CN115093410B - 一种β-咔啉类化合物的制备方法 - Google Patents
一种β-咔啉类化合物的制备方法 Download PDFInfo
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- CN115093410B CN115093410B CN202210787707.6A CN202210787707A CN115093410B CN 115093410 B CN115093410 B CN 115093410B CN 202210787707 A CN202210787707 A CN 202210787707A CN 115093410 B CN115093410 B CN 115093410B
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- tryptamine
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- -1 beta-carboline compound Chemical class 0.000 title claims abstract description 177
- AIFRHYZBTHREPW-UHFFFAOYSA-N cis-beta-Carboline Acid Natural products N1=CC=C2C3=CC=CC=C3NC2=C1 AIFRHYZBTHREPW-UHFFFAOYSA-N 0.000 title claims abstract description 68
- 238000002360 preparation method Methods 0.000 title claims abstract description 67
- 238000006243 chemical reaction Methods 0.000 claims abstract description 118
- APJYDQYYACXCRM-UHFFFAOYSA-N tryptamine Chemical compound C1=CC=C2C(CCN)=CNC2=C1 APJYDQYYACXCRM-UHFFFAOYSA-N 0.000 claims abstract description 72
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 57
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 57
- 239000001301 oxygen Substances 0.000 claims abstract description 57
- 150000001875 compounds Chemical class 0.000 claims abstract description 50
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 164
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 151
- 238000003756 stirring Methods 0.000 claims description 94
- 239000003960 organic solvent Substances 0.000 claims description 51
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims description 49
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 49
- 238000010898 silica gel chromatography Methods 0.000 claims description 48
- 238000001035 drying Methods 0.000 claims description 47
- 238000001914 filtration Methods 0.000 claims description 46
- 239000000203 mixture Substances 0.000 claims description 43
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- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzenecarboxaldehyde Natural products O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 claims description 9
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- 238000005303 weighing Methods 0.000 claims description 4
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical class CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 claims description 2
- WWTBZEKOSBFBEM-SPWPXUSOSA-N (2s)-2-[[2-benzyl-3-[hydroxy-[(1r)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C(CP(O)(=O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 WWTBZEKOSBFBEM-SPWPXUSOSA-N 0.000 claims description 2
- IWZSHWBGHQBIML-ZGGLMWTQSA-N (3S,8S,10R,13S,14S,17S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine Chemical compound CN(C)[C@H]1CC[C@]2(C)C3CC[C@@]4(C)[C@@H](CC[C@@H]4c4ccc5ccncc5c4)[C@@H]3CC=C2C1 IWZSHWBGHQBIML-ZGGLMWTQSA-N 0.000 claims description 2
