氟代吡啶并嘧啶酮类化合物及其合成方法

1.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：

2.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。
3.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。
4.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。


技术实现要素：

5.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。
6.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：
[0007][0008]
其中，r1为c
1-4
烷基、c
1-4
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c
1-4
烷基、c
1-4
烷氧基、苯基、卤素、氰基、三氟甲基、c
1-4
烷氧羰基或硝基。
[0009]
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：
[0010]
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。
[0011]
反应方程式为：
[0012][0013]
其中，r1为c
1-4
烷基、c
1-4
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c
1-4
烷基、c
1-4
烷氧基、苯基、卤素、氰基、三氟甲基、c
1-4
烷氧羰基或硝基。
[0014]
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)。
[0015]
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。
[0016]
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。
[0017]
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。
[0018]
进一步地，在上述技术方案中，所述反应温度为60-80℃。
[0019]
进一步地，在上述技术方案中，所述反应在空气氛围下进行。
[0020]
发明有益效果：
[0021]
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
[0022][0023]
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
[0024]
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。
[0025]
实施例1
[0026][0027]
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。
[0028]
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。
[0029]
表1不同条件下3a的合成a[0030][0031][0032]
实施例2
[0033][0034]
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).
13
c{1h}nmr(100mhz,cdcl3):δ 176.2,152.9(d,j
c-f
＝259.1hz),141.5(d,j
c-f
＝2.3hz),139.4,129.13(d,j
c-f
＝3.0 hz),129.08,128.7,127.9(d,j
c-f
＝5.3hz),125.8,118.4,116.9(d,j
c-f
＝6.7hz), 109.9,104.3(d,j
c-f
＝16.4hz),75.6(d,j
c-f
＝26.6hz),48.8(d,j
c-f
＝2.1hz),40.8, 26.0,22.6.
19
f nmr(376mhz,cdcl3):δ-128.4(d,j＝12.4hz).hrms(esi)m/z: [m h]

calcd for c
20h20
fn2o 323.1554；found 323.1549.
[0035]
实施例3
[0036]
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：
[0037][0038]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。
[0039]
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)
[0040]1h nmr(400mhz,cdcl3):δ7.41-7.39(m,2h),7.35-7.32(m,3h),6.94(d,j＝8.4 hz,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).
13
c{1h}nmr(100mhz,cdcl3):δ176.2,153.2(d,j
c-f
＝258.9hz),141.5(d, j
c-f
＝1.8hz),137.3,129.6(d,j
c-f
＝1.9hz),129.0,128.7,128.4(d,j
c-f
＝5.3hz) 127.6,125.8,116.9(d,j
c-f
＝6.8hz),110.0,104.2(d,j
c-f
＝15.8hz),75.6(d,j
c-f
＝ 26.1hz),49.0(d,j
c-f
＝1.4hz),40.8,26.1,22.6,20.2.
19
f nmr(376mhz,cdcl3): δ-128.2(d,j＝12.8hz).hrms(esi)m/z:
[m h]

calcd for c
21h22
fn2o 337.1711； found 337.1704.
[0041]
8-ethyl-5-fluoro-2,2-dimethyl-4a-phenyl-4,4a-dihydro-1h-pyrimido[1,2-a]quinol in-3(2h)-one(3c)
[0042]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). 13
c{1h}nmr(100mhz,cdcl3):δ176.1,153.1(d,j
c-f
＝259.3hz),141.6(d,j
c-f
＝1.7hz),137.5,134.1,129.0,128.7,128.4(d,j
c-f
＝2.1hz),127.2(d,j
c-f
＝5.9hz), 125.8,116.9(d,j
c-f
＝8.0hz),109.9,104.4(d,j
c-f
＝15.9hz),75.6(d,j
c-f
＝26.5 hz),48.9(d,j
c-f
＝2.1hz),40.8,27.6,26.1,22.6,15.6.
19
f nmr(376mhz,cdcl3): δ-128.6(d,j＝9.8hz).hrms(esi)m/z:[m h]

calcd for c
22h24
fn2o 351.1867； found 351.1845.
[0043]
5-fluoro-8-isopropyl-2,2-dimethyl-4a-phenyl-1,2,4,4a-tetrahydro-3h-pyrimido[1, 2-a]quinolin-3-one(3d)
[0044]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).
13
c{1h} nmr(150mhz,cdcl3):δ176.1,152.9(d,j
c-f
＝258.8hz),141.6,138.8,137.5, 129.0,128.7,127.0(d,j
c-f
＝2.1hz),125.9(d,j
c-f
＝4.8hz),125.8,116.7(d,j
c-f
＝ 5.3hz),109.8,104.5(d,j
c-f
＝15.6hz),75.7(d,j
c-f
＝27.3hz),48.9,40.8,32.9, 26.2,24.1,24.0,22.7.
19
f nmr(565mhz,cdcl3):δ-128.9(d,j＝12.4hz).hrms (esi)m/z:[m na]

calcdforc
23h25
fn2nao387.1843；found387.1838.
[0045]
8-(benzyloxy)-5-fluoro-2,2-dimethyl-4a-phenyl-1,2,4,4a-tetrahydro-3h-pyrimido [1,2-a]quinolin-3-one(3e)
[0046]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).
13
c{1h}nmr(100mhz,cdcl3):δ176.1,154.1(d,j
c-f
＝261.6hz),151.7, 141.0(d,j
c-f
＝1.9hz),137.3,134.0,129.1,128.7,128.6,128.0,127.5,125.8,118.4 (d,j
c-f
＝7.2hz),115.3(d,j
c-f
＝2.7hz),114.4(d,j
c-f
＝6.2hz),111.3,104.4(d, j
c-f
＝16.8hz),75.6(d,j
c-f
＝25.7hz),70.8,49.5,40.6,26.2,22.7.
19
fnmr(376 mhz,cdcl3):δ-126.5(d,j＝12.4hz).hrms(esi)m/z:[m h]

