin-3-one(3ii)
1H NMR(400MHz,CDCl3):δ7.88-7.79(m,4H),7.53-7.47(m,3H),7.16(t,J＝8.4Hz,1H),7.07(dd,J＝7.2Hz,1.2Hz,1H),6.86(s,1H),6.79-6.75(m,2H),6.32(d,J ＝12.0Hz,1H),3.68(d,J＝14.4Hz,2.0Hz,1H),2.99(d,J＝14.4Hz,1H),1.30(s, 3H),1.19(s,3H).13C{1H}NMR(150MHz,CDCl3):δ176.2,152.5(d,JC-F＝259.8 Hz),139.5,138.8(d,JC-F＝2.0Hz),133.4,132.5,129.3(d,JC-F＝1.7Hz),129.2, 128.7,128.1(d,JC-F＝5.4Hz),127.6,127.0,126.8,124.9,123.4,118.4,116.8(d,JC-F＝6.9Hz),109.9,104.6(d,JC-F＝15.8Hz),75.8(d,JC-F＝27.3Hz),48.8,41.0,26.1, 22.6.19F NMR(565MHz,CDCl3):δ-128.6(d,J＝10.2Hz).HRMS(ESI)m/z: [M+H]+Calcd for C24H22FN2O 373.1711；Found 373.1717.
5-Fluoro-2,2-dimethyl-4a-(thiophen-3-yl)-1,2,4,4a-tetrahydro-3H-pyrimido[1,2-a] quinolin-3-one(3jj)
1H NMR(400MHz,CDCl3):δ7.26-7.23(m,2H),7.14(t,J＝8.4Hz,1H),7.03(d,J ＝7.2Hz,1H),6.97(s,1H),6.90(dd,J＝4.8Hz,1.6Hz,1H),6.77(t,J＝7.2Hz,1H), 6.71(d,J＝8.4Hz,1H),6.24(d,J＝12.0Hz,1H),3.63(d,J＝14.0Hz,2.0Hz,1H), 3.06(d,J＝13.6Hz,1H),1.28(s,3H),1.22(s,3H).13C{1H}NMR(100MHz, CDCl3):δ175.8,153.3(d,JC-F＝261.1Hz),142.8(d,JC-F＝1.8Hz),139.3,129.0(d, JC-F＝2.6Hz),127.7(d,JC-F＝5.6Hz),127.3,125.4,123.1,118.8,117.7(d,JC-F＝8.2 Hz),110.4,103.7(d,JC-F＝15.9Hz),73.5(d,JC-F＝26.1Hz),49.1,40.5,26.0,22.6. 19F NMR(565MHz,CDCl3):δ-128.3(d,J＝13.0Hz).HRMS(ESI)m/z:[M+Na]+ Calcd for C18H17FN2NaOS 351.0938；Found351.0930.
实施例4
本发明所合成产物氟代吡啶并嘧啶酮类化合物3可进行一系列反应，从而合成多种有价值的喹啉类化合物。例如：
Figure BDA0003824153500000191
在25mL圆底烧瓶中加入3a(32.2mg,0.1mmol)、劳森试剂(32.4mg,0.08 mmol)和甲苯(2mL)，随后将体系回流反应12小时，反应结束后，缓慢加入饱和氯化铵溶液淬灭反应。用乙醚萃取，有机相水洗、干燥、过滤、浓缩，过硅胶柱分离(石油醚/乙酸乙酯＝30/1)得白色固体产物4a(16.3mg,73％)。该化合物的表征数据如下：1H NMR(600MHz,CDCl3):δ8.08(d,J＝9.0Hz,1H), 7.99-7.98(m,2H),7.75(d,J＝10.8Hz,1H),7.69(d,J＝8.4Hz,1H),7.59(t,J＝8.4 Hz,1H),7.46-7.43(m,3H),7.41-7.38(m,1H).13C{1H}NMR(150MHz,CDCl3):δ 155.1(d,JC-F＝259.4Hz),149.2(d,JC-F＝13.5Hz),145.3(d,JC-F＝2.3Hz),135.8(d, JC-F＝4.7Hz),129.7(d,JC-F＝5.9Hz),129.4(d,JC-F＝6.0Hz),128.8(d,JC-F＝3.2 Hz),128.6,128.3(d,JC-F＝5.9Hz),127.4,126.8(d,JC-F＝4.5Hz),119.7(d,JC-F＝ 20.3Hz).19F NMR(565MHz,CDCl3):δ-124.4(d,J＝10.7Hz).HRMS(ESI)m/z: [M+H]+Calcd for C15H11FN224.0870；Found 224.0866.
