CN114716374B - 一种3号位取代的二氢喹啉衍生物及其制备方法 - Google Patents
一种3号位取代的二氢喹啉衍生物及其制备方法 Download PDFInfo
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- 125000005044 dihydroquinolinyl group Chemical class N1(CC=CC2=CC=CC=C12)* 0.000 title claims abstract description 15
- 238000002360 preparation method Methods 0.000 title abstract description 22
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims abstract description 52
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 46
- 239000001257 hydrogen Substances 0.000 claims abstract description 46
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 36
- 150000001875 compounds Chemical class 0.000 claims abstract description 34
- -1 3-substituted dihydroquinoline Chemical class 0.000 claims abstract description 27
- 229940126062 Compound A Drugs 0.000 claims abstract description 27
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 claims abstract description 27
- 239000000126 substance Substances 0.000 claims abstract description 13
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 10
- 238000000034 method Methods 0.000 claims abstract description 9
- 239000002994 raw material Substances 0.000 claims abstract description 8
- 239000013067 intermediate product Substances 0.000 claims abstract description 6
- 238000003756 stirring Methods 0.000 claims abstract description 6
- 239000003960 organic solvent Substances 0.000 claims abstract description 5
- 239000003054 catalyst Substances 0.000 claims abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 60
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 54
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 40
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical group [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 34
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 34
- 239000003480 eluent Substances 0.000 claims description 31
- 239000003208 petroleum Substances 0.000 claims description 20
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 20
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 10
- 238000006243 chemical reaction Methods 0.000 claims description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 3
- 230000035484 reaction time Effects 0.000 claims description 3
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 2
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 2
- CVICEEPAFUYBJG-UHFFFAOYSA-N 5-chloro-2,2-difluoro-1,3-benzodioxole Chemical group C1=C(Cl)C=C2OC(F)(F)OC2=C1 CVICEEPAFUYBJG-UHFFFAOYSA-N 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 125000000217 alkyl group Chemical group 0.000 abstract description 6
- 239000000758 substrate Substances 0.000 abstract description 4