- QYIXCDOBOSTCEI-QCYZZNICSA-N (5alpha)-cholestan-3beta-ol Chemical class C([C@@H]1CC2)[C@@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@H](C)CCCC(C)C)[C@@]2(C)CC1 QYIXCDOBOSTCEI-QCYZZNICSA-N 0.000 claims description 2
- OLZAGZCCJJBKNZ-UJPOAAIJSA-N 4-[(2s,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxybenzaldehyde Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=CC=C(C=O)C=C1 OLZAGZCCJJBKNZ-UJPOAAIJSA-N 0.000 claims description 2
- CNOPDZWOYFOHGN-BQYQJAHWSA-N Beta-Ionol Chemical class CC(O)\C=C\C1=C(C)CCCC1(C)C CNOPDZWOYFOHGN-BQYQJAHWSA-N 0.000 claims description 2
- LZCDAPDGXCYOEH-UHFFFAOYSA-N adapalene Chemical class C1=C(C(O)=O)C=CC2=CC(C3=CC=C(C(=C3)C34CC5CC(CC(C5)C3)C4)OC)=CC=C21 LZCDAPDGXCYOEH-UHFFFAOYSA-N 0.000 claims description 2
- 229940126208 compound 22 Drugs 0.000 claims description 2
- OLZAGZCCJJBKNZ-UHFFFAOYSA-N formaldehydephenlyl-O-beta-D-pyranosyl alloside Natural products OC1C(O)C(O)C(CO)OC1OC1=CC=C(C=O)C=C1 OLZAGZCCJJBKNZ-UHFFFAOYSA-N 0.000 claims description 2
- 150000002303 glucose derivatives Chemical class 0.000 claims description 2
- NBKQRVSGHYZUOR-UHFFFAOYSA-N indoline-3-carbaldehyde Natural products C1=CC=C2C(C=O)CNC2=C1 NBKQRVSGHYZUOR-UHFFFAOYSA-N 0.000 claims description 2
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 claims description 2
- 238000007792 addition Methods 0.000 claims 3
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- 150000002500 ions Chemical class 0.000 abstract description 6
- LWNGJAHMBMVCJR-UHFFFAOYSA-N (2,3,4,5,6-pentafluorophenoxy)boronic acid Chemical compound OB(O)OC1=C(F)C(F)=C(F)C(F)=C1F LWNGJAHMBMVCJR-UHFFFAOYSA-N 0.000 abstract description 4
- 229930014626 natural product Natural products 0.000 abstract description 4
- 238000001308 synthesis method Methods 0.000 abstract description 4
- OHSJPLSEQNCRLW-UHFFFAOYSA-N triphenylmethyl radical Chemical compound C1=CC=CC=C1[C](C=1C=CC=CC=1)C1=CC=CC=C1 OHSJPLSEQNCRLW-UHFFFAOYSA-N 0.000 abstract description 4
- 229910052755 nonmetal Inorganic materials 0.000 abstract description 3
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- 229940079593 drug Drugs 0.000 abstract 1
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 abstract 1
- 150000003839 salts Chemical class 0.000 abstract 1
- 238000005481 NMR spectroscopy Methods 0.000 description 92
- 239000007787 solid Substances 0.000 description 36
- 239000002904 solvent Substances 0.000 description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- 239000007800 oxidant agent Substances 0.000 description 7
- 230000001590 oxidative effect Effects 0.000 description 7
- 229910052739 hydrogen Inorganic materials 0.000 description 6
- 239000001257 hydrogen Substances 0.000 description 6
- NTYXKFHKVREUMR-UHFFFAOYSA-N 4,9-dihydro-3h-pyrido[3,4-b]indole Chemical compound N1C2=CC=CC=C2C2=C1C=NCC2 NTYXKFHKVREUMR-UHFFFAOYSA-N 0.000 description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 150000003934 aromatic aldehydes Chemical class 0.000 description 4