calcdforc
27h26 fn2o2429.1973；found429.1979.
[0047]
5,8-difluoro-2,2-dimethyl-4a-phenyl-4,4a-dihydro-1h-pyrimido[1,2-a]quinolin-3 (2h)-one(3f)
[0048]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).
13
c{1h}nmr(100mhz,cdcl3):δ175.9,155.9(d,j
c-f
＝ 235.4hz),154.3(d,j
c-f
＝
261.9hz),140.9(d,j
c-f
＝2.1hz),135.8(d,j
c-f
＝1.8hz), 129.2,128.8,125.9,118.5(t,j
c-f
＝8.0hz),115.1(dd,j
c-f
＝22.2hz,2.9hz),114.1 (dd,j
c-f
＝24.1hz,6.9hz),111.1(d,j
c-f
＝7.2hz),103.8(dd,j
c-f
＝17.6hz,2.3 hz),75.5(d,j
c-f
＝27.2hz),49.5(d,j
c-f
＝1.3hz),40.7,26.0,22.6.
19
fnmr(376 mhz,cdcl3):δ-125.6(d,j＝10.9hz),-127.0(td,j＝8.6hz,3.8hz).hrms(esi) m/z:[m h]

calcdforc
20h19
f2n2o341.1460；found341.1456.
[0049]
8-chloro-5-fluoro-2,2-dimethyl-4a-phenyl-4,4a-dihydro-1h-pyrimido[1,2-a]quin olin-3(2h)-one(3g)
[0050]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).
13
c{1h}nmr(100mhz,cdcl3):δ175.9,153.8(d,j
c-f
＝262.4hz),141.1 (d,j
c-f
＝2.4hz),138.1,129.3,128.8,128.6(d,j
c-f
＝2.5hz),127.2(d,j
c-f
＝5.8 hz),125.7,123.0,118.6(d,j
c-f
＝8.5hz),111.2,103.5(d,j
c-f
＝16.2hz),75.4(d, j
c-f
＝26.3hz),49.2(d,j
c-f
＝2.3hz),40.8,25.9,22.5.
19
f nmr(565mhz,cdcl3): δ-125.9(d,j＝13.0hz).hrms(esi)m/z:[m na]

calcdforc
20h18
clfn2nao 379.0984；found379.0968.
[0051]
8-bromo-5-fluoro-2,2-dimethyl-4a-phenyl-1,2,4,4a-tetrahydro-3h-pyrimido[1,2
‑ꢀ
a]quinolin-3-one(3h)
[0052]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).
13
c{1h}nmr(100mhz,cdcl3):δ175.8,153.6(d,j
c-f
＝261.8hz),141.1 (d,j
c-f
＝2.1hz),138.5,131.5(d,j
c-f
＝1.8hz),130.0(d,j
c-f
＝6.1hz),129.3, 128.8,125.7,119.0(d,j
c-f
＝8.1hz),111.6,110.0,103.4(d,j
c-f
＝18.0hz),75.4(d, j
c-f
＝27.1hz),49.1,40.8,25.9,22.5.
19
f nmr(565mhz,cdcl3):δ-125.9(d,j＝ 10.2hz).hrms(esi)m/z:[m na]

calcdforc
20h18
brfn2nao423.0479；found 423.0467.
[0053]
5-fluoro-2,2-dimethyl-3-oxo-4a-phenyl-2,3,4,4a-tetrahydro-1h-pyrimido[1,2-a]q uinoline-8-carbonitrile(3i)
[0054]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).
13
c{1h}nmr(100mhz, cdcl3):δ175.3,153.4(d,j
c-f
＝261.2hz),142.4,140.9(d,j
c-f
＝2.0hz),133.4(d, j
c-f
＝2.2hz),131.3(d,j
c-f
＝6.5hz),129.7,129.0,125.6,119.2,117.4(d,j
c-f
＝8.1 hz),110.1,103.1(d,j
c-f
＝17.4hz),101.0,75.4(d,j
c-f
＝27.0hz),49.1(d,j
c-f
＝ 1.3hz),41.1,25.7,22.5.
19
fnmr(376mhz,cdcl3):δ-125.4(d,j＝13.9hz). hrms(esi)m/z:[m na]

calcd for c
21h18
fn3nao2370.1326；found370.1302.
[0055]
5-fluoro-2,2-dimethyl-4a-phenyl-8-(trifluoromethyl)-1,2,4,4a-tetrahydro-3h-pyr imido[1,2-a]quinolin-3-one(3j)
[0056]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).
13
c{1h}nmr(150mhz,cdcl3):δ175.6,153.4(d,j
c-f
＝260.6hz),141.8,141.2(d,j
c-f
＝2.3hz),129.4,128.9,125.7,125.6(q,j
c-f
＝211.4hz),125.3,123.5,120.4(q,j
c-f
＝32.1hz),116.8(d,j
c-f
＝9.6hz),109.5,103.6(d,j
c-f
＝16.7hz),75.5(d,j
c-f
＝28.1hz),49.1,41.0,25.8,22.5.
19
fnmr(376mhz,cdcl3):δ-61.5(s),-126.2(d,j＝9.8hz).hrms(esi)m/z:[m na]