- 125000003545 alkoxy group Chemical group 0.000 abstract description 2
- 150000005840 aryl radicals Chemical class 0.000 abstract description 2
- 229910052736 halogen Inorganic materials 0.000 abstract description 2
- 150000002367 halogens Chemical class 0.000 abstract description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 abstract description 2
- 238000002390 rotary evaporation Methods 0.000 description 30
- 150000007529 inorganic bases Chemical class 0.000 description 19
- 239000000047 product Substances 0.000 description 17
- AFQARFNXLJBLFN-UHFFFAOYSA-N n-[2-(chloromethyl)phenyl]-4-methylbenzenesulfonamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC1=CC=CC=C1CCl AFQARFNXLJBLFN-UHFFFAOYSA-N 0.000 description 16
- LIGACIXOYTUXAW-UHFFFAOYSA-N phenacyl bromide Chemical group BrCC(=O)C1=CC=CC=C1 LIGACIXOYTUXAW-UHFFFAOYSA-N 0.000 description 16
- 239000002904 solvent Substances 0.000 description 15
- 239000007787 solid Substances 0.000 description 14
- 238000000926 separation method Methods 0.000 description 10
- 238000010898 silica gel chromatography Methods 0.000 description 9
- 238000004440 column chromatography Methods 0.000 description 7
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 4
- VQFAIAKCILWQPZ-UHFFFAOYSA-N bromoacetone Chemical group CC(=O)CBr VQFAIAKCILWQPZ-UHFFFAOYSA-N 0.000 description 4
- 150000003248 quinolines Chemical group 0.000 description 4
- 229940027991 antiseptic and disinfectant quinoline derivative Drugs 0.000 description 3
- 238000010189 synthetic method Methods 0.000 description 3
- IRFSXVIRXMYULF-UHFFFAOYSA-N 1,2-dihydroquinoline Chemical compound C1=CC=C2C=CCNC2=C1 IRFSXVIRXMYULF-UHFFFAOYSA-N 0.000 description 2
- NIXWFSXJIYEJFQ-UHFFFAOYSA-N 2-(4-fluorophenyl)acetyl bromide Chemical group FC1=CC=C(CC(Br)=O)C=C1 NIXWFSXJIYEJFQ-UHFFFAOYSA-N 0.000 description 2
- YOSSZEQCUXKUFP-UHFFFAOYSA-N 2-(4-methylphenyl)acetyl bromide Chemical group CC1=CC=C(CC(Br)=O)C=C1 YOSSZEQCUXKUFP-UHFFFAOYSA-N 0.000 description 2
- ZFFBIQMNKOJDJE-UHFFFAOYSA-N 2-bromo-1,2-diphenylethanone Chemical group C=1C=CC=CC=1C(Br)C(=O)C1=CC=CC=C1 ZFFBIQMNKOJDJE-UHFFFAOYSA-N 0.000 description 2
- VUDTYIUNUSPULX-UHFFFAOYSA-N 2-bromopentan-3-one Chemical group CCC(=O)C(C)Br VUDTYIUNUSPULX-UHFFFAOYSA-N 0.000 description 2
- FJZITZZWUZCICE-UHFFFAOYSA-N N-[2-(chloromethyl)-4-methoxyphenyl]-4-methylbenzenesulfonamide Chemical compound ClCC1=CC(OC)=CC=C1NS(=O)(=O)C1=CC=C(C)C=C1 FJZITZZWUZCICE-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 229960001701 chloroform Drugs 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000011259 mixed solution Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical group [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 102000010400 1-phosphatidylinositol-3-kinase activity proteins Human genes 0.000 description 1