- 230000003197 catalytic effect Effects 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- BTFQKIATRPGRBS-UHFFFAOYSA-N o-tolualdehyde Chemical compound CC1=CC=CC=C1C=O BTFQKIATRPGRBS-UHFFFAOYSA-N 0.000 description 4
- CFTOTSJVQRFXOF-UHFFFAOYSA-N 2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole Chemical class N1C2=CC=CC=C2C2=C1CNCC2 CFTOTSJVQRFXOF-UHFFFAOYSA-N 0.000 description 3
- 239000001431 2-methylbenzaldehyde Substances 0.000 description 3
- JTEJPPKMYBDEMY-UHFFFAOYSA-N 5-methoxytryptamine Chemical compound COC1=CC=C2NC=C(CCN)C2=C1 JTEJPPKMYBDEMY-UHFFFAOYSA-N 0.000 description 3
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- IAVREABSGIHHMO-UHFFFAOYSA-N 3-hydroxybenzaldehyde Chemical compound OC1=CC=CC(C=O)=C1 IAVREABSGIHHMO-UHFFFAOYSA-N 0.000 description 2
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- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
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Abstract
本发明公开了一种β‑咔啉类化合物的制备方法，属于有机化学合成技术领域。该β‑咔啉类化合物是具有式Ⅲ所示的化合物。本发明在氧气氛围下，能够通过色胺和醛在离子对盐催化三苯碳四(五氟苯基)硼酸盐(Ph3C+[B(C6F5)4]‑)的条件下一步制得式Ⅲ所示的β‑咔啉类化合物。本发明提供β‑咔啉类化合物的新合成路线具有新颖、高效、原子经济性高、反应条件温和和底物适用范围广等优点，在天然产物活性物质或者小分子药物分子合成领域具有潜在的应用前景。本发明制备方法中所需的催化剂为非金属类型的催化剂，与现有的金属催化的合成方法相比，合成过程更易于纯化，不存在金属残留的问题。作为医药中间体，不存在金属残留导致的生物毒性。
Description
技术领域
本发明涉及有机化学合成技术领域，尤其涉及一种β-咔啉类化合物及其制备方法。
背景技术
β-咔啉是一种极其重要的化合物，存在于植物、海洋生物、细菌、真菌、食品等自然资源中，具有多种多样的生物活性，包括抗疟疾、抗肿瘤和抗艾滋病毒等。其中一些作为地西泮拮抗剂而受到关注，另一些则与中枢神经系统的苯二氮卓受体表现出强大的结合亲和力，从而发挥地西泮拮抗剂的作用。因此，开发温和而实用的芳香β-咔啉合成方法是化学家们关注的热点。
基于1,2,3,4-四氢化-β-咔啉构建芳香β-咔啉框架是比较主流的方法，因为四氢-β-咔啉易通过Pictet-Spengler反应制得。四氢-β-咔啉通过使用不同的条件和不同的试剂，将其进行芳构化。另外由于3,4-二氢-β-咔啉可以通过Bischler Napieralski环化反应得到，因此，3,4-二氢-β-咔啉的芳构化反应也是获得β-咔啉的一种方法。然而，无受体脱氢法采用贵金属作为催化剂，氧化法往往使用强氧化剂。有报道称以C或者S负载的Pd作为催化剂或者使用过量的氧化剂如SeO2、MnO2、KMnO4，在高沸点烃类溶剂中长时间高温处理。这些方法大多需要剧烈的条件。氯醌,DDQ,三氯异氰尿酸,PhI(OAc)2,NCS和IBX也被用于参与芳构化，但这些方法的缺点是：容易产生贵金属残留问题、需使用过量的试剂、产生大量的化学废物、反应效率低并且反应适用范围比较有限。
氧气是空气的重要组成部分，而空气是地球上最丰富的资源之一，因此氧气被认为是一种清洁和生态友好的氧化剂，具有安全、无毒、廉价、易得等优点。近几十年来，越来越多的研究人员利用氧气作为氧化剂进行各种氧化反应。然而，由于3,4-二氢-β-咔啉在大多数溶剂中溶解度低，利用空气作为氧化剂进行3,4-二氢-β-咔啉氧化转化为芳香β-咔啉仍然是一项非常具有挑战性的课题。
Wendlandt等人[22]还报道了一种模拟生物合成的路线，用于3,4-二氢-β-咔啉的合成，但此合成方法不能进一步得到芳香化的β-咔啉。
到目前为止，很少有关于一锅法无金属催化以色胺与醛为反应物直接形成β-咔啉的报道。
发明内容
本发明的目的在于提供一种β-咔啉类化合物的制备方法，在该制备方法中，原料简单易得，底物范围宽阔，反应条件温和，只使用少量的催化剂，成本低，反应效率高。本发明制备方法中所需的催化剂为非金属类型的催化剂，与现有的金属催化的合成方法相比，合成过程更易于纯化，不存在金属残留的问题。
为了解决本发明的技术问题，提出的技术方案为：一种β-咔啉类化合物的制备方法，，该方法包括以下步骤：
上式(Ⅲ)中，R1为氢、甲基、甲氧基、三氟甲基、三氟甲氧基、氟、氯、溴、碘、羟基中的任意一种；
R2为氢、甲基、羧基、甲氧酰基、乙氧酰基中的任意一种；
R3为苯基、对甲基苯基、邻甲基苯基、间甲基苯基、对甲氧基苯基、间甲氧基苯基、邻甲氧基苯基、对氟苯基、邻氟苯基、间氟苯基、对氯苯基、邻氯苯基、间氯苯基、对溴苯基、邻溴苯基、间溴苯基、对羟基苯基、间羟基苯基、邻羟基苯基、对乙基苯基、对异丙基苯基、对叔丁基苯基、3,4,5-三氟苯基、五氟苯基、4-二甲氨基苯基、4-丙酰氧基苯基、对三氟甲基苯基、间三氟甲基苯基、邻三氟甲基苯基、对三氟甲氧基苯基、间三氟甲氧基苯基、邻三氟甲氧基苯基、2,5-二氯苯基、对乙炔基苯基、对乙烯基苯基、对氰基苯基、对硝基苯基、4-联苯基、间苯氧基苯基、4-甲磺酰基苯基、4-羧基苯基、3，4-二甲基苯基、2-萘基、3-吲哚基、2-噻吩基、2-吡咯基、2-吡啶基、3-吡啶基、苯并咪唑、N-乙基-3-咔啉基中的任意一种；
具体制备步骤如下：