calcdforc
21h18
f4n2nao2413.1247；found413.1229.
[0057]
5-fluoro-2,2,9-trimethyl-4a-phenyl-1,2,4,4a-tetrahydro-3h-pyrimido[1,2-a]quinolin-3-one(3k)
[0058]1hnmr(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).
13
c{1h}nmr(150mhz,cdcl3):δ176.1,152.4(d,j
c-f
＝243.2hz),141.6,139.4,139.1(d,j
c-f
＝2.4hz),129.0,128.7,127.7(d,j
c-f
＝5.0hz),125.7,119.3,114.4(d,j
c-f
＝8.0hz),110.7,104.2(d,j
c-f
＝15.9hz),75.6(d,j
c-f
＝26.4hz),48.8,40.8,26.0,22.6,22.0.
19
fnmr(376mhz,cdcl3):δ-130.1(d,j＝13.2hz).hrms(esi)m/z:[m na]

calcdforc
21h21
fn2nao359.1530；found359.1525.
[0059]
5-fluoro-9-methoxy-2,2-dimethyl-4a-phenyl-1,2,4,4a-tetrahydro-3h-pyrimido[1,2-a]quinolin-3-one(3l)
[0060]1hnmr(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).
13
c{1h}nmr(100mhz,cdcl3):δ175.9,160.9(d,j
c-f
＝2.3hz),151.6(d,j
c-f
＝255.8hz),141.7(d,j
c-f
＝2.3hz),140.8,129.0,128.7,128.6,125.7,110.4(d,j
c-f
＝7.3hz),103.8(d,j
c-f
＝16.8hz),102.4,97.6,75.4(d,j
c-f
＝26.6hz),55.3,49.0(d,j
c-f
＝1.8hz),40.8,26.0,22.6.
19
fnmr(376mhz,cdcl3):δ-132.4(d,j＝12.8hz).hrms(esi)m/z:[m na]

calcdforc
21h21
fn2nao2375.1479；found375.1473.
[0061]
9-chloro-5-fluoro-2,2-dimethyl-4a-phenyl-1,2,4,4a-tetrahydro-3h-pyrimido[1,2-a]quinolin-3-one(3m)
[0062]1hnmr(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).
13
c{1h}nmr(150mhz,cdcl3):δ175.8,153.0(d,j
c-f
＝260.0hz),141.2(d,j
c-f
＝2.1hz),140.4,134.6(d,j
c-f
＝3.9hz),129.3,128.8,128.7(d,j
c-f
＝6.0hz),125.7,118.4,115.6(d,j
c-f
＝9.2hz),110.2,103.5(d,j
c-f
＝18.0hz),75.3(d,j
c-f
＝25.5hz),49.1,40.8,25.9,22.5.
19
fnmr(565mhz,cdcl3):δ-127.7(d,j＝12.4hz).hrms(esi)m/z:[m na]

calcdforc
20h18
clfn2nao379.0984；found379.0966.
[0063]
9-bromo-5-fluoro-2,2-dimethyl-4a-phenyl-1,2,4,4a-tetrahydro-3h-pyrimido[1,2-a]quinolin-3-one(3n)
[0064]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).
13
c{1h}nmr(100mhz,cdcl3):δ175.7,153.1(d,j
c-f
＝260.8hz),141.1(d,j
c-f
＝2.6hz),140.5,129.3,128.9(d,j
c-f
＝5.9hz),128.8,125.6,122.7(d,j
c-f
＝2.6hz),121.4,116.1(d,j
c-f
＝7.7hz),113.1,103.6(d,j
c-f
＝16.3hz),75.3(d,j
c-f
＝26.8hz),49.1(d,j
c-f
＝2.1hz),40.8,25.9,22.5.
19
fnmr(376mhz,cdcl3):δ-127.3(d,j＝10.9hz).hrms(esi)m/z:[m na]

calcdforc
20h18
brfn2nao423.0479；found423.0468.
[0065]
5,10-difluoro-2,2-dimethyl-4a-phenyl-1,2,4,4a-tetrahydro-3h-pyrimido[1,2-a]quinolin-3-one(3o)
[0066]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＝13.2hz,1h),3.16(d,j＝13.2hz,1h),1.39(s,3h),1.23(s,3h).
13
c{1h}nmr(100mhz,cdcl3):δ175.5,155.4(d,j
c-f
＝272.1hz),152.8(d,j
c-f
＝240.5hz),141.1(d,j
c-f
＝3.5hz),129.2,128.8,128.3(d,j
c-f
＝8.1hz),125.5,124.7(dd,j
c-f
＝7.0hz,3.1hz),122.8(dd,j
c-f
＝5.5hz,2.7hz),122.3(d,j
c-f
＝8.2hz),116.3(d,j
c-f
＝20.0hz),103.2(dd,j
c-f
＝17.0hz,3.9hz),75.1(d,j
c-f
＝23.0hz),55.1(d,j
c-f
＝10.1hz),40.0,23.7,23.5.
19
fnmr(565mhz,cdcl3):δ-118.2(d,j＝13.6hz),-124.5(d,j＝13.6hz).hrms(esi)m/z:[m na]

calcdforc
20h18
f2n2nao363.1279；found363.1270.
[0067]
5-fluoro-2,2-dimethyl-4a-phenyl-1,2,4,4a-tetrahydro-3h-benzo[g]pyrimido[1,2-a]quinolin-3-one(3p)
[0068]1hnmr(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).
13
c{1h}nmr(150mhz,cdcl3):δ176.1,155.4(d,j
c-f
＝263.4hz),140.6(d,j
c-f
＝2.1hz),138.0,134.7,129.2,128.8,127.9,127.3,126.8(d,j
c-f
＝7.7hz),126.7,126.2,125.5,123.5,120.1(d,j
c-f
＝8.1hz),105.2,104.5(d,j
c-f
＝17.4hz),75.0(d,j
c-f
＝26.4hz),49.1,40.7,26.2,22.6.
19
fnmr(565mhz,cdcl3):δ-126.3(d,j＝11.9hz).hrms(esi)m/z:[m na]