- DJLVGBSKZILPKN-UHFFFAOYSA-N C1(=CC=CC=C1)C=1CN(C2=CC=CC=C2C=1)S(=O)(=O)C1=CC=C(C)C=C1 Chemical compound C1(=CC=CC=C1)C=1CN(C2=CC=CC=C2C=1)S(=O)(=O)C1=CC=C(C)C=C1 DJLVGBSKZILPKN-UHFFFAOYSA-N 0.000 description 1
- YNONOHMNXNNLRH-UHFFFAOYSA-N C1C(C)=CC2=CC=CC=C2N1S(=O)(=O)C1=CC=C(C)C=C1 Chemical compound C1C(C)=CC2=CC=CC=C2N1S(=O)(=O)C1=CC=C(C)C=C1 YNONOHMNXNNLRH-UHFFFAOYSA-N 0.000 description 1
- JNNZPQSRNCBJRC-UHFFFAOYSA-N CC(C=C1)=CC=C1S(NC1=C(CCl)C=CC(C(F)(F)F)=C1)(=O)=O Chemical compound CC(C=C1)=CC=C1S(NC1=C(CCl)C=CC(C(F)(F)F)=C1)(=O)=O JNNZPQSRNCBJRC-UHFFFAOYSA-N 0.000 description 1
- MLPVCINONCTESG-UHFFFAOYSA-N CC(C=C1)=CC=C1S(NC1=C(CCl)C=CC(Cl)=C1)(=O)=O Chemical compound CC(C=C1)=CC=C1S(NC1=C(CCl)C=CC(Cl)=C1)(=O)=O MLPVCINONCTESG-UHFFFAOYSA-N 0.000 description 1
- YXSNNYARHBJTJR-UHFFFAOYSA-N CC(C=C1)=CC=C1S(NC1=C(CCl)C=CC(F)=C1)(=O)=O Chemical compound CC(C=C1)=CC=C1S(NC1=C(CCl)C=CC(F)=C1)(=O)=O YXSNNYARHBJTJR-UHFFFAOYSA-N 0.000 description 1
- PMSNNWSEGBXMDD-UHFFFAOYSA-N ClCC1=C(C(=CC=C1)C)NS(=O)(=O)C1=CC=C(C=C1)C Chemical compound ClCC1=C(C(=CC=C1)C)NS(=O)(=O)C1=CC=C(C=C1)C PMSNNWSEGBXMDD-UHFFFAOYSA-N 0.000 description 1
- INQDYEGMSFWQIG-UHFFFAOYSA-N ClCC1=C(C=C(C=C1)C)NS(=O)(=O)C1=CC=C(C=C1)C Chemical compound ClCC1=C(C=C(C=C1)C)NS(=O)(=O)C1=CC=C(C=C1)C INQDYEGMSFWQIG-UHFFFAOYSA-N 0.000 description 1
- GDPUGKSVXIYZGR-UHFFFAOYSA-N ClCC1=C(C=CC(=C1)C)NS(=O)(=O)C1=CC=C(C=C1)C Chemical compound ClCC1=C(C=CC(=C1)C)NS(=O)(=O)C1=CC=C(C=C1)C GDPUGKSVXIYZGR-UHFFFAOYSA-N 0.000 description 1
- 229940122880 Estrogen receptor agonist Drugs 0.000 description 1
- 238000007126 N-alkylation reaction Methods 0.000 description 1
- 108010055723 PDGF receptor tyrosine kinase Proteins 0.000 description 1
- 108091007960 PI3Ks Proteins 0.000 description 1
- 102000001742 Tumor Suppressor Proteins Human genes 0.000 description 1
- 108010040002 Tumor Suppressor Proteins Proteins 0.000 description 1
- 238000007239 Wittig reaction Methods 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229940125388 beta agonist Drugs 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- JOGKUKXHTYWRGZ-UHFFFAOYSA-N dactolisib Chemical compound O=C1N(C)C2=CN=C3C=CC(C=4C=C5C=CC=CC5=NC=4)=CC3=C2N1C1=CC=C(C(C)(C)C#N)C=C1 JOGKUKXHTYWRGZ-UHFFFAOYSA-N 0.000 description 1
- 229950006418 dactolisib Drugs 0.000 description 1
- 239000000262 estrogen Substances 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