(1)在氧气氛围下，将色胺或色胺衍生物式(Ⅰ)、醛类衍生物式(Ⅱ)以及三苯碳四(五氟苯基)硼酸盐催化剂依次加入至反应器中，然后加入水或有机溶剂，得到混合物，其中，所述色胺或者色胺衍生物、芳香醛衍生物、三苯碳四(五氟苯基)硼酸盐(Ph3C+[B(C6F5)4]-)以及溶剂的摩尔体积比为：0.1mmol～10mmol：0.15mmol～15mmol：0.02mmol～2mmol：1mL～20mL；
(2)将步骤(1)中得到的混合物在加热条件下反应12～24小时，得到β-咔啉类化合物式(Ⅲ)。
优选的，在步骤(2)中所述加热温度为120℃，反应时间为12小时，步骤(1)中所述溶剂为甲苯，色胺或色胺衍生物、芳香醛衍生物、离子对催化剂以及溶剂的摩尔体积比为：0.2mmol:0.3mmol:0.04mmol:1mL。
优选的，在步骤(1)中所述色胺或色胺衍生物为色胺及盐酸盐、5-氯色胺及盐酸盐、5-溴色胺及盐酸盐、5-甲基色胺及盐酸盐、5-甲氧基色胺及盐酸盐、色胺酸、色胺酸甲酯及盐酸盐、色胺酸乙酯及盐酸盐中的任意一种。
优选的，在步骤(1)中所述醛衍生物为苯甲醛、对甲基苯甲醛、邻甲基苯甲醛、间甲基苯甲醛、对甲氧基苯甲醛、间甲氧基苯甲醛、邻甲氧基苯甲醛、对氟苯甲醛、邻氟苯甲醛、间氟苯甲醛、对氯苯甲醛、邻氯苯甲醛、间氯苯甲醛、对溴苯甲醛、邻溴苯甲醛、间溴苯甲醛、对羟基苯甲醛、间羟基苯甲醛、邻羟基苯甲醛、对乙基苯甲醛、对异丙基苯甲醛、对叔丁基苯甲醛、3,4,5-三氟苯甲醛、五氟苯甲醛、4-二甲氨基苯甲醛、4-丙酰氧基苯甲醛、对三氟甲基苯甲醛、间三氟甲基苯甲醛、邻三氟甲基苯甲醛、对三氟甲氧基苯甲醛、间三氟甲氧基苯甲醛、邻三氟甲氧基苯甲醛、2,5-二氯苯甲醛、对乙炔基苯甲醛、对乙烯基苯甲醛、对氰基苯甲醛、对硝基苯甲醛、4-联苯甲醛、间苯氧基苯甲醛、4-甲磺酰基苯甲醛、4-羧基苯甲醛、3，4-二甲基苯甲醛、2-萘甲醛、3-吲哚基甲醛、2-噻吩基甲醛、2-吡咯基甲醛、2-吡啶基甲醛、3-吡啶基甲醛、苯并咪唑-2-甲醛、N-乙基-咔啉基-3-甲醛以及如下所示结构式中任意一种。
优选的，在步骤(1)中所述溶剂为甲苯、二氧六环、水、二甲亚砜、乙腈、甲醇中的一种或其中几种的混合溶剂。
优选的，所述的式(Ⅲ)，为以下β-咔啉类化合物中任意一种：
优选的，一种天然产物Eudistomin U的制备方法具体制备步骤如下：
(1)将色胺或色胺盐酸盐10mmol、3-吲哚甲醛12mmol以及三苯碳四(五氟苯基)硼酸盐1mmol催化剂依次加入至反应器中，然后加入甲苯或二甲苯有机溶剂，置换氧气保护，置于120℃加热搅拌反应12小时，TLC检测，反应完毕，加DCM萃取3次，干燥，分离纯化得天然产物Eudistomin U。
本发明克服现有技术的不足，提供一种β-咔啉类化合物及其制备方法，相比于现有技术的缺点和不足，本发明具有以下有益效果：
(1)本发明制备方法中所需反应原料(色胺或者其衍生物与芳香醛或其衍生物)廉价易得，一步法得到芳香性的β-咔啉类化合物，与现有的多步合成方法相比条件温和，操作简单，成本低，反应效率高，原子经济性高，可有效降低化学废料的产生。
(2)本发明制备方法中所需的催化剂为非金属类型的催化剂，与现有的金属催化的合成方法相比，合成过程更易于纯化，不存在金属残留的问题。作为医药中间体，不存在金属残留导致的生物毒性。
(3)本发明制备方法中所需的氧化剂为氧气，相比较传统的氧化剂如TEMPO、DDQ、H2O2、高碘盐、二氧化锰等，产生的化学废料更少，更加绿色环保。
(4)本发明制备方法中，对于底物官能团的兼容性，相比较现有的合成方法，合成底物范围更广，具有良好的普适性，且可以以克级规模合成天然产物Eudistomin U。
(5)在步骤(2)中所述加热温度为120℃，反应时间为12小时，气体氛围的对比显示，氧气是必须的反应物；另外随着反应温度的降低，则不利于目标产物的生成。步骤(1)中所述溶剂为甲苯，其他溶剂替代甲苯作为反应溶剂，目标产物的产率均出现不同程度的下降甚至使得催化剂失去催化活性。色胺或色胺衍生物、芳香醛衍生物、离子对催化剂以及溶剂的摩尔体积比为：0.2mmol:0.3mmol:0.04mmol:1mL，为最佳反应条件，降低催化剂的用量，目标产物的产率也开始相应的降低。
(6)用其他离子对催化剂代替Ph3C+[B(C6F5)4]-作为反应的催化剂，则反应效果出现不同程度的下降，甚至失去催化效果。
附图说明
图1化合物21的核磁氢谱(1H NMR 400MHz,CDCl3)
图2化合物21的核磁碳谱(13C NMR 100MHz,CDCl3)
图3化合物24的核磁氢谱(1H NMR 400MHz,CDCl3)
图4化合物24的核磁碳谱(13C NMR 100MHz,CDCl3)
图5化合物33的核磁氢谱(1H NMR 400MHz,CDCl3)
图6化合物33的核磁碳谱(13C NMR 100MHz,CDCl3)
图7化合物34的核磁氢谱(1H NMR 400MHz,CDCl3)
图8化合物34的核磁碳谱(13C NMR 100MHz,CDCl3)
具体实施方式
下面结合实施实例对本发明作进一步详细、完整的说明，列出的实施实例将有助于理解本发明，但不应将此理解为本发明上述主题的范围仅限于以下的实例，凡基于本发明上述内容所实现的技术均属于本发明的范围。
一般说明：
实施实例中使用了缩写，其含义如下：
Me是甲基，tBu是叔丁基，Ph是苯基，THF是四氢呋喃，DCM是二氯甲烷，PE是石油醚，EA是乙酸乙酯。TLC是薄层色谱，NMR是核磁共振，HRMS是高分辨质谱。
所用溶剂在使用前用标准方法提纯，干燥；所用试剂均为市售或按照已有文献方法合成得到，并在使用前提纯。
实施例1：
β-咔啉类化合物的制备方法：取25mL Schlenk管，配置合适大小的搅拌磁子，依次精确称量Ph3C+[B(C6F5)4]-36.8mg，色胺化合物0.2mmol,苯甲醛0.3mmol,反应体系置换氧气3次，加入甲苯1mL,密封后置于120℃加热剧烈搅拌12小时至完全反应。二氯甲烷萃取三次，无水硫酸钠或者无水硫酸镁干燥，过滤，减压浓缩有机溶剂，经硅胶柱层析纯化，得到目标化合物41.5mg，产率85％。
1-phenyl-9H-pyrido[3,4-b]indole 1
As a yellow solid:Rf0.55(EA:PE＝1:5)；
1H NMR(400MHz；CDCl3):δ8.63(s,1H),8.56(d,J＝5.3Hz,1H),8.15(d,J＝7.8Hz,1H),7.95(t,J＝1.7Hz,1H),7.95-7.92(m,2H),7.59-7.52(m,3H),7.50-7.45(m,2H),7.30(ddd,J＝8.0,7.0,1.1Hz,1H)；
13C NMR(101MHz,CDCl3)δ142.65,141.66,138.83,138.80,133.51,129.74,129.28,129.08,128.92,128.73,122.15,121.33,120.06,114.46,112.97.