实施例5
依照实施例4的方法和步骤a,b，通过改变反应物3，可以合成出各种氟代喹啉类化合物4，具体结果如下：
Figure BDA0003824153500000192
a反应条件：3(0.1mmol),LR(0.08mmol),甲苯(2mL),回流12h,空气氛围；b分离收率。
代表性产物表征数据如下： 3-Fluoro-6-methyl-2-phenylquinoline(4b)：1HNMR(400MHz,CDCl3):δ 8.07-8.04(m,3H),7.74(d,J＝11.2Hz,1H),7.54-7.47(m,5H),2.53(s,3H).13C{1H} NMR(100MHz,CDCl3):δ155.3(d,JC-F＝259.5Hz),148.1(d,JC-F＝14.3Hz),143.9(d,JC-F＝2.9Hz),137.4,135.9(d,JC-F＝5.4Hz),131.1(d,JC-F＝2.5Hz),129.4,129.3(d,JC-F＝3.7Hz),129.2,128.5,128.4(d,JC-F＝4.6Hz),125.6(d,JC-F＝4.7Hz),119.1(d,JC-F＝19.4Hz),21.7.19F NMR(376MHz,CDCl3):δ-124.8(d,J＝10.9 Hz).HRMS(ESI)m/z:[M+H]+Calcd for C16H13FN 238.1027；Found 238.1029.
6-Bromo-3-fluoro-2-phenylquinoline(4c)：1H NMR(600MHz,CDCl3):δ8.06(d, J＝7.2Hz,2H),8.00(d,J＝9.6Hz,1H),7.93(s,1H),7.74-7.73(m,2H),7.53-7.50 (m,3H).13C{1H}NMR(150MHz,CDCl3):δ155.5(d,JC-F＝261.2Hz),149.5(d, JC-F＝14.3Hz),143.8(d,JC-F＝2.9Hz),135.3(d,JC-F＝4.8Hz),132.4(d,JC-F＝1.8 Hz),131.3,129.9,129.4(d,JC-F＝5.9Hz),129.3(d,JC-F＝5.7Hz),128.8(d,JC-F＝ 3.9Hz),128.6,121.5,118.8(d,JC-F＝21.0Hz).19F NMR(565MHz,CDCl3):δ -122.6(d,J＝9.0Hz).HRMS(ESI)m/z:[M+H]+Calcdfor C15H10BrFN 301.9975； Found 301.9969.
3-Fluoro-2-(p-tolyl)quinoline(4d)：1H NMR(600MHz,CDCl3):δ8.08(d,J＝8.4Hz,1H),7.91(dd,J＝8.4Hz,1.8Hz,2H),7.75(d,J＝11.4Hz,1H),7.70(d,J＝7.8 Hz,1H),7.60(t,J＝8.4Hz,1H),7.46(t,J＝7.2Hz,1H),7.26(d,J＝8.4Hz,2H), 2.36(s,3H).13C{1H}NMR(150MHz,CDCl3):δ155.1(d,JC-F＝259.1Hz),149.2(d, JC-F＝14.4Hz),145.3(d,JC-F＝3.0Hz),139.8,133.0(d,JC-F＝3.8Hz),129.6,129.3, 129.2(d,JC-F＝5.6Hz),128.7(d,JC-F＝2.1Hz),128.2(d,JC-F＝5.7Hz),127.2,126.8 (d,JC-F＝3.9Hz),119.6(d,JC-F＝20.4Hz),21.5.19F NMR(565MHz,CDCl3):δ -124.2(d,J＝10.7Hz).HRMS(ESI)m/z:[M+H]+Calcd for C16H13FN 238.1027； Found 238.1032.
2-(4-Bromophenyl)-3-fluoroquinoline(4e)：1H NMR(600MHz,CDCl3):δ8.14(d,J＝8.4Hz,1H),7.98(dd,J＝8.4Hz,1.8Hz,2H),7.85(d,J＝11.4Hz,1H),7.79(d, J＝8.4Hz,1H),7.69(t,J＝7.2Hz,1H),7.66-7.64(m,2H),7.56(t,J＝7.2Hz,1H). 13C{1H}NMR(100MHz,CDCl3):δ155.0(d,JC-F＝258.9Hz),147.7(d,JC-F＝13.4 Hz),145.2(d,JC-F＝3.0Hz),134.6(d,JC-F＝5.1Hz),131.8,130.9(d,JC-F＝5.8Hz), 129.6,129.0(d,JC-F＝2.0Hz),128.4(d,JC-F＝5.2Hz),127.6,126.8(d,JC-F＝4.8Hz), 124.3,119.9(d,JC-F＝19.9Hz).19F NMR(565MHz,CDCl3):δ-124.3(d,J＝11.3 Hz).HRMS(ESI)m/z:[M+H]+Calcdfor C15H10BrFN 301.9975；Found301.9979.