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- 239000013076 target substance Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/58—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems with hetero atoms directly attached to the ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明公开一种3号位取代的二氢喹啉衍生物及其制备方法,其特征在于,包括以下步骤:S1.以化合物A及三苯基膦为原料在有机溶剂中进行反应,得到中间产物;S2.以化合物B及中间产物为原料,以碱性物质为催化剂,冰浴条件下搅拌反应,即得3号位取代的二氢喹啉衍生物;其中,化合物A的结构如式I所示,化合物B的结构如式II所示,3号位取代的二氢喹啉的结构式III所示:其中,R1选自氢、卤素、烷基、烷氧基或三氟甲基,R2选自烷基或芳基,R3选自氢或烷基,该方法拓宽了3号位取代的二氢喹啉类化合物合成的底物适用范围。
Description
技术领域
本发明涉及有机化合物技术领域,具体涉及一种3号位取代的二氢喹啉衍生物及其制备方法。
背景技术
二氢喹啉或者喹啉骨架及其衍生物经常出现在天然产物分子,药物分子中,例如,一系列的喹啉或者二氢喹啉衍生物都表现出各种各样的生理活性,但是目前的合成方法大部分都集中在2号位或者4号位取代的喹啉衍生物,而3号位取代的喹啉衍生物的合成报道相对较少,但是3号位取代的喹啉衍生物是众多药物分子中的核心骨架,例如,PDGF-RTKinhibitors是一种肿瘤抑制剂;Dactolisib是一种已进入临床的治疗具有PI3K靶点的抗癌药物;Estrongen receptorβagonist是一种β雌激素受体激动剂,在3号位取代的喹啉衍生物的合成报道中反应条件大多涉及金属催化或者反应条件比较严格,3号位取代二氢喹啉类化合物合成的底物范围较窄。
发明内容
本发明的目的在于,提供一种3号位取代的二氢喹啉衍生物及其制备方法,拓宽了3号位取代二氢喹啉类化合物合成的底物适用范围。
为达到上述技术目的,本申请采用以下技术方案:
第一方面,本申请提供一种3号位取代的二氢喹啉衍生物的制备方法,包括以下步骤:
S1.以化合物A及三苯基膦为原料在有机溶剂中进行反应,得到中间产物;
S2.以化合物B及中间产物为原料,以碱性物质为催化剂,冰浴条件下搅拌反应,即得3号位取代的二氢喹啉衍生物;
化合物A的结构如式I所示,化合物B的结构如式II所示,3号位取代的二氢喹啉的结构式III所示:
其中,R1选自氢、卤素、烷基、烷氧基或三氟甲基,R2选自烷基或芳基,R3选自氢或烷基。
优选地,化合物A、化合物B、三苯基膦以及碱性物质的摩尔比为1-1.2:1:1-1.2:2-2.5。
优选地,化合物A、化合物B、三苯基膦以及碱性物质的摩尔比为1.2:1:1.2:2.5。
优选地,碱性物质为无机碱。
优选地,无机碱为碳酸铯或碳酸铯。
优选地,步骤S1中,有机溶剂为二氯甲烷和/或三氯甲烷。
优选地,步骤S2中,搅拌反应的温度为0-10℃,反应时间为4-10h。
优选地,还包括利用洗脱剂分离纯化3号位取代的二氢喹啉衍生物。
优选地,洗脱剂石油醚和乙酸乙酯的混合液,其中,石油醚和乙酸乙酯的体积比为50-10:1。
第二方面,本申请提供一种3号位取代的二氢喹啉衍生物。
本发明的有益效果是:本申请以特定结构的化合物A和化合物B为原料,在三苯基膦和碱性条件下发生环化反应,制备了含二氢喹啉结构片段的化合物;通过该合成方法简单,可高效获得3号位取代二氢喹啉衍生物,并在较大程度上拓宽了3号位取代二氢喹啉类化合物合成的底物适用范围;且本工艺原料易得、反应条件温和、反应时间短、操作简便,产物收率较高,适于产业化。
具体实施方式
下面将结合本发明实施例,对本发明实施例中的技术方案进行清楚、完整地描述,基于本发明中的实施例,本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例,均属于本发明保护的范围。
本申请的实施例提供一种3号位取代的二氢喹啉衍生物的制备方法,包括以下步骤:将化合物A和三苯基膦加入二氯甲烷和/或三氯甲烷中,再加入化合物B和碱性物质后于0-10℃冰浴下搅拌反应4-10h,其中,待反应结束后采用柱层析进行分离,以体积比为50-10:1的石油醚和乙酸乙酯的混合溶液为洗脱剂洗脱目标物质得到洗脱液,将洗脱液蒸干即得3号位取代的二氢喹啉衍生物;化合物A的结构如式I所示,化合物B的结构如式II所示,制得的3号位取代的二氢喹啉衍生物的结构如式III所示:
该方法中,化合物A首先与三苯基膦反应生成Wittig试剂前体,然后在碱性条件下与α-溴代酮发生N烷基化反应,最后发生分子内的Wittig反应得到产物。
在一些实施例中,碱性物质为无机碱,在另一些实施例中,无机碱为碳酸铯或碳酸铯。
在一些实施例中,化合物A、化合物B、三苯基膦以及碱性物质的摩尔比为1-1.2:1:1-1.2:2-2.5。
本申请的实施例还提供一种3号位取代的二氢喹啉衍生物。
实施例1
本实施例中,化合物A为N-(2-(氯甲基)苯基)-4-甲基苯磺酰胺(R1为氢),化合物B为α-溴代苯乙酮(R2为苯基,R3为氢),无机碱为碳酸铯。
制备过程为:向干燥的圆底烧瓶中加入N-(2-(氯甲基)苯基)-4-甲基苯磺酰胺(178mg,0.6mmol)并用5ml二氯甲烷溶解,然后加入三苯基膦(157mg,0.6mmol),最后加入α-溴代苯乙酮(100mg,0.5mmol),碳酸铯(408mg,1.25mmol),4℃冰浴搅拌6小时后旋蒸浓缩,硅胶柱柱层析(洗脱剂为石油醚与乙酸乙酯体积比25:1的混合液)分离收集洗脱液,旋蒸除溶剂得到3-苯基-1-甲苯磺酰基-1,2-二氢喹啉166mg,白色固体,产率92%。
对所得产物进行验证,数据如下:
1H NMR(400MHz,CDCl3)δ7.77(d,J=8.0Hz,1H),7.40–7.34(m,2H),7.34–7.25(m,4H),7.24–7.19(td,J=7.5,1.2Hz,1H),7.16(d,J=8.3Hz,2H),7.03(dd,J=7.5,1.4Hz,1H),6.91(d,J=8.0Hz,2H),6.30(s,1H),4.80(s,2H),2.28(s,3H).13C NMR(100MHz,CDCl3)δ143.4,137.4,135.6,134.5,134.2,130.5,128.9,128.7,128.3,127.9,127.1,127.0,127.0,126.8,125.1,121.3,47.6,21.5。