实施例2：
β-咔啉类化合物的制备方法：取25mL Schlenk管，配置合适大小的搅拌磁子，依次精确称量Ph3C+[B(C6F5)4]-36.8mg，色胺化合物0.2mmol,2-甲基苯甲醛0.3mmol,反应体系置换氧气3次，加入甲苯1mL,密封后置于120℃加热剧烈搅拌12小时至完全反应。二氯甲烷萃取三次，无水硫酸钠或者无水硫酸镁干燥，过滤，减压浓缩有机溶剂，经硅胶柱层析纯化，得到目标化合物37.6mg，产率73％。
1-(o-tolyl)-9H-pyrido[3,4-b]indole 2
As a yellow solid:Rf0.50(EA:PE＝1:5)；
1H NMR(400MHz,CDCl3)δ8.55(d,J＝5.3Hz,1H),8.18(d,J＝8.9Hz,1H),8.14(s,1H),7.96(d,J＝4.6Hz,1H),7.54(ddd,J＝8.3,7.1,1.2Hz,1H),7.50(d,J＝7.0Hz,1H),7.44(d,J＝8.2Hz,1H),7.40(dd,J＝3.9,1.3Hz,2H),7.36(dd,J＝7.4,3.7Hz,1H),7.33-7.28(m,1H),2.26(s,3H).
13C NMR(101MHz,CDCl3)δ144.25,140.28,139.08,137.08,136.68,134.31,131.19,129.36,129.23,128.99,128.60,126.24,122.00,120.30,113.80,111.58,100.37,19.82.
实施例3：
β-咔啉类化合物的制备方法：取25mL Schlenk管，配置合适大小的搅拌磁子，依次精确称量Ph3C+[B(C6F5)4]-36.8mg，色胺化合物0.2mmol,3-甲基苯甲醛0.3mmol,反应体系置换氧气3次，加入甲苯1mL,密封后置于120℃加热剧烈搅拌12小时至完全反应。二氯甲烷萃取三次，无水硫酸钠或者无水硫酸镁干燥，过滤，减压浓缩有机溶剂，经硅胶柱层析纯化，得到目标化合物40.2mg，产率78％。
1-(m-tolyl)-9H-pyrido[3,4-b]indole 3
As a yellow solid:Rf0.50(EA:PE＝1:5)；
1H NMR(400MHz,CDCl3)δ8.60(s,1H),8.55(d,J＝5.2Hz,1H),8.16(d,J＝7.8Hz,1H),7.93(s,1H),7.86(d,J＝8.0Hz,2H),7.55(t,J＝7.6Hz,1H),7.49(d,J＝8.1Hz,1H),7.39(s,2H),7.31(t,J＝7.4Hz,1H),2.45(s,3H).
13C NMR(101MHz,CDCl3)δ143.28,140.44,139.46,139.15,138.45,133.59,129.83,129.70,129.05,129.02,128.53,125.08,121.94,121.89,120.28,113.82,111.68,21.67.
实施例4：
β-咔啉类化合物的制备方法：取25mL Schlenk管，配置合适大小的搅拌磁子，依次精确称量Ph3C+[B(C6F5)4]-36.8mg，色胺化合物0.2mmol,4-甲基苯甲醛化合物0.3mmol,反应体系置换氧气3次，加入甲苯1mL,密封后置于120℃加热剧烈搅拌12小时至完全反应。二氯甲烷萃取三次，无水硫酸钠或者无水硫酸镁干燥，过滤，减压浓缩有机溶剂，经硅胶柱层析纯化，得到目标化合物39.2mg，产率76％。
1-(p-tolyl)-9H-pyrido[3,4-b]indole 4
As a yellow solid:Rf0.52(EA:PE＝1:5)；
1H NMR(400MHz,CDCl3)δ8.71(s,1H),8.54(d,J＝5.2Hz,1H),8.15(d,J＝7.9Hz,1H),7.91(d,J＝5.2Hz,1H),7.84(d,J＝8.1Hz,2H),7.57-7.52(m,1H),7.48(d,J＝8.2Hz,1H),7.36(d,J＝8.1Hz,2H),7.30(ddd,J＝8.1,6.9,1.2Hz,1H),2.44(s,3H).
13C NMR(101MHz,CDCl3)δ183.65,182.47,143.24,140.40,139.54,138.84,135.75,133.55,129.95,129.77,128.49,128.06,122.00,121.87,120.26,113.64,111.62,21.48.