2-([1,1'-Biphenyl]-4-yl)-3-fluoroquinoline(4f)：1H NMR(600MHz,CDCl3):δ8.19-8.17(m,3H),7.86(d,J＝11.4Hz,1H),7.79(d,J＝8.4Hz,1H),7.76(d,J＝8.4 Hz,2H),7.70-7.67(m,3H),7.55(t,J＝7.8Hz,1H),7.47(t,J＝7.8Hz,2H),7.38(t, J＝7.2Hz,1H).13C{1H}NMR(100MHz,CDCl3):δ155.2(d,JC-F＝258.9Hz), 148.7(d,JC-F＝14.7Hz),145.3(d,JC-F＝2.9Hz),142.4,140.6,134.7(d,JC-F＝4.9 Hz),129.8(d,JC-F＝5.4Hz),129.7,128.9,128.8(d,JC-F＝2.0Hz),128.3(d,JC-F＝ 4.6Hz),127.7,127.4,127.30,127.26,126.8(d,JC-F＝5.7Hz),119.7(d,JC-F＝18.6 Hz).19FNMR(565MHz,CDCl3):δ-124.2(d,J＝9.0Hz).HRMS(ESI)m/z: [M+H]+Calcd for C21H15FN 300.1183；Found300.1178.
3-Fluoro-2-(4-nitrophenyl)quinoline(4g)：1H NMR(600MHz,CDCl3):δ8.38-8.36 (m,2H),8.30(dd,J＝9.0Hz,1.2Hz,2H),8.18(d,J＝8.4Hz,1H),7.93(d,J＝11.4 Hz,1H),7.84(d,J＝8.4Hz,1H),7.74(td,J＝7.2Hz,1.2Hz,,1H),7.62(t,J＝7.2 Hz,1H).13C{1H}NMR(150MHz,CDCl3):δ155.1(d,JC-F＝260.7Hz),148.4,146.1 (d,JC-F＝14.7Hz),145.3(d,JC-F＝2.1Hz),141.7(d,JC-F＝5.6Hz),130.3(d,JC-F＝ 4.7Hz),129.9,129.4(d,JC-F＝1.5Hz),128.8(d,JC-F＝5.4Hz),128.3,126.9(d,JC-F＝5.1Hz),123.7,120.4(d,JC-F＝19.7Hz).19F NMR(565MHz,CDCl3):δ-124.4(d, J＝11.3Hz).HRMS(ESI)m/z:[M+H]+Calcdfor C15H10FN2O2269.0721；Found 269.0724.
Methyl4-(3-fluoroquinolin-2-yl)benzoate(4h)：1H NMR(600MHz,CDCl3):δ8.20-8.16(m,5H),7.88(d,J＝11.4Hz,1H),7.81(d,J＝7.8Hz,1H),7.71(t,J＝7.2 Hz,1H),7.58(t,J＝7.2Hz,1H),3.96(s,3H).13C{1H}NMR(150MHz,CDCl3):δ 166.9,155.1(d,JC-F＝258.2Hz),147.8(d,JC-F＝14.3Hz),145.3(d,JC-F＝3.0Hz), 139.9(d,JC-F＝6.2Hz),130.9,129.8,129.7,129.3(d,JC-F＝5.3Hz),129.0(d,JC-F＝ 3.3Hz),128.6(d,JC-F＝5.4Hz),127.8,126.9(d,JC-F＝3.8Hz),120.0(d,JC-F＝19.7 Hz),52.3.19F NMR(565MHz,CDCl3):δ-124.3(d,J＝13.0Hz).HRMS(ESI)m/z: [M+H]+Calcd for C17H13FNO2282.0925；Found282.0924.