实施例2
本实施例中,化合物A为N-(2-(氯甲基)-5-三氟甲基-苯基)-4-甲基苯磺酰胺(R1为5-三氟甲基),化合物B为α-溴代苯乙酮(R2为苯基,R3为氢),无机碱为碳酸铯。
制备过程为:向干燥的圆底烧瓶中加入N-(2-(氯甲基)-5-三氟甲基-苯基)-4-甲基苯磺酰胺(218mg,0.6mmol)并用5ml二氯甲烷溶解,然后加入三苯基膦(157mg,0.6mmol),最后加入α-溴代苯乙酮(100mg,0.5mmol),碳酸铯(408mg,1.25mmol),0℃冰浴搅拌4小时后旋蒸浓缩,硅胶柱柱层析(洗脱剂为石油醚与乙酸乙酯体积比25:1的混合液)分离收集洗脱液,旋蒸除溶剂得到3-苯基-1-甲苯磺酰基-7-三氟甲基-1,2-二氢喹啉143mg,白色固体,产率67%。
对所得产物进行验证,数据如下:
M.p.133-135℃。1H NMR(400MHz,CDCl3)δ8.03(s,1H),7.45(d,J=8.0Hz,1H),7.39(q,J=7.6,6.5Hz,3H),7.31–7.27(m,2H),7.19(d,J=8.3Hz,2H),7.13(d,J=7.9Hz,1H),6.94(d,J=8.2Hz,2H),6.37(s,1H),4.84(s,2H),2.29(s,3H).13C NMR(100MHz,CDCl3)δ143.9,137.3,136.7,135.4,134.6,133.3,129.6(q,JC-F=326.8Hz),129.1,128.9,128.8,127.2,127.1,125.3,123.8(q,JC-F=3.9Hz),123.5(q,JC-F=3.8Hz),120.1,47.4,21.5。
实施例3
本实施例中,化合物A为N-(2-(氯甲基)-4-甲氧基-苯基)-4-甲基苯磺酰胺(R1为4-甲氧基),化合物B为α-溴代苯乙酮(R2为苯基,R3为氢),无机碱为碳酸铯。
制备过程为:向干燥的圆底烧瓶中加入N-(2-(氯甲基)-4-甲氧基-苯基)-4-甲基苯磺酰胺(196mg,0.6mmol)并用5ml二氯甲烷溶解,然后加入三苯基膦(157mg,0.6mmol),最后加入α-溴代苯乙酮(100mg,0.5mmol),碳酸铯(408mg,1.25mmol),10℃冰浴搅拌10小时后旋蒸浓缩,硅胶柱柱层析(洗脱剂为石油醚与乙酸乙酯体积比25:1的混合液)分离收集洗脱液,旋蒸除溶剂得到6-甲氧基-3-苯基-1-甲苯磺酰基-1,2-二氢喹啉150mg,白色固体,产率77%。
对所得产物进行验证,数据如下:
M.p.137-139℃。1H NMR(400MHz,CDCl3)δ7.68(d,J=8.8Hz,1H),7.34(m,3H),7.24(d,J=7.0Hz,2H),7.14(d,J=8.2Hz,2H),6.92(d,J=8.0Hz,2H),6.85(dd,J=8.8,2.8Hz,1H),6.55(d,J=2.7Hz,1H),6.23(s,1H),4.76(s,2H),3.82(s,3H),2.29(s,3H).13C NMR(100MHz,CDCl3)δ158.4,143.3,137.4,135.5,135.1,131.6,128.8,128.7,128.3,128.1,127.2,127.2,125.2,121.3,113.1,111.8,55.5,47.8,21.5。
实施例4
本实施例中,化合物A为N-(2-(氯甲基)-5-氟-苯基)-4-甲基苯磺酰胺(R1为5-氟),化合物B为α-溴代苯乙酮(R2为苯基,R3为氢),无机碱为碳酸铯。
制备过程为:向干燥的圆底烧瓶中加入N-(2-(氯甲基)-5-氟-苯基)-4-甲基苯磺酰胺(188mg,0.6mmol)并用5ml二氯甲烷溶解,然后加入三苯基膦(157mg,0.6mmol),最后加入α-溴代苯乙酮(100mg,0.5mmol),碳酸铯(408mg,1.25mmol),4℃冰浴搅拌6小时后旋蒸浓缩,硅胶柱柱层析(洗脱剂为石油醚与乙酸乙酯体积比25:1的混合液)分离收集洗脱液,旋蒸除溶剂得到7-氟-3-苯基-1-甲苯磺酰基-1,2-二氢喹啉70mg,白色固体,产率37%。
对所得产物进行验证,数据如下:
M.p.153-155℃。1H NMR(400MHz,CDCl3)δ7.54(dd,J=9.9,2.5Hz,1H),7.40–7.30(m,3H),7.28–7.24(m,2H),7.22(d,J=8.3Hz,2H),7.02–6.97(m,1H),6.97–6.90(m,3H),6.30(s,1H),4.80(s,2H),2.29(s,3H).13C NMR(100MHz,CDCl3)δ161.6(d,JC-F=246.0Hz),143.7,137.2,135.7(d,JC-F=10.9Hz),135.6,133.5(d,JC-F=2.6Hz),129.0,128.7,128.3,128.0,127.9,127.1,126.7(d,JC-F=3.3Hz),125.1,120.4,114.1(d,JC-F=11.5Hz),113.9(d,JC-F=8.2Hz),47.34,21.49。
实施例5
本实施例中,化合物A为N-(2-(氯甲基)-5-氯-苯基)-4-甲基苯磺酰胺(R1为5-氯),化合物B为α-溴代苯乙酮(R2为苯基,R3为氢),无机碱为碳酸铯。
制备过程为:向干燥的圆底烧瓶中加入N-(2-(氯甲基)-5-氯-苯基)-4-甲基苯磺酰胺(200mg,0.6mmol)并用5ml二氯甲烷溶解,然后加入三苯基膦(157mg,0.6mmol),最后加入α-溴代苯乙酮(100mg,0.5mmol),碳酸铯(408mg,1.25mmol),4℃冰浴搅拌6小时后旋蒸浓缩,硅胶柱柱层析(洗脱剂为石油醚与乙酸乙酯体积比25:1的混合液)分离收集洗脱液,旋蒸除溶剂得到7-氯-3-苯基-1-甲苯磺酰基-1,2-二氢喹啉67mg,白色固体,产率34%。
对所得产物进行验证,数据如下:
M.p.163-165℃。1H NMR(400MHz,CDCl3)δ7.79(d,J=2.0Hz,1H),7.40–7.32(m,3H),7.28–7.24(m,2H),7.23–7.17(m,3H),6.98–6.93(m,3H),6.29(s,1H),4.79(d,J=1.2Hz,2H),2.30(s,3H).13C NMR(100MHz,CDCl3)δ143.7,137.1,135.5,135.3,134.8,133.0,129.0,128.9,128.7,128.5,127.7,127.1,127.1,126.7,125.1,120.3,47.4,21.5。