calcdforc
24h21
fn2nao395.1530；found395.1519.
[0069]
5-fluoro-2,2-dimethyl-4a-(p-tolyl)-1,2,4,4a-tetrahydro-3h-pyrimido[1,2-a]quinolin-3-one(3q)
[0070]1hnmr(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).
13
c{1h}nmr(150mhz,cdcl3):δ176.0,153.0(d,j
c-f
＝257.7hz),139.5,139.1,138.6,129.4,129.1(d,j
c-f
＝2.1hz),127.9(d,j
c-f
＝7.1hz),125.7,118.3,117.0(d,j
c-f
＝7.7hz),109.9,104.1(d,j
c-f
＝16.1hz),75.5(d,j
c-f
＝27.3hz),48.7,40.8,26.1,22.6,21.1.
19
fnmr(565mhz,cdcl3):δ-128.7(d,j＝12.4hz).hrms(esi)m/z:[m na]

calcdforc
21h21
fn2nao359.1530；found359.1518.
[0071]
4a-(4-(tert-butyl)phenyl)-5-fluoro-2,2-dimethyl-1,2,4,4a-tetrahydro-3h-pyrimido[1,2-a]quinolin-3-one(3r)
[0072]1hnmr(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).
13
c{1h}nmr(100mhz,cdcl3):δ176.0,153.1(d,j
c-f
＝259.5hz),152.1,139.5,138.4(d,j
c-f
＝2.2hz),129.0(d,j
c-f
＝1.9hz),127.8(d,j
c-f
＝5.5hz),125.6,125.4,118.3,117.1(d,j
c-f
＝6.8hz),109.9,104.1(d,j
c-f
＝16.3hz),75.5(d,j
c-f
＝26.2hz),48.8(d,j
c-f
＝1.3hz),40.8,34.6,31.3,26.0,22.6.
19
fnmr(376mhz,cdcl3):δ-128.4(d,j＝10.5hz).hrms(esi)m/z:[m na]

calcdforc
24h27
fn2nao401.2000；found401.1991.
[0073]
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)
[0074]1hnmr(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).
13
c{1h}nmr(100mhz,cdcl3):δ176.1,152.9(d,j
c-f
＝259.4hz),142.0,140.4(d,j
c-f
＝1.3hz),140.1,139.4,129.2(d,j
c-f
＝2.3hz),128.9,128.0(d,j
c-f
＝6.5hz),127.7,127.4,127.2,126.2,118.5,116.9(d,j
c-f
＝7.5hz),110.0,104.3(d,j
c-f
＝15.6hz),75.5(d,j
c-f
＝26.9hz),48.9,40.9,26.1,22.6.
19
fnmr(565mhz,cdcl3):δ-128.6(d,j＝11.9hz).hrms(esi)m/z:[m na]

calcdforc
26h23
fn2nao421.1687；found421.1671.
[0075]
5-fluoro-4a-(4-fluorophenyl)-2,2-dimethyl-1,2,4,4a-tetrahydro-3h-pyrimido[1,2-a]quinolin-3-one(3t)
[0076]1hnmr(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＝14.0hz,2.0hz,1h),2.94(d,j＝14.4hz,1h),1.27(s,3h),1.19(s,3h).
13
c{1h}nmr(100mhz,cdcl3):δ176.0,163.0(d,j
c-f
＝246.7hz),152.7(d,j
c-f
＝259.3hz),139.3,137.5(d,j
c-f
＝3.0hz),129.2(d,j
c-f
＝2.8hz),128.0(d,j
c-f
＝5.8hz),127.7(d,j
c-f
＝8.5hz),118.6,116.8(d,j
c-f
＝7.5hz),115.6(d,j
c-f
＝21.7hz),110.0,104.3(d,j
c-f
＝16.1hz),75.2(d,j
c-f
＝26.9hz),48.8(d,j
c-f
＝1.4hz),40.8,26.0,22.6.
19
fnmr(376mhz,cdcl3):δ-112.7
–-112.8(m),-128.7(d,j＝10.5hz).hrms(esi)m/z:[m h]

calcdforc
20h19
f2n2o341.1460；found341.1458.
[0077]
4a-(4-chlorophenyl)-5-fluoro-2,2-dimethyl-1,2,4,4a-tetrahydro-3h-pyrimido[1,2-a]quinolin-3-one(3u)
[0078]1hnmr(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).
13
c{1h}nmr(150mhz,cdcl3):δ176.1,152.6(d,j
c-f
＝259.7hz),140.2(d,j
c-f
＝2.0hz),139.3,135.1,129.3(d,j
c-f
＝2.6hz),128.9,128.0(d,j
c-f
＝5.6hz),127.3,118.7,116.8(d,j
c-f
＝7.1hz),110.0,104.4(d,j
c-f
＝15.5hz),75.2(d,j
c-f
＝26.6hz),48.9,40.8,26.0,22.6.
19
fnmr(565mhz,cdcl3):δ-128.4(d,j＝13.0hz).hrms(esi)m/z:[m
na]

