CN104557686A - 一种吡啶酮类化合物的合成方法 - Google Patents
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- -1 pyridinone compound Chemical class 0.000 title abstract description 5
- 238000001308 synthesis method Methods 0.000 title abstract 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 23
- 238000009833 condensation Methods 0.000 claims abstract description 3
- 230000005494 condensation Effects 0.000 claims abstract description 3
- 150000003222 pyridines Chemical class 0.000 claims description 15
- 238000010189 synthetic method Methods 0.000 claims description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 11
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 claims description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- 125000004185 ester group Chemical group 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 150000005826 halohydrocarbons Chemical class 0.000 claims description 4
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- 125000003118 aryl group Chemical group 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 239000000460 chlorine Substances 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- 239000011630 iodine Chemical group 0.000 claims description 2
- 229910052740 iodine Chemical group 0.000 claims description 2
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 2
- 230000015572 biosynthetic process Effects 0.000 abstract description 3
- 238000000034 method Methods 0.000 abstract description 3
- 238000003786 synthesis reaction Methods 0.000 abstract description 3
- 150000002894 organic compounds Chemical class 0.000 abstract description 2
- 239000002994 raw material Substances 0.000 abstract description 2
- 150000008282 halocarbons Chemical class 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 42
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- 238000004821 distillation Methods 0.000 description 7
- 239000012044 organic layer Substances 0.000 description 7
- RHWKPHLQXYSBKR-BMIGLBTASA-N dolutegravir Chemical compound C([C@@H]1OCC[C@H](N1C(=O)C1=C(O)C2=O)C)N1C=C2C(=O)NCC1=CC=C(F)C=C1F RHWKPHLQXYSBKR-BMIGLBTASA-N 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 229960002542 dolutegravir Drugs 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
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- 238000005406 washing Methods 0.000 description 3
- 229940099797 HIV integrase inhibitor Drugs 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 229950005928 cabotegravir Drugs 0.000 description 2
- WCWSTNLSLKSJPK-LKFCYVNXSA-N cabotegravir Chemical compound C([C@H]1OC[C@@H](N1C(=O)C1=C(O)C2=O)C)N1C=C2C(=O)NCC1=CC=C(F)C=C1F WCWSTNLSLKSJPK-LKFCYVNXSA-N 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000003084 hiv integrase inhibitor Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- FBZVZUSVGKOWHG-UHFFFAOYSA-N 1,1-dimethoxy-n,n-dimethylethanamine Chemical compound COC(C)(OC)N(C)C FBZVZUSVGKOWHG-UHFFFAOYSA-N 0.000 description 1
- QKWWDTYDYOFRJL-UHFFFAOYSA-N 2,2-dimethoxyethanamine Chemical compound COC(CN)OC QKWWDTYDYOFRJL-UHFFFAOYSA-N 0.000 description 1