实施例5：
β-咔啉类化合物的制备方法：取25mL Schlenk管，配置合适大小的搅拌磁子，依次精确称量Ph3C+[B(C6F5)4]-36.8mg，色胺化合物0.2mmol,4-甲氧基苯甲醛化合物0.3mmol,反应体系置换氧气3次，加入甲苯1mL,密封后置于120℃加热剧烈搅拌12小时至完全反应。二氯甲烷萃取三次，无水硫酸钠或者无水硫酸镁干燥，过滤，减压浓缩有机溶剂，经硅胶柱层析纯化，得到目标化合物36.8mg，产率67％。
1-(4-methoxyphenyl)-9H-pyrido[3,4-b]indole 5
As a yellow solid:Rf0.52(EA:PE＝1:5)；
1H NMR(400MHz,CDCl3)δ8.55(d,J＝5.3Hz,2H),8.16(d,J＝7.8Hz,1H),7.92(d,J＝8.7Hz,3H),7.59-7.48(m,2H),7.31(ddd,J＝8.0,6.9,1.3Hz,1H),7.11(d,J＝8.8Hz,1H),3.90(s,3H).
13C NMR(101MHz,DMSO-d6)δ154.22,143.33,140.46,138.60,136.58,134.28,133.19,130.22,129.23,121.58,119.17,115.19,114.38,111.35,103.44,57.20.
实施例6：
β-咔啉类化合物的制备方法：取25mL Schlenk管，配置合适大小的搅拌磁子，依次精确称量Ph3C+[B(C6F5)4]-36.8mg，色胺化合物0.2mmol,2-氟苯甲醛化合物0.3mmol,反应体系置换氧气3次，加入甲苯1mL,密封后置于120℃加热剧烈搅拌12小时至完全反应。二氯甲烷萃取三次，无水硫酸钠或者无水硫酸镁干燥，过滤，减压浓缩有机溶剂，经硅胶柱层析纯化，得到目标化合物35.2mg，产率67％。
1-(2-fluorophenyl)-9H-pyrido[3,4-b]indole 6
As a bright yellow solid:Rf0.40(EA:PE＝1:5)；
1H NMR(400MHz,CDCl3)δ8.61(d,J＝6.5Hz,1H),8.38(bs,1H),8.17(d,J＝7.8Hz,1H),8.01(d,J＝6.5Hz,1H),7.89(t,J＝7.6Hz,1H),7.57(d,J＝15.3Hz,1H),7.50(t,J＝7.1Hz,2H),7.37(t,J＝7.5Hz,1H),7.31(t,J＝8.1Hz,2H).
13C NMR(101MHz,CDCl3)δ140.35,140.04,139.63,132.37,132.33,130.77,129.87,128.75,125.26,125.23,121.87,120.32,116.30,116.08,114.42,113.23,111.64.
19F NMR(376MHz,CDCl3)δ-118.3.
实施例7：
β-咔啉类化合物的制备方法：取25mL Schlenk管，配置合适大小的搅拌磁子，依次精确称量Ph3C+[B(C6F5)4]-36.8mg，色胺化合物0.2mmol,3-氟苯甲醛化合物0.3mmol,反应体系置换氧气3次，加入甲苯1mL,密封后置于120℃加热剧烈搅拌12小时至完全反应。二氯甲烷萃取三次，无水硫酸钠或者无水硫酸镁干燥，过滤，减压浓缩有机溶剂，经硅胶柱层析纯化，得到目标化合物44.4mg，产率85％。
1-(3-fluorophenyl)-9H-pyrido[3,4-b]indole 7
As a bright yellow solid:Rf0.45(EA:PE＝1:5)；
1H NMR(400MHz,CDCl3)δ8.65(s,1H),8.56(d,J＝5.2Hz,1H),8.17(d,J＝7.9Hz,1H),7.96(d,J＝5.2Hz,1H),7.75(d,J＝6.4Hz,1H),7.71-7.65(m,1H),7.60-7.50(m,3H),7.36-7.30(m,1H),7.17(td,J＝8.6,3.1Hz,1H).
13C NMR(101MHz,CDCl3)δ163.43(d,J＝247.2Hz),140.90,140.46,139.68,130.87(d,J＝8.4Hz),130.26,128.80,123.76(d,J＝3.3Hz),121.93,121.90,120.54,115.83(d,J＝21.2Hz),115.28(d,J＝22.3Hz),114.36,100.00.
19F NMR(376MHz,CDCl3)δ-118.3.
实施例8：
β-咔啉类化合物的制备方法：取25mL Schlenk管，配置合适大小的搅拌磁子，依次精确称量Ph3C+[B(C6F5)4]-36.8mg，色胺化合物0.2mmol,4-氟苯甲醛化合物0.3mmol,反应体系置换氧气3次，加入甲苯1mL,密封后置于120℃加热剧烈搅拌12小时至完全反应。二氯甲烷萃取三次，无水硫酸钠或者无水硫酸镁干燥，过滤，减压浓缩有机溶剂，经硅胶柱层析纯化，得到目标化合物38.8mg，产率74％。
1-(4-fluorophenyl)-9H-pyrido[3,4-b]indole 8
As a bright yellow solid:Rf0.42(EA:PE＝1:5)；
1H NMR(400MHz,DMSO-d6)δ11.40(s,1H),8.47(d,J＝5.2Hz,1H),8.28(d,J＝7.9Hz,1H),8.18(d,J＝5.2Hz,1H),7.75(td,J＝7.6,1.7Hz,1H),7.64-7.50(m,3H),7.48-7.39(m,2H),7.26(ddd,J＝8.1,6.7,1.4Hz,1H).