calcdforc
20h18
clfn2nao379.0984；found379.0965.
[0079]
4a-(4-bromophenyl)-5-fluoro-2,2-dimethyl-1,2,4,4a-tetrahydro-3h-pyrimido[1,2-a]quinolin-3-one(3v)
[0080]1hnmr(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).
13
c{1h}nmr(100mhz,cdcl3):δ176.1,152.5(d,j
c-f
＝259.6hz),140.8(d,j
c-f
＝1.2hz),139.3,131.9,129.3(d,j
c-f
＝2.1hz),128.0(d,j
c-f
＝5.9hz),127.6,123.4,118.7,116.8(d,j
c-f
＝7.9hz),110.0,104.5(d,j
c-f
＝16.0hz),75.3(d,j
c-f
＝26.8hz),48.9(d,j
c-f
＝1.9hz),40.8,26.0,22.6.
19
fnmr(376mhz,cdcl3):δ-128.4(d,j＝12.8hz).hrms(esi)m/z:[m na]

calcdforc
20h18
brfn2nao423.0479；found423.0467.
[0081]
4-(5-fluoro-2,2-dimethyl-3-oxo-1,2,3,4-tetrahydro-4ah-pyrimido[1,2-a]quinolin-4a-yl)benzonitrile(3w)
[0082]1hnmr(600mhz,cdcl3):δ7.83(s,1h),7.63(d,j＝8.4hz,2h),7.59(d,j＝9.0hz,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).
13
c{1h}nmr(150mhz,cdcl3):δ176.3,152.1(d,j
c-f
＝260.3hz),146.7(d,j
c-f
＝2.6hz),139.2,132.6,129.5(d,j
c-f
＝2.6hz),128.2(d,j
c-f
＝6.2hz),126.7,119.0,118.2,116.6(d,j
c-f
＝7.7hz),113.0,110.2,104.8(d,j
c-f
＝14.7hz),75.3(d,j
c-f
＝27.2hz),49.2,40.8,25.8,22.6.
19
fnmr(565mhz,cdcl3):δ-127.9(d,j＝13.0hz).hrms(esi)m/z:[m h]

calcdforc
21h19
fn3o348.1507；found348.1500.
[0083]
5-fluoro-2,2-dimethyl-4a-(4-(trifluoromethyl)phenyl)-1,2,4,4a-tetrahydro-3h-pyrimido[1,2-a]quinolin-3-one(3x)
[0084]1hnmr(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).
13
c{1h}nmr(100mhz,cdcl3):δ176.3,152.4(d,j
c-f
＝261.0hz),145.6,139.3,131.2(q,j
c-f
＝31.8hz),129.4(d,j
c-f
＝2.0hz),128.1(d,j
c-f
＝5.9hz),126.3,125.7(q,j
c-f
＝3.7hz),123.8(q,j
c-f
＝270.7hz),118.8,116.7(d,j
c-f
＝7.3hz),110.1,104.6(d,j
c-f
＝16.1hz),75.3(d,j
c-f
＝26.9hz),49.1,40.8,25.9,22.6.
19
fnmr(565mhz,cdcl3):δ-62.6(s),-127.8(d,j＝11.9hz).hrms(esi)m/z:[m h]

calcdforc
21h19
f4n2o391.1428；found391.1429.
[0085]
methyl4-(5-fluoro-2,2-dimethyl-3-oxo-1,2,3,4-tetrahydro-4ah-pyrimido[1,2-a]quinolin-4a-yl)benzoate(3y)
[0086]1hnmr(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).
13
c{1h}nmr(150mhz,cdcl3):δ176.0,166.4,152.4(d,j
c-f
＝259.4hz),146.2(d,j
c-f
＝1.8hz),139.3,130.9,130.0,129.3(d,j
c-f
＝2.0hz),128.1(d,j
c-f
＝5.9hz),125.9,118.7,116.7(d,j
c-f
＝7.1hz),110.0,104.7(d,j
c-f
＝14.9hz),75.5
(d,j
c-f
＝27.3hz),52.3,49.0,40.8,26.0,22.6. 19
fnmr(376mhz,cdcl3):δ-128.2(d,j＝10.9hz).hrms(esi)m/z:[m h]
calcd for c
22h22
fn2o3381.1609；found381.1611.
[0087]
5-fluoro-2,2-dimethyl-4a-(4-nitrophenyl)-1,2,4,4a-tetrahydro-3h-pyrimido[1,2-a] quinolin-3-one(3z)
[0088]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).
13
c{1h}nmr(100mhz,cdcl3):δ176.3,152.0(d,j
c-f
＝261.3hz), 148.4(d,j
c-f
＝1.8hz),148.2,139.1,129.5(d,j
c-f
＝2.1hz),128.2(d,j
c-f
＝6.2hz), 127.0,123.9,119.1,116.6(d,j
c-f
＝7.1hz),110.3,104.9(d,j
c-f
＝15.5hz),75.2(d, j
c-f
＝26.9hz),49.3,40.8,25.8,22.6.
19
fnmr(565mhz,cdcl3):δ-128.3(d,j＝ 11.9hz).hrms(esi)m/z:[m na]

calcd for c
20h18
fn3nao3390.1224；found 390.1221.
[0089]
5-fluoro-2,2-dimethyl-4a-(m-tolyl)-1,2,4,4a-tetrahydro-3h-pyrimido[1,2-a]quino lin-3-one(3aa)
[0090]1h nmr(400mhz,cdcl3):δ7.25-7.21(m,3h),7.15-7.12(m,2h),7.03(d,j＝6.8 hz,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).
13
c{1h}nmr(100 mhz,cdcl3):δ176.0,152.8(d,j
c-f
＝258.7hz),141.6(d,j
c-f
＝1.7hz),139.5, 138.5,129.8,129.1(d,j
c-f
＝1.9hz),128.6,127.9(d,j
c-f
＝6.3hz),126.4,123.0, 118.3,116.8(d,j
c-f
＝7.2hz),109.8,104.2(d,j
c-f
＝15.5hz),75.6(d,j
c-f
＝26.6 hz),48.8,40.9,26.1,22.6,21.6.
19
fnmr(565mhz,cdcl3):δ-128.4(d,j＝12.4 hz).hrms(esi)m/z:[m h]