以上实施例描述了本发明的基本原理、主要特征及优点。本行业的技术人员应该了解，本发明不受上述实施例的限制，上述实施例和说明书中描述的只是说明本发明的原理，在不脱离本发明原理的范围下，本发明还会有各种变化和改进，这些变化和改进均落入本发明保护的范围内。

Claims (8)

1.氟代吡啶并嘧啶酮类化合物，其特征在于，结构通式为：
Figure FDA0003824153490000011
其中，R1为C1-4烷基、C1-4烷氧基、苄氧基、卤素、氰基或三氟甲基，R2为苯基、取代苯基、萘基或噻吩基，取代苯基苯环上的取代基为一元或多元取代C1-4烷基、C1-4烷氧基、苯基、卤素、氰基、三氟甲基、C1-4烷氧羰基或硝基。
2.如权利要求1所述氟代吡啶并嘧啶酮类化合物的合成方法，其特征在于，包括如下操作：以1-芳基取代吡唑烷酮类化合物1和偕二氟环丙烯类化合物2为原料，在铑催化剂和醋酸盐添加剂存在下，有机溶剂中升温反应，得到氟代吡啶并嘧啶酮类化合物3；反应方程式表示为：
Figure FDA0003824153490000012
其中，R1为C1-4烷基、C1-4烷氧基、苄氧基、卤素、氰基或三氟甲基，R2为苯基、取代苯基、萘基或噻吩基，取代苯基苯环上的取代基为一元或多元取代的C1-4烷基、C1-4烷氧基、苯基、卤素、氰基、三氟甲基、C1-4烷氧羰基或硝基。
3.根据权利要求2所述氟代吡啶并嘧啶酮类化合物的合成方法，其特征在于：所述铑催化剂为[RhCp*Cl2]2或[RhCp*(MeCN)3](SbF6)2。
4.根据权利要求2所述氟代吡啶并嘧啶酮类化合物的合成方法，其特征在于：所述醋酸盐添加剂为醋酸钠、醋酸钾或醋酸铯。
5.根据权利要求2所述氟代吡啶并嘧啶酮类化合物的合成方法，其特征在于：所述有机溶剂选自二氯乙烷、二氯甲烷、乙腈、四氢呋喃、乙酸乙酯、甲苯或1,4-二氧六环。
6.根据权利要求2所述氟代吡啶并嘧啶酮类化合物的合成方法，其特征在于：所述1-芳基取代吡唑烷酮类化合物1、偕二氟环丙烯类化合物2、铑催化剂与醋酸盐添加剂摩尔比为1.5-2:1-1.2:0.025-0.05:1-2。
7.根据权利要求2所述氟代吡啶并嘧啶酮类化合物的合成方法，其特征在于：
反应温度为60-80℃。
8.根据权利要求2-7任意一项所述氟代吡啶并嘧啶酮类化合物的合成方法，其特征在于：反应在空气中进行。
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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5962457A (en) * 1996-05-15 1999-10-05 Pfizer Inc. 2,3 Disubstituted- (5,6)-heteroarylfused-pyrimidine-4-ones
US20110034334A1 (en) * 2008-01-17 2011-02-10 Syngenta Crop Protection, Inc. Herbicidal compounds
CN101985448A (zh) * 2010-12-03 2011-03-16 西北师范大学 药物中间体吡啶[2,3-d]嘧啶-4(3H)-酮及其制备
CN104672131A (zh) * 2013-11-27 2015-06-03 中国科学院大连化学物理研究所 一种合成3-氟喹啉衍生物的方法
WO2019015593A1 (zh) * 2017-07-19 2019-01-24 江苏奥赛康药业股份有限公司 嘧啶并吡啶酮或者吡啶并吡啶酮类化合物及其应用
CN112759589A (zh) * 2019-11-01 2021-05-07 暨南大学 嘧啶并吡啶酮类化合物及其应用

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5962457A (en) * 1996-05-15 1999-10-05 Pfizer Inc. 2,3 Disubstituted- (5,6)-heteroarylfused-pyrimidine-4-ones
US20110034334A1 (en) * 2008-01-17 2011-02-10 Syngenta Crop Protection, Inc. Herbicidal compounds
CN101985448A (zh) * 2010-12-03 2011-03-16 西北师范大学 药物中间体吡啶[2,3-d]嘧啶-4(3H)-酮及其制备
CN104672131A (zh) * 2013-11-27 2015-06-03 中国科学院大连化学物理研究所 一种合成3-氟喹啉衍生物的方法
WO2019015593A1 (zh) * 2017-07-19 2019-01-24 江苏奥赛康药业股份有限公司 嘧啶并吡啶酮或者吡啶并吡啶酮类化合物及其应用
CN112759589A (zh) * 2019-11-01 2021-05-07 暨南大学 嘧啶并吡啶酮类化合物及其应用

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
MENGYANG SHEN，ET AL.: "Rh(III)-catalyzed simultaneous [3 + 3]/[5 + 1] annulation of 1-arylpyrazolidinones with gemdifluorocyclopropenes leading to fluorinated pyridopyrimidinone derivatives", 《ORG. CHEM. FRONT.》, vol. 9, pages 5976 - 5982 *

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