13C NMR(101MHz,DMSO-d6)δ161.51,159.05,141.96,138.73,138.61,135.05,133.07,132.42,132.38,131.30,131.22,130.67,128.97,128.85,126.70,126.55,125.29,125.26,114.35,112.66.
19F NMR(376MHz,DMSO-d6))δ-113.64.
实施例9：
β-咔啉类化合物的制备方法：取25mL Schlenk管，配置合适大小的搅拌磁子，依次精确称量Ph3C+[B(C6F5)4]-36.8mg，色胺化合物0.2mmol,4-氯苯甲醛化合物0.3mmol,反应体系置换氧气3次，加入甲苯1mL,密封后置于120℃加热剧烈搅拌12小时至完全反应。二氯甲烷萃取三次，无水硫酸钠或者无水硫酸镁干燥，过滤，减压浓缩有机溶剂，经硅胶柱层析纯化，得到目标化合物43.4mg，产率78％。
1-(4-chlorophenyl)-9H-pyrido[3,4-b]indole 9
As a yellow solid:Rf0.40(EA:PE＝1:5)；
1H NMR(400MHz,CDCl3)δ8.61(s,1H),8.56(d,J＝5.2Hz,1H),8.17(d,J＝7.9Hz,1H),7.95(d,J＝5.2Hz,1H),7.90(d,J＝8.4Hz,2H),7.60-7.48(m,4H),7.33(t,J＝7.4Hz,1H).
13C NMR(101MHz,CDCl3)δ142.64,140.47,139.71,136.66,134.92,133.50,130.21,129.50,128.80,121.96,114.20,111.69.
实施例10：
β-咔啉类化合物的制备方法：取25mL Schlenk管，配置合适大小的搅拌磁子，依次精确称量Ph3C+[B(C6F5)4]-36.8mg，色胺化合物0.2mmol,4-溴苯甲醛化合物0.3mmol,反应体系置换氧气3次，加入甲苯1mL,密封后置于120℃加热剧烈搅拌12小时至完全反应。二氯甲烷萃取三次，无水硫酸钠或者无水硫酸镁干燥，过滤，减压浓缩有机溶剂，经硅胶柱层析纯化，得到目标化合物39.8mg，产率62％。
1-(4-bromophenyl)-9H-pyrido[3,4-b]indole 10
As a bright yellow solid:Rf0.50(EA:PE＝1:5)；
1H NMR(400MHz,CDCl3)δ8.62(s,1H),8.55(d,J＝5.2Hz,1H),8.17(d,J＝7.8Hz,1H),7.95(d,J＝5.2Hz,1H),7.83(d,J＝8.4Hz,2H),7.68(d,J＝8.3Hz,2H),7.59-7.49(m,2H),7.33(t,J＝7.5Hz,1H).
13C NMR(101MHz,CDCl3)δ141.79,140.47,139.71,137.50,133.46,132.41,130.22,129.77,128.79,123.14,121.95,120.54,114.22,111.68,100.00.
实施例11：
β-咔啉类化合物的制备方法：取25mL Schlenk管，配置合适大小的搅拌磁子，依次精确称量Ph3C+[B(C6F5)4]-36.8mg，色胺化合物0.2mmol,4-氰基苯甲醛化合物0.3mmol,反应体系置换氧气3次，加入甲苯1mL,密封后置于120℃加热剧烈搅拌12小时至完全反应。二氯甲烷萃取三次，无水硫酸钠或者无水硫酸镁干燥，过滤，减压浓缩有机溶剂，经硅胶柱层析纯化，得到目标化合物44.6mg，产率83％。
4-(9H-pyrido[3,4-b]indol-1-yl)benzonitrile 11
As a yellow solid:Rf0.30(EA:PE＝1:5)；
1H NMR(400MHz,CDCl3)δ8.61(d,J＝5.2Hz,1H),8.55(s,1H),8.18(dd,J＝7.9,1.0Hz,1H),8.12(d,J＝8.5Hz,2H),8.01(dd,J＝5.2,0.8Hz,1H),7.87(d,J＝8.5Hz,2H),7.62-7.52(m,2H),7.35(ddd,J＝8.0,6.9,1.0Hz,1H).
13C NMR(101MHz,CDCl3)δ143.18,140.51,140.05,133.63,133.07,130.73,129.12,128.88,122.01,121.81,120.85,118.81,114.98,112.34,111.75,100.00.