calcd for c
21h22
fn2o337.1711；found337.1710.
[0091]
5-fluoro-4a-(3-methoxyphenyl)-2,2-dimethyl-1,2,4,4a-tetrahydro-3h-pyrimido[1, 2-a]quinolin-3-one(3bb)
[0092]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).
13
c{1h}nmr(150mhz,cdcl3):δ176.0,159.9, 152.8(d,j
c-f
＝259.2hz),143.2,139.4,129.7,129.1(d,j
c-f
＝1.8hz),127.9(d,j
c-f
＝6.2hz),118.4,118.1,116.9(d,j
c-f
＝7.5hz),114.0,112.0,109.9,104.3(d,j
c-f
＝ 15.5hz),75.5(d,j
c-f
＝27.6hz),55.3,48.9,40.8,26.0,22.7.
19
f nmr(565mhz, cdcl3):δ-128.5(d,j＝11.9hz).hrms(esi)m/z:[m na]

calcd for c
21h21
fn
2 nao2375.1479；found375.1473.
[0093]
5-fluoro-4a-(3-fluorophenyl)-2,2-dimethyl-1,2,4,4a-tetrahydro-3h-pyrimido[1,2
‑ꢀ
a]quinolin-3-one(3cc)
[0094]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).
13
c{1h} nmr(150mhz,cdcl3):δ176.1,163.0(d,j
c-f
＝246.9hz),152.5(d,j
c-f
＝258.3 hz),144.4(d,j
c-f
＝5.0hz),139.3,130.2(d,j
c-f
＝8.0hz),129.3(d,j
c-f
＝2.7hz), 128.0(d,j
c-f
＝7.4hz),
121.5(d,j
c-f
＝1.7hz),118.7,116.7(d,j
c-f
＝8.1hz),116.1 (d,j
c-f
＝22.2hz),113.2(d,j
c-f
＝21.2hz),110.0,104.5(d,j
c-f
＝16.4hz),75.2(d, j
c-f
＝27.3hz),49.0,40.8,25.9,22.6.
19
f nmr(565mhz,cdcl3):δ-111.5
–‑
111.6 (m),-128.4(d,j＝11.3hz).hrms(esi)m/z:[m h]

calcd for c
21h19
f2n2o 341.1460；found341.1459.
[0095]
4a-(3-chlorophenyl)-5-fluoro-2,2-dimethyl-1,2,4,4a-tetrahydro-3h-pyrimido[1,2
‑ꢀ
a]quinolin-3-one(3dd)
[0096]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).
13
c{1h}nmr(100 mhz,cdcl3):δ176.2,152.3(d,j
c-f
＝260.0hz),144.0(d,j
c-f
＝1.7hz),139.3, 135.0,130.0,129.3(d,j
c-f
＝2.1hz),129.2,128.1(d,j
c-f
＝6.1hz),126.1,124.1, 118.7,116.7(d,j
c-f
＝7.4hz),110.0,104.5(d,j
c-f
＝15.7hz),75.2(d,j
c-f
＝26.8 hz),49.0,40.8,25.9,22.6.
19
fnmr(565mhz,cdcl3):δ-127.9(d,j＝11.9hz). hrms(esi)m/z:[m na]

calcd for c
20h18
clfn2nao379.0984；found379.0972.
[0097]
4a-(3-bromophenyl)-5-fluoro-2,2-dimethyl-1,2,4,4a-tetrahydro-3h-pyrimido[1,2
‑ꢀ
a]quinolin-3-one(3ee)
[0098]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).
13
c{1h}nmr(150mhz,cdcl3):δ 176.1,152.3(d,j
c-f
＝259.1hz),144.2(d,j
c-f
＝2.0hz),139.3,132.2,130.2,129.3 (d,j
c-f
＝2.9hz),129.0,128.1(d,j
c-f
＝7.4hz),124.6,123.1,118.7,116.6(d,j
c-f
＝ 7.4hz),110.1,104.6(d,j
c-f
＝15.0hz),75.2(d,j
c-f
＝27.2hz),49.0,40.9,26.0, 22.7.
19
fnmr(565mhz,cdcl3):δ-128.1(d,j＝12.4hz).hrms(esi)m/z: [m na]

calcd for c
20h18
brfn2nao 423.0479；found423.0476.
[0099]
5-fluoro-2,2-dimethyl-4a-(3-nitrophenyl)-1,2,4,4a-tetrahydro-3h-pyrimido[1,2-a] quinolin-3-one(3ff)
[0100]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).
13
c{1h}nmr(100mhz, cdcl3):δ176.4,152.0(d,j
c-f
＝260.3hz),148.5,144.3(d,j
c-f
＝1.5hz),139.2, 131.8,129.9,129.5(d,j
c-f
＝2.7hz),128.2(d,j
c-f
＝5.6hz),124.0,120.9,119.1, 116.6(d,j
c-f
＝7.2hz),110.4,104.9(d,j
c-f
＝15.5hz),75.1(d,j
c-f
＝26.7hz),49.2, 40.8,25.8,22.5.
19
fnmr(565mhz,cdcl3):δ-127.7(d,j＝11.9hz).hrms(esi) m/z:[m na]