- 0 CN**[*+]=C=C Chemical compound CN**[*+]=C=C 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 1
- 208000031886 HIV Infections Diseases 0.000 description 1
- HBBGRARXTFLTSG-UHFFFAOYSA-N Lithium ion Chemical compound [Li+] HBBGRARXTFLTSG-UHFFFAOYSA-N 0.000 description 1
- WRQNANDWMGAFTP-UHFFFAOYSA-N Methylacetoacetic acid Chemical compound COC(=O)CC(C)=O WRQNANDWMGAFTP-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 108020005202 Viral DNA Proteins 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
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- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
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- 229960003586 elvitegravir Drugs 0.000 description 1
- JUZYLCPPVHEVSV-LJQANCHMSA-N elvitegravir Chemical compound COC1=CC=2N([C@H](CO)C(C)C)C=C(C(O)=O)C(=O)C=2C=C1CC1=CC=CC(Cl)=C1F JUZYLCPPVHEVSV-LJQANCHMSA-N 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 229910001416 lithium ion Inorganic materials 0.000 description 1
- JILPJDVXYVTZDQ-UHFFFAOYSA-N lithium methoxide Chemical compound [Li+].[O-]C JILPJDVXYVTZDQ-UHFFFAOYSA-N 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- LVWZTYCIRDMTEY-UHFFFAOYSA-N metamizole Chemical compound O=C1C(N(CS(O)(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 LVWZTYCIRDMTEY-UHFFFAOYSA-N 0.000 description 1
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 150000005299 pyridinones Chemical class 0.000 description 1
- 229960004742 raltegravir Drugs 0.000 description 1
- CZFFBEXEKNGXKS-UHFFFAOYSA-N raltegravir Chemical compound O1C(C)=NN=C1C(=O)NC(C)(C)C1=NC(C(=O)NCC=2C=CC(F)=CC=2)=C(O)C(=O)N1C CZFFBEXEKNGXKS-UHFFFAOYSA-N 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229940014075 tivicay Drugs 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/79—Acids; Esters
- C07D213/803—Processes of preparation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/79—Acids; Esters
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/79—Acids; Esters
- C07D213/80—Acids; Esters in position 3
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pyridine Compounds (AREA)
Abstract
本发明涉及有机化合物合成领域，具体涉及一种吡啶酮类化合物的合成方法。一种吡啶酮类化合物的合成方法，包括如下步骤：（a）将原料和卤代烃在碱性条件下反应制得化合物中间体；（b）将步骤（a）所得化合物中间体与胺类化合物通过缩合即可得到所述吡啶酮类化合物。本发明中的工艺路线短，收率高，操作简单无危害性。
Description
技术领域
本发明涉及有机化合物合成领域，具体涉及一种吡啶酮类化合物的合成方法。
背景技术
Dolutegravir是由葛兰素史克(GlaxoSmithKline，GSK)公司旗下的ViiV Healthcare HIV专业公司开发的抗HIV-1感染药物，商品名为Tivicay，临床上使用的是其钠盐，剂型为50 mg薄膜包衣片，于2013年8月12日获美国FDA批准上市。以下分别是Dolutegravir和Cabotegravir的钠盐结构。
Dolutegravir是HIV整合酶抑制剂，它能阻止病毒DNA链向宿主DNA转移。与现有的HIV整合酶抑制剂雷特格韦(raltegravir)、埃替格韦(elvitegravir)相比，该药物的安全性提高。例如，WO2006116764对化合物结构进行了保护，WO2010011819保护了其前药形式，WO2010068262、WO2010068253、WO2012018065对Dolutegravir的制备工艺进行了保护。而中间体吡啶酮是合成Dolutegravir和Cabotegravir的关键。在WO2011119566A1中，以4-甲氧基乙酰乙酸乙酯为原料，和N,N-二甲基-1,1-二甲氧基乙胺反应得到3-(二甲氨基)-2[(甲氧基)乙酰基]-2-丙烯酸甲酯，再与1,1-二甲氧基乙胺合成化合物1，在（MOR，其中R为烷基，M为碱金属阳离子，优选锂离子）条件下与化合物2得到吡啶酮3（如下所示）。
但是该工艺过程较为复杂，步骤繁多，第三步需要用到甲醇锂等醇碱化合物，不易保存，价格较贵，反应时间较长，不利于工业化生产。
发明内容