实施例6
本实施例中,化合物A为N-(2-(氯甲基)-4-甲基-苯基)-4-甲基苯磺酰胺(R1为4-甲基),化合物B为α-溴代苯乙酮(R2为苯基,R3为氢),无机碱为碳酸铯。
制备过程为:向干燥的圆底烧瓶中加入N-(2-(氯甲基)-4-甲基-苯基)-4-甲基苯磺酰胺(186mg,0.6mmol)并用5ml二氯甲烷溶解,然后加入三苯基膦(157mg,0.6mmol),最后加入α-溴代苯乙酮(100mg,0.5mmol),碳酸铯(408mg,1.25mmol),4℃冰浴搅拌6小时后旋蒸浓缩,硅胶柱柱层析(洗脱剂为石油醚与乙酸乙酯体积比25:1的混合液)分离收集洗脱液,旋蒸除溶剂得到6-甲基-3-苯基-1-甲苯磺酰基-1,2-二氢喹啉139mg,白色固体,产率74%。
对所得产物进行验证,数据如下:
M.p.135-137℃。1H NMR(400MHz,CDCl3)δ7.64(d,J=8.1Hz,1H),7.38–7.33(m,2H),7.33–7.28(m,1H),7.24(m,2H),7.16(d,J=8.3Hz,2H),7.10(dd,J=8.2,1.5Hz,1H),6.91(d,J=8.0Hz,2H),6.84(d,J=1.5Hz,1H),6.25(s,1H),4.76(s,2H),2.34(s,3H),2.28(s,3H).13C NMR(100MHz,CDCl3)δ143.2,137.5,136.7,135.7,134.4,131.7,130.2,128.8,128.7,128.7,128.1,127.5,127.1,126.6,125.1,121.4,47.7,21.5,21.1。
实施例7
本实施例中,化合物A为N-(2-(氯甲基)-5-甲基-苯基)-4-甲基苯磺酰胺(R1为5-甲基),化合物B为α-溴代苯乙酮(R2为苯基,R3为氢),无机碱为碳酸铯。
制备过程为:向干燥的圆底烧瓶中加入N-(2-(氯甲基)-5-甲基-苯基)-4-甲基苯磺酰胺(186mg,0.6mmol)并用5ml二氯甲烷溶解,然后加入三苯基膦(157mg,0.6mmol),最后加入α-溴代苯乙酮(100mg,0.5mmol),碳酸铯(408mg,1.25mmol),4℃冰浴搅拌6小时后旋蒸浓缩,硅胶柱柱层析(洗脱剂为石油醚与乙酸乙酯体积比25:1的混合液)分离收集洗脱液,旋蒸除溶剂得到7-甲基-3-苯基-1-甲苯磺酰基-1,2-二氢喹啉123mg,白色固体,产率66%。
对所得产物进行验证,数据如下:
M.p.144-146℃。1H NMR(400MHz,CDCl3)δ7.60(s,1H),7.39–7.29(m,3H),7.26–7.22(m,2H),7.16(d,J=8.3Hz,2H),7.04(d,J=7.7Hz,1H),6.92(m,3H),6.28(s,1H),4.77(s,2H),2.43(s,3H),2.28(s,3H).13C NMR(100MHz,CDCl3)δ143.3,138.2,137.6,135.7,134.2,133.3,128.8,128.6,128.0,127.8,127.8,127.3,127.1,126.7,125.1,121.2,47.6,21.6,21.5。
实施例8
本实施例中,化合物A为N-(2-(氯甲基)-6-甲基-苯基)-4-甲基苯磺酰胺(R1为6-甲基),化合物B为α-溴代苯乙酮(R2为苯基,R3为氢),无机碱为碳酸铯。
制备过程为:向干燥的圆底烧瓶中加入N-(2-(氯甲基)-6-甲基-苯基)-4-甲基苯磺酰胺(186mg,0.6mmol)并用5ml二氯甲烷溶解,然后加入三苯基膦(157mg,0.6mmol),最后加入α-溴代苯乙酮(100mg,0.5mmol),碳酸铯(408mg,1.25mmol),4℃冰浴搅拌6小时后旋蒸浓缩,硅胶柱柱层析(洗脱剂为石油醚与乙酸乙酯体积比25:1的混合液)分离收集洗脱液,旋蒸除溶剂得到8-甲基-3-苯基-1-甲苯磺酰基-1,2-二氢喹啉174mg,白色固体,产率93%。
对所得产物进行验证,数据如下:
M.p.136-138℃。1H NMR(400MHz,CDCl3)δ7.35–7.25(m,3H),7.24–7.20(m,1H),7.18(d,J=7.4Hz,1H),7.14(d,J=8.2Hz,4H),6.90(d,J=8.0Hz,2H),6.84(d,J=7.3Hz,1H),6.17(d,J=2.44Hz,1H),5.12(d,J=17.6Hz,1H),4.23(dd,J=17.6,2.5Hz,1H),2.63(s,3H),2.29(s,3H).13C NMR(100MHz,CDCl3)δ143.3,137.7,137.3,135.7,135.1,133.1,131.9,130.9,128.7,128.5,128.1,127.7,127.4,124.8,124.6,122.1,48.4,21.5,19.5。
实施例9
本实施例中,化合物A为N-(2-(氯甲基)苯基)-4-甲基苯磺酰胺(R1为氢),化合物B为α-溴代(4-氟苯基)乙酮(R2为4-氟苯基,R3为氢),无机碱为碳酸钾。
制备过程为:向干燥的圆底烧瓶中加入N-(2-(氯甲基)苯基)-4-甲基苯磺酰胺(178mg,0.6mmol)并用5ml二氯甲烷溶解,然后加入三苯基膦(157mg,0.6mmol),最后加入α-溴代(4-氟苯基)乙酮(109mg,0.5mmol),碳酸铯(408mg,1.25mmol),4℃冰浴搅拌6小时后旋蒸浓缩,硅胶柱柱层析(洗脱剂为石油醚与乙酸乙酯体积比25:1的混合液)分离收集洗脱液,旋蒸除溶剂得到3-(4-氟苯基)-1-甲苯磺酰基-1,2-二氢喹啉108mg,白色固体,产率57%。
对所得产物进行验证,数据如下:
M.p.125-127℃。1H NMR(400MHz,CDCl3)δ7.76(d,J=8.0Hz,1H),7.31(td,J=7.8,1.5Hz,1H),7.26–7.20(m,3H),7.15(d,J=8.3Hz,2H),7.09–7.00(m,3H),6.93(d,J=8.1Hz,2H),6.25(s,1H),4.76(s,2H),2.29(s,3H).13C NMR(100MHz,CDCl3)δ162.6(d,JC-F=247.1Hz),143.4,135.6,134.2,133.6(d,JC-F=3.3Hz),133.4,130.3,128.7,128.0,127.0,126.9(d,JC-F=5.4Hz),126.8(d,JC-F=5.1Hz),126.8,121.1,115.8,115.6,47.5,21.5。
实施例10
本实施例中,化合物A为N-(2-(氯甲基)苯基)-4-甲基苯磺酰胺(R1为氢),化合物B为α-溴代(3-吡啶)乙酮(R2为3-吡啶,R3为氢),无机碱为碳酸铯。
制备过程为:向干燥的圆底烧瓶中加入N-(2-(氯甲基)苯基)-4-甲基苯磺酰胺(178mg,0.6mmol)并用5ml二氯甲烷溶解,然后加入三苯基膦(157mg,0.6mmol),最后加入α-溴代(3-吡啶)乙酮(101mg,0.5mmol),碳酸铯(408mg,1.25mmol),4℃冰浴搅拌6小时后旋蒸浓缩,硅胶柱柱层析(洗脱剂为石油醚与乙酸乙酯体积比25:1的混合液)分离收集洗脱液,旋蒸除溶剂得到3-(3-吡啶)-1-甲苯磺酰基-1,2-二氢喹啉119mg,白色固体,产率66%。
对所得产物进行验证,数据如下:
M.p.208-209℃。1H NMR(400MHz,CDCl3)δ8.55(d,J=4.1Hz,1H),8.47(s,1H),7.78(d,J=8.0Hz,1H),7.60–7.53(m,1H),7.38–7.29(m,2H),7.26(td,J=7.5,1.2Hz,1H),7.15(d,J=8.3Hz,2H),7.07(dd,J=7.5,1.5Hz,1H),6.95(d,J=8.0Hz,2H),6.37(s,1H),4.78(d,J=1.2Hz,2H),2.30(s,3H).13C NMR(100MHz,CDCl3)δ149.1,146.6,143.7,135.6,134.4,133.1,132.2,131.2,129.8,129.0,128.6,127.3,127.1,127.0,127.0,123.4,122.8,47.1,21.5。
实施例11
本实施例中,化合物A为N-(2-(氯甲基)苯基)-4-甲基苯磺酰胺(R1为氢),化合物B为α-溴代(4-吡啶)乙酮(R2为4-吡啶,R3为氢),无机碱为碳酸铯。
制备过程为:向干燥的圆底烧瓶中加入N-(2-(氯甲基)苯基)-4-甲基苯磺酰胺(148mg,0.5mmol)并用5ml二氯甲烷溶解,然后加入三苯基膦(131mg,0.5mmol),最后加入α-溴代(4-吡啶)乙酮(101mg,0.5mmol),碳酸铯(326mg,1mmol),4℃冰浴搅拌6小时后旋蒸浓缩,硅胶柱柱层析(洗脱剂为石油醚与乙酸乙酯体积比25:1的混合液)分离收集洗脱液,旋蒸除溶剂得到3-(4-吡啶)-1-甲苯磺酰基-1,2-二氢喹啉96mg,白色固体,产率53%。
对所得产物进行验证,数据如下:
M.p.135-138℃。1H NMR(400MHz,CDCl3)δ8.61(d,J=5.0Hz,2H),7.79(d,J=8.0Hz,1H),7.37(td,J=7.8,1.5Hz,1H),7.29–7.24(m,1H),7.17–7.11(m,4H),7.09(dd,J=7.6,1.4Hz,1H),6.92(d,J=8.0Hz,2H),6.52(s,1H),4.78(s,2H),2.29(s,3H).13C NMR(100MHz,CDCl3)δ150.2,144.4,143.7,135.5,134.9,131.5,129.4,129.1,129.0,127.6,127.2,127.0,127.0,124.5,119.3,46.6,21.5。
实施例12
本实施例中,化合物A为N-(2-(氯甲基)苯基)-4-甲基苯磺酰胺(R1为氢),化合物B为2-溴-1,2-二苯基-乙酮(R2为苯基,R3为苯基),无机碱为碳酸铯。
制备过程为:向干燥的圆底烧瓶中加入N-(2-(氯甲基)苯基)-4-甲基苯磺酰胺(178mg,0.6mmol)并用5ml二氯甲烷溶解,然后加入三苯基膦(157mg,0.6mmol),最后加入2-溴-1,2-二苯基-乙酮(138mg,0.5mmol),碳酸铯(408mg,1.25mmol),4℃冰浴搅拌6小时后旋蒸浓缩,硅胶柱柱层析(洗脱剂为石油醚与乙酸乙酯体积比25:1的混合液)分离收集洗脱液,旋蒸除溶剂得到2,3-二苯基-1-甲苯磺酰基-1,2-二氢喹啉152mg,白色固体,产率70%。
对所得产物进行验证,数据如下:
M.p.140-142℃。1H NMR(400MHz,CDCl3)δ7.63(d,J=7.4Hz,1H),7.40–7.35(m,2H),7.32–7.26(m,3H),7.23–7.12(m,9H),7.06(dd,J=7.3,1.8Hz,1H),6.92(d,J=8.0Hz,2H),6.65(s,1H),6.43(s,1H),2.29(s,3H).13C NMR(100MHz,CDCl3)δ143.3,137.7,137.3,135.8,135.6,132.0,129.9,128.9,128.6,128.5,128.2,128.2,128.1,128.0,127.7,127.1,126.8,126.7,125.4,121.8,59.3,21.5。
实施例13
本实施例中,化合物A为N-(2-(氯甲基)苯基)-4-甲基苯磺酰胺(R1为氢),化合物B为α-溴代(4-甲基苯基)乙酮(R2为4-甲基苯基,R3为氢),无机碱为碳酸铯。
制备过程为:向干燥的圆底烧瓶中加入N-(2-(氯甲基)苯基)-4-甲基苯磺酰胺(178mg,0.6mmol)并用5ml二氯甲烷溶解,然后加入三苯基膦(157mg,0.6mmol),最后加入α-溴代(4-甲基苯基)乙酮(107mg,0.5mmol),碳酸铯(408mg,1.25mmol),4℃冰浴搅拌6小时后旋蒸浓缩,硅胶柱柱层析(洗脱剂为石油醚与乙酸乙酯体积比25:1的混合液)分离收集洗脱液,旋蒸除溶剂得到3-(4-甲基苯基)-1-甲苯磺酰基-1,2-二氢喹啉153mg,白色固体,产率85%。
对所得产物进行验证,数据如下:
M.p.141-143℃。1H NMR(400MHz,CDCl3)δ7.76(d,J=7.9Hz,1H),7.27(td,J=7.8,1.6Hz,1H),7.22–7.13(m,7H),7.00(dd,J=7.5,1.5Hz,1H),6.91(d,J=8.0Hz,2H),6.26(s,1H),4.77(d,J=1.3Hz,2H),2.37(s,3H),2.27(s,3H).13CNMR(100MHz,CDCl3)δ143.3,138.3,135.6,134.6,134.1,130.6,129.4,128.8,127.7,127.1,126.9,126.9,126.8,125.1,120.4,47.6,21.5,21.3。
实施例14
本实施例中,化合物A为N-(2-(氯甲基)苯基)-4-甲基苯磺酰胺(R1为氢),化合物B为1-溴-丙酮(R2为甲基,R3为氢),无机碱为碳酸铯。
制备过程为:向干燥的圆底烧瓶中加入N-(2-(氯甲基)苯基)-4-甲基苯磺酰胺(178mg,0.6mmol)并用5ml二氯甲烷溶解,然后加入三苯基膦(157mg,0.6mmol),最后加入1-溴-丙酮(68mg,0.5mmol),碳酸铯(408mg,1.25mmol),4℃冰浴搅拌6小时后旋蒸浓缩,硅胶柱柱层析(洗脱剂为石油醚与乙酸乙酯体积比25:1的混合液)分离收集洗脱液,旋蒸除溶剂得到3-甲基-1-甲苯磺酰基-1,2-二氢喹啉124mg,无色油状液体,产率83%。
对所得产物进行验证,数据如下:
1H NMR(400MHz,CDCl3)δ7.60(d,J=7.9Hz,1H),7.19–7.11(m,3H),7.07(td,J=7.4,1.3Hz,1H),6.99(d,J=8.0Hz,2H),6.78(dd,J=7.4,1.5Hz,1H),5.64(s,1H),4.17(s,2H),2.26(s,3H),1.57(s,3H).13C NMR(100MHz,CDCl3)δ143.4,136.0,133.8,133.6,130.6,129.0,126.9,126.8,126.8,126.8,125.7,120.9,49.4,21.5,20.7。
实施例15
本实施例中,化合物A为N-(2-(氯甲基)苯基)-4-甲基苯磺酰胺(R1为氢),化合物B为2-溴-3-戊酮(R2为乙基,R3为甲基),无机碱为碳酸铯。
制备过程为:向干燥的圆底烧瓶中加入N-(2-(氯甲基)苯基)-4-甲基苯磺酰胺(178mg,0.6mmol)并用5ml二氯甲烷溶解,然后加入三苯基膦(157mg,0.6mmol),最后加入2-溴-3-戊酮(82mg,0.5mmol),碳酸铯(408mg,1.25mmol),4℃冰浴搅拌6小时后旋蒸浓缩,硅胶柱柱层析(洗脱剂为石油醚与乙酸乙酯体积比25:1的混合液)分离收集洗脱液,旋蒸除溶剂得到3-乙基-2-甲基-1-甲苯磺酰基-1,2-二氢喹啉114mg,白色固体,产率70%。
对所得产物进行验证,数据如下:
M.p.95-97℃。1H NMR(400MHz,CDCl3)δ7.72(d,J=7.9Hz,1H),7.26–7.19(m,3H),7.16(td,J=7.5,1.3Hz,1H),7.04(d,J=8.0Hz,2H),6.92(dd,J=7.5,1.5Hz,1H),5.66(s,1H),4.66(q,J=6.9Hz,1H),2.32(s,3H),2.13–2.02(m,1H),1.91–1.80(m,1H),1.11(d,J=6.9Hz,3H),0.88(t,J=7.4Hz,3H).13C NMR(100MHz,CDCl3)δ144.2,143.2,136.0,131.6,129.6,128.8,127.7,127.0,126.9,126.5,125.7,117.1,54.4,26.9,21.5,18.6,11.1。
本发明中所使用的已知的起始原料可以提供本领域已知的方法来合成,或者通过常规的商业手段来购买。本发明的化合物的制备可以通过本领域技术人员所熟知的合成方法来实现,包括但不限于以上列举的具体实施方式、其与其他化学合成方法相结合而形成的实施方式以及本领域技术人员所熟知的等同替换方式,优选的实施方式包括但不限于本发明的实施例。
Claims (5)
1.一种3号位取代的二氢喹啉衍生物的制备方法,其特征在于,包括以下步骤:
S1.以化合物A及三苯基膦为原料在有机溶剂中进行反应,得到中间产物;
S2.以化合物B及所述中间产物为原料,以碱性物质为催化剂,冰浴条件下搅拌反应,即得所述3号位取代的二氢喹啉衍生物;
所述化合物A的结构如式I所示,所述化合物B的结构如式II所示,所述3号位取代的二氢喹啉的结构式III所示:
所述碱性物质为碳酸铯;步骤S2中,搅拌反应的温度为0-10℃,反应时间为4-10h;式III中的R1、R2、R3的代表基团包括以下组分方式中的一种:
R1为氢、R2为苯基、R3为氢;R1为5-三氟甲基、R2为苯基、R3为氢;R1为4-甲氧基、R2为苯基、R3为氢;R1为5-氟、R2为苯基、R3为氢;R1为5-氯、R2为苯基、R3为氢;R1为4-甲基、R2为苯基、R3为氢;R1为5-甲基、R2为苯基、R3为氢;R1为6-甲基、R2为苯基、R3为氢;R1为氢、R2为4-氟苯基、R3为氢;R1为氢、R2为3-吡啶、R3为氢;R1为氢、R2为4-吡啶、R3为氢;R1为氢、R2为苯基、R3为苯基;R1为氢、R2为4-甲基苯基、R3为氢;R1为氢、R2为甲基、R3为氢;R1为氢、R2为乙基、R3为甲基;式I中R1及式II中的R2、R3如所对应的式III中所述的R1、R2、R3,步骤S1中,所述有机溶剂为二氯甲烷和/或三氯甲烷。
2.根据权利要求1所述的3号位取代的二氢喹啉衍生物的制备方法,其特征在于,所述化合物A、化合物B、三苯基膦以及碱性物质的摩尔比为1-1.2:1:1-1.2:2-2.5。
3.根据权利要求2所述的3号位取代的二氢喹啉衍生物的制备方法,其特征在于,所述化合物A、化合物B、三苯基膦以及碱性物质的摩尔比为1.2:1:1.2:2.5。
4.根据权利要求1所述的3号位取代的二氢喹啉衍生物的制备方法,其特征在于,所述S2步骤之后还包括,利用洗脱剂分离纯化所述3号位取代的二氢喹啉衍生物。
5.根据权利要求4所述的3号位取代的二氢喹啉衍生物的制备方法,其特征在于,所述洗脱剂石油醚和乙酸乙酯的混合液,其中,所述石油醚和乙酸乙酯的体积比为50-10:1。
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