calcd for c
20h18
fn3nao3390.1224；found390.1218.
[0101]
4a-(3,5-dimethoxyphenyl)-5-fluoro-2,2-dimethyl-1,2,4,4a-tetrahydro-3h-pyrimid o[1,2-a]quinolin-3-one(3gg)
[0102]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).
13
c{1h}nmr(150mhz,cdcl3):δ176.1, 161.1,152.8(d,j
c-f
＝259.8hz),144.1(d,j
c-f
＝2.4hz),139.4,129.1(d,j
c-f
＝2.3 hz),127.9(d,j
c-f
＝7.1hz),118.4,116.9(d,j
c-f
＝7.8hz),110.0,104.4,104.2(d, j
c-f
＝15.6hz),100.3,75.5(d,j
c-f
＝26.3hz),55.4,49.0,40.8,26.0,22.7.
19
f nmr (376mhz,cdcl3):δ-128.8(d,j＝10.9hz).hrms(esi)m/z:[m h]

calcd for c
22h24
fn2o
3 383.1765；found383.1762.
[0103]
5-fluoro-4a-(2-fluorophenyl)-2,2-dimethyl-1,2,4,4a-tetrahydro-3h-pyrimido[1,2
‑ꢀ
a]quinolin-3-one(3hh)`
[0104]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).
13
c{1h}nmr(150mhz,cdcl3):δ175.7,160.1(d,j
c-f
＝248.3hz), 151.2(d,j
c-f
＝259.8hz),139.5,131.2(d,j
c-f
＝9.0hz),129.1(d,j
c-f
＝2.1hz), 128.2(dd,j
c-f
＝10.1hz,2.3hz),128.01,127.99(d,j
c-f
＝5.7hz),124.2(d,j
c-f
＝3.2hz),118.5,117.4(d,j
c-f
＝23.0hz),117.0(d,j
c-f
＝7.5hz),109.7,104.3(d,j
c-f
＝15.9hz),74.4(d,j
c-f
＝27.2hz),49.5,41.0,25.7,22.4.
19
f nmr(565mhz, cdcl3):δ-111.56
–‑
111.62(m),-129.1(t,j＝12.4hz).hrms(esi)m/z:[m h]
calcd for c
20h19
f2n2o 341.1460；found 341.1460.
[0105]
5-fluoro-2,2-dimethyl-4a-(naphthalen-2-yl)-1,2,4,4a-tetrahydro-3h-pyrimido[1,2
ꢀ‑
a]quinolin-3-one(3ii)
[0106]1h nmr(400mhz,cdcl3):δ7.88-7.79(m,4h),7.53-7.47(m,3h),7.16(t,j＝8.4 hz,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).
13
c{1h}nmr(150mhz,cdcl3):δ176.2,152.5(d,j
c-f
＝259.8 hz),139.5,138.8(d,j
c-f
＝2.0hz),133.4,132.5,129.3(d,j
c-f
＝1.7hz),129.2, 128.7,128.1(d,j
c-f
＝5.4hz),127.6,127.0,126.8,124.9,123.4,118.4,116.8(d,j
c-f
＝6.9hz),109.9,104.6(d,j
c-f
＝15.8hz),75.8(d,j
c-f
＝27.3hz),48.8,41.0,26.1, 22.6.
19
f nmr(565mhz,cdcl3):δ-128.6(d,j＝10.2hz).hrms(esi)m/z: [m h]

calcd for c
24h22
fn2o 373.1711；found 373.1717.
[0107]
5-fluoro-2,2-dimethyl-4a-(thiophen-3-yl)-1,2,4,4a-tetrahydro-3h-pyrimido[1,2-a] quinolin-3-one(3jj)
[0108]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).
13
c{1h}nmr(100mhz, cdcl3):δ175.8,153.3(d,j
c-f
＝261.1hz),142.8(d,j
c-f
＝1.8hz),139.3,129.0(d, j
c-f
＝2.6hz),127.7(d,j
c-f
＝5.6hz),127.3,125.4,123.1,118.8,117.7(d,j
c-f
＝8.2 hz),110.4,103.7(d,j
c-f
＝15.9hz),73.5(d,j
c-f
＝26.1hz),49.1,40.5,26.0,22.6. 19
f nmr(565mhz,cdcl3):δ-128.3
(d,j＝13.0hz).hrms(esi)m/z:[m na]
calcd for c
18h17
fn2naos 351.0938；found 351.0930.
[0109]
实施例4
[0110]
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：
[0111][0112]
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).
13
c{1h}nmr(150mhz,cdcl3):δ 155.1(d,j
c-f
＝259.4hz),149.2(d,j
c-f
＝13.5hz),145.3(d,j
c-f
＝2.3hz),135.8(d, j
c-f
＝4.7hz),129.7(d,j
c-f
＝5.9hz),129.4(d,j
c-f
＝6.0hz),128.8(d,j
c-f
＝3.2 hz),128.6,128.3(d,j
c-f
＝5.9hz),127.4,126.8(d,j
c-f
＝4.5hz),119.7(d,j
c-f
＝ 20.3hz).
19
f nmr(565mhz,cdcl3):δ-124.4(d,j＝10.7hz).hrms(esi)m/z: [m h]

calcd for c
15h11
fn 224.0870；found 224.0866.
[0113]
实施例5
[0114]
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：
[0115][0116]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。
[0117]
代表性产物表征数据如下： 3-fluoro-6-methyl-2-phenylquinoline(4b)：1h nmr(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).
13
c{1h} nmr(100mhz,cdcl3):δ155.3(d,j
c-f
＝259.5hz),148.1(d,j
c-f
＝14.3hz), 143.9(d,j
c-f
＝2.9hz),137.4,135.9(d,j
c-f
＝5.4hz),131.1(d,j
c-f
＝2.5hz),129.4, 129.3(d,j
c-f
＝3.7hz),129.2,128.5,128.4(d,j
c-f
＝4.6hz),125.6(d,j
c-f
＝4.7hz), 119.1(d,j
c-f
＝19.4hz),21.7.
19
f nmr(376mhz,cdcl3):δ-124.8(d,j＝10.9 hz).hrms(esi)m/z:[m h]