本发明的目的是针对现有技术的不足，提供一种步骤简单、高效、环境友好、 经济适合工业化生产的吡啶酮类化合物的合成方法。
本发明所要解决的技术问题通过以下技术方案予以实现：
一种吡啶酮类化合物的合成方法，包括如下步骤：
（a）将化合物I和卤代烃R3X在碱性条件下反应制得化合物II；
（b）将步骤（a）所得化合物II与胺类化合物III通过缩合即可得到所述吡啶酮类化合物IV；
其中，X为氯、溴或者碘；R1为H、羧基或者低级烷基酯基；R2为低级烷基或者芳基；R3为低级烷基；R4为H或者低级烷基。
进一步的，所述R1为H、羧基或者低级烷基酯基；R2为甲基、乙基或者苄基；R3为甲基；R4为甲基或者乙基。
进一步的，所述R1为甲酯基；R2为甲基；R3为甲基；R4为甲基。
进一步的，所述化合物I和卤代烃R3X的摩尔比为1:1.2~1.5。
进一步的，所述化合物II与胺类化合物III的摩尔比为1:1.5~2。
步骤（a）中所用的碱性物质为本技术领域常用的碱均可实现本发明，如碳酸氢钠，碳酸氢钾等物质。
本发明具有如下有益效果：
本发明中的工艺路线短，收率高，操作简单无危害性。
具体实施方式
下面结合实施例对本发明进行详细的说明，实施例仅是本发明的优选实施方式，不是对本发明的限定。
下述实施例中所使用的实验方法如无特殊说明，均为常规方法。
下述实施例中所用的材料、试剂等，如无特殊说明，均可从商业途径得到。
实施例1
一种吡啶酮类化合物的合成方法，包括如下步骤：
（a）将214g化合物I溶于1L N-甲基吡咯烷酮中，加入168g NaHCO3和170g CH3I，40℃搅拌反应6h，再冷却，加入2M HCl溶液和20%氯化钠溶液，析出晶体，过滤，用水洗涤，干燥即得化合物 194g(收率为85%)。
（b）将114g化合物和105g2,2-二甲氧基乙胺混合，加入至650mL乙醇当中，搅拌升温至回流反应至结束，冷却，加入200mL水和400mL乙酸乙酯，分层后，水层用乙酸乙酯洗涤两次，合并有机层，硫酸镁干燥后，再减压蒸馏溶剂后得到目标产物 129g(收率82%)。 ESI-MS [M+H]+ 316.0，1H NMR (300 MHz, DMSO) δ 15.4 (s, 1 H)，8.22 (s, 1 H), 4.90-4.80 (m, 1 H), 3.88 (s, 3H), 3.78 (s, 3H), 3.74 (d, J = 5.0 Hz, 2H), 3.60 (s, 6H)。
实施例2
一种吡啶酮类化合物的合成方法，包括如下步骤：
（a）将246g化合物I溶于1L N-甲基吡咯烷酮中，加入168gNaHCO3和170gCH3I，40℃搅拌反应6h，再冷却，加入2M HCl溶液，用乙酸乙酯萃取后用饱和NaCl溶液洗涤有机层，减压蒸馏乙酸乙酯后得到化合物 197g(收率为76%)。
（b）将130g化合物和77g 2,2-二羟基乙胺混合，加入650mL乙醇，搅拌升温至回流反应至结束，冷却，加入200mL水和400mL乙酸乙酯，分层后，水层用乙酸乙酯洗涤两次，合并有机层，硫酸镁干燥后，再减压蒸馏溶剂后得到目标产物 115g(收率72%)。 ESI-MS [M+H]+ 320.1，1H NMR (300 MHz, DMSO) δ 7.62 (d, J = 7.5 Hz, 1 H), 7.42-7.30 (m, 5H), 6.33 (d, J = 6.0 Hz, 2H), 6.29 (d, J = 7.5 Hz, 1 H), 5.08 (s, 2H), 4.95-4.85 (m, 1 H), 3.80 (s, 3H), 3.74 (d, J = 5.1 Hz, 2H)。
实施例3
一种吡啶酮类化合物的合成方法，包括如下步骤：
（a）将170g化合物I溶于1L N-甲基吡咯烷酮中，加入168gNaHCO3和170g CH3I，40℃搅拌反应6h，再冷却，加入2M HCl溶液，用乙酸乙酯萃取后用饱和NaCl溶液洗涤有机层，减压蒸馏乙酸乙酯后得到化合物 151g(收率为82%)。
（b）将92g化合物和105g2,2-二甲氧基乙胺混合，加入500mL乙醇，搅拌升温至回流反应至结束，冷却，加入200mL水和400mL乙酸乙酯，分层后，水层用乙酸乙酯洗涤两次，合并有机层，硫酸镁干燥后，再减压蒸馏溶剂后得到目标产物 122g收率90%)。 ESI-MS [M+H]+ 272.1，1H NMR (300 MHz, DMSO) δ 7.66 (d, J = 7.3 Hz, 1 H), 6.21 (d, J = 7.3 Hz, 1 H), 4.90-4.82 (m, 1 H), 3.88 (s, 3H), 3.80 (s, 3H), 3.76 (d, J = 4.8 Hz, 2H), 3.59 (s, 6H)。
实施例4
一种吡啶酮类化合物的合成方法，包括如下步骤：
(a)将化合物I溶于1L N-甲基吡咯烷酮中，加入168gNaHCO3和170g CH3I，40℃搅拌反应6h，再冷却，加入2M HCl溶液，用乙酸乙酯萃取后用饱和NaCl溶液洗涤有机层，减压蒸馏乙酸乙酯后得到化合物 210g(收率为87%)。
(b)将121g化合物和105g 2,2-二甲氧基乙胺混合，加入500mL乙醇，搅拌升温至回流反应至结束，冷却，加入200mL水和400mL乙酸乙酯，分层后，水层用乙酸乙酯洗涤两次，合并有机层，硫酸镁干燥后，再减压蒸馏溶剂后得到目标产物 148g(收率90%)。 ESI-MS [M+H]+ 330.1，1H NMR (300 MHz, DMSO) δ 8.14 (s, 1 H), 4.90-4.80 (m, 1 H), 3.88 (s, 3H), 3.82 (s, 3H), 3.78 (s, 3H), 3.74 (d, J = 5.0 Hz, 2H), 3.60 (s, 6H)。
以上所述实施例仅表达了本发明的实施方式，其描述较为具体和详细，但并不能因此而理解为对本发明专利范围的限制，但凡采用等同替换或等效变换的形式所获得的技术方案，均应落在本发明的保护范围之内。
Claims (5)
1.一种吡啶酮类化合物的合成方法，其特征在于包括如下步骤：
（a）将化合物I和卤代烃R3X在碱性条件下反应制得化合物II；
（b）将步骤（a）所得化合物II与胺类化合物III通过缩合即可得到所述吡啶酮类化合物IV；
其中，X为氯、溴或者碘；R1为H、羧基或者低级烷基酯基；R2为低级烷基或者芳基；R3为低级烷基；R4为H或者低级烷基。
2.根据权利要求1所述的一种吡啶酮类化合物的合成方法，其特征在于，所述R1为H、羧基或者低级烷基酯基；R2为甲基、乙基或者苄基；R3为甲基；R4为甲基或者乙基。
3.根据权利要求2所述的一种吡啶酮类化合物的合成方法，其特征在于，所述R1为甲酯基；R2为甲基；R3为甲基；R4为甲基。
4.根据权利要求1所述的一种吡啶酮类化合物的合成方法，其特征在于，所述化合物I和卤代烃R3X的摩尔比为1:1.2~1.5。
5.根据权利要求1所述的一种吡啶酮类化合物的合成方法，其特征在于，所述化合物II与胺类化合物III的摩尔比为1:1.5~2。
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