calcd for c
16h13
fn 238.1027；found 238.1029.
[0118]
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).
13
c{1h}nmr(150mhz,cdcl3):δ155.5(d,j
c-f
＝261.2hz),149.5(d, j
c-f
＝14.3hz),143.8(d,j
c-f
＝2.9hz),135.3(d,j
c-f
＝4.8hz),132.4(d,j
c-f
＝1.8 hz),131.3,129.9,129.4(d,j
c-f
＝5.9hz),129.3(d,j
c-f
＝5.7hz),128.8(d,j
c-f
＝ 3.9hz),128.6,121.5,118.8(d,j
c-f
＝21.0hz).
19
f nmr(565mhz,cdcl3):δ
ꢀ‑
122.6(d,j＝9.0hz).hrms(esi)m/z:[m h]

calcd for c
15h10
brfn 301.9975； found 301.9969.
[0119]
3-fluoro-2-(p-tolyl)quinoline(4d)：1h nmr(600mhz,cdcl3):δ8.08(d,j＝8.4 hz,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).
13
c{1h}nmr(150mhz,cdcl3):δ155.1(d,j
c-f
＝259.1hz),149.2(d, j
c-f
＝14.4hz),145.3(d,j
c-f
＝3.0hz),139.8,133.0(d,j
c-f
＝3.8hz),129.6,129.3, 129.2(d,j
c-f
＝5.6hz),128.7(d,j
c-f
＝2.1hz),128.2(d,j
c-f
＝5.7hz),127.2,126.8 (d,j
c-f
＝3.9hz),119.6(d,j
c-f
＝20.4hz),21.5.
19
f nmr(565mhz,cdcl3):δ
ꢀ‑
124.2(d,j＝10.7hz).hrms(esi)m/z:[m h]

calcd for c
16h13
fn 238.1027； found 238.1032.
[0120]
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). 13
c{1h}nmr(100mhz,cdcl3):δ155.0(d,j
c-f
＝258.9hz),147.7(d,j
c-f
＝13.4 hz),145.2(d,j
c-f
＝3.0hz),134.6(d,j
c-f
＝5.1hz),131.8,130.9(d,j
c-f
＝5.8hz), 129.6,129.0(d,j
c-f
＝2.0hz),128.4(d,j
c-f
＝5.2hz),127.6,126.8(d,j
c-f
＝4.8hz), 124.3,119.9(d,j
c-f
＝19.9hz).
19
f nmr(565mhz,cdcl3):δ-124.3(d,j＝11.3 hz).hrms(esi)m/z:[m h]

calcd for c
15h10
brfn 301.9975；found301.9979.
[0121]
2-([1,1'-biphenyl]-4-yl)-3-fluoroquinoline(4f)：1h nmr(600mhz,cdcl3):δ 8.19-8.17(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).
13
c{1h}nmr(100mhz,cdcl3):δ155.2(d,j
c-f
＝258.9hz), 148.7(d,j
c-f
＝14.7hz),145.3(d,j
c-f
＝2.9hz),142.4,140.6,134.7(d,j
c-f
＝4.9 hz),129.8(d,j
c-f
＝5.4hz),129.7,128.9,128.8(d,j
c-f
＝2.0hz),128.3(d,j
c-f
＝ 4.6hz),127.7,127.4,127.30,127.26,126.8(d,j
c-f
＝5.7hz),119.7(d,j
c-f
＝18.6 hz).
19
fnmr(565mhz,cdcl3):δ-124.2(d,j＝9.0hz).hrms(esi)m/z: [m h]

calcd for c
21h15
fn 300.1183；found300.1178.
[0122]
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,j
c-f
＝260.7hz),148.4,146.1 (d,j
c-f
＝14.7hz),145.3(d,j
c-f
＝2.1hz),141.7(d,j
c-f
＝5.6hz),130.3(d,j
c-f
＝ 4.7hz),129.9,129.4(d,j
c-f
＝1.5hz),128.8(d,j
c-f
＝5.4hz),128.3,126.9(d,j
c-f
＝5.1hz),123.7,120.4(d,j
c-f
＝19.7hz).
19
f nmr(565mhz,cdcl3):δ-124.4(d, j＝11.3hz).hrms(esi)m/z:[m h]

calcd for c
15h10
fn2o2269.0721；found 269.0724.
[0123]
methyl4-(3-fluoroquinolin-2-yl)benzoate(4h)：1h nmr(600mhz,cdcl3):δ 8.20-8.16(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).
13
c{1h}nmr(150mhz,cdcl3):δ 166.9,155.1(d,j
c-f
＝258.2hz),147.8(d,j
c-f
＝14.3hz),145.3(d,j
c-f
＝3.0hz), 139.9(d,j
c-f
＝6.2hz),130.9,129.8,129.7,129.3(d,j
c-f
＝5.3hz),129.0(d,j
c-f
＝ 3.3hz),128.6(d,j
c-f
＝5.4hz),127.8,126.9(d,j
c-f
＝3.8hz),120.0(d,j
c-f
＝19.7 hz),52.3.
19
f nmr(565mhz,cdcl3):δ-124.3(d,j＝13.0hz).hrms(esi)m/z: [m h]

calcd for c
17h13
fno2282.0925；found282.0924.
[0124]
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。