实施例12：
β-咔啉类化合物的制备方法：取25mL Schlenk管，配置合适大小的搅拌磁子，依次精确称量Ph3C+[B(C6F5)4]-36.8mg，色胺化合物0.2mmol,4-硝基苯甲醛化合物0.3mmol,反应体系置换氧气3次，加入甲苯1mL,密封后置于120℃加热剧烈搅拌12小时至完全反应。二氯甲烷萃取三次，无水硫酸钠或者无水硫酸镁干燥，过滤，减压浓缩有机溶剂，经硅胶柱层析纯化，得到目标化合物38.8mg，产率67％。
1-(4-nitrophenyl)-9H-pyrido[3,4-b]indole 12
As a bright yellow solid:Rf0.20(EA:PE＝1:5)；
1H NMR(400MHz,CDCl3)δ8.62(d,J＝5.2Hz,1H),8.59(s,1H),8.43(d,J＝8.8Hz,2H),8.18(dd,J＝8.9,2.3Hz,3H),8.03(d,J＝5.2Hz,1H),7.64-7.52(m,2H),7.36(ddd,J＝8.0,6.9,1.1Hz,1H).
13C NMR(101MHz,DMSO-d6)δ147.65,145.12,141.76,140.00,139.26,133.92,130.42,130.14,129.16,124.40,122.36,121.21,120.39,115.75,112.93.
实施例13：
β-咔啉类化合物的制备方法：取25mL Schlenk管，配置合适大小的搅拌磁子，依次精确称量Ph3C+[B(C6F5)4]-36.8mg，色胺化合物0.2mmol,4-三氟甲基苯甲醛化合物0.3mmol,反应体系置换氧气3次，加入甲苯1mL,密封后置于120℃加热剧烈搅拌12小时至完全反应。二氯甲烷萃取三次，无水硫酸钠或者无水硫酸镁干燥，过滤，减压浓缩有机溶剂，经硅胶柱层析纯化，得到目标化合物50.5mg，产率81％。
1-(4-(trifluoromethyl)phenyl)-9H-pyrido[3,4-b]indole 13
As a pale yellow solid:Rf0.42(EA:PE＝1:5)；
1H NMR(400MHz,CDCl3)δ8.65(s,1H),8.58(d,J＝5.2Hz,1H),8.17(d,J＝8.9Hz,1H),8.04(d,J＝1.1Hz,2H),7.98(dd,J＝5.2,0.8Hz,1H),7.79(d,J＝8.6Hz,2H),7.57(ddd,J＝8.3,7.0,1.2Hz,1H),7.52-7.48(m,1H),7.37-7.30(m,1H).
13C NMR(101MHz,CDCl3)δ141.99,141.26,140.58,139.71,133.65,130.46,128.96,128.54,126.15(q,J＝4.0Hz),124.13(q,J＝273.5Hz),122.00,121.82,120.66,114.67,111.73.
19F NMR(376MHz,CDCl3)δ-62.4.
实施例14：
β-咔啉类化合物的制备方法：取25mL Schlenk管，配置合适大小的搅拌磁子，依次精确称量Ph3C+[B(C6F5)4]-36.8mg，色胺化合物0.2mmol,4-三氟甲氧基苯甲醛化合物0.3mmol,反应体系置换氧气3次，加入甲苯1mL,密封后置于120℃加热剧烈搅拌12小时至完全反应。二氯甲烷萃取三次，无水硫酸钠或者无水硫酸镁干燥，过滤，减压浓缩有机溶剂，经硅胶柱层析纯化，得到目标化合物30.8mg，产率47％。
1-(4-(trifluoromethoxy)phenyl)-9H-pyrido[3,4-b]indole 14
As a yellow solid:Rf0.36(EA:PE＝1:5)；
1H NMR(400MHz,DMSO-d6)δ11.61(s,1H),8.47(d,J＝5.1Hz,1H),8.28(d,J＝7.8Hz,1H),8.19-8.11(m,3H),7.68-7.52(m,4H),7.28(t,J＝7.5Hz,1H).
13C NMR(101MHz,DMSO-d6)δ148.93,141.70,141.19,138.99,138.14,133.56,130.89,129.95,128.88,122.24,121.81,121.32,120.17,119.45,114.85,112.92.
19F NMR(376MHz,CDCl3)δ-57.6.
HRMS(EI)Calcd for C18H12F3N2O:[M+H]+329.0902.Found:m/z 329.0902.
实施例15：
β-咔啉类化合物的制备方法：取25mL Schlenk管，配置合适大小的搅拌磁子，依次精确称量Ph3C+[B(C6F5)4]-36.8mg，色胺化合物0.2mmol,4-甲磺酰基苯甲醛化合物0.3mmol,反应体系置换氧气3次，加入甲苯1mL,密封后置于120℃加热剧烈搅拌12小时至完全反应。二氯甲烷萃取三次，无水硫酸钠或者无水硫酸镁干燥，过滤，减压浓缩有机溶剂，经硅胶柱层析纯化，得到目标化合物44.4mg，产率69％。
1-(4-(methylsulfonyl)phenyl)-9H-pyrido[3,4-b]indole 15
As a bright yellow solid:Rf0.60(EA:PE＝1:2)；
1H NMR(400MHz,DMSO-d6)δ11.69(s,1H),8.52(d,J＝5.1Hz,1H),8.29(dd,J＝8.6,2.2Hz,3H),8.21(d,J＝5.2Hz,1H),8.15(d,J＝8.5Hz,2H),7.65(d,J＝8.2Hz,1H),7.61-7.54(m,1H),7.29(t,J＝7.4Hz,1H),3.33(s,3H).
13C NMR(101MHz,DMSO-d6)δ143.65,141.75,140.94,140.71,139.18,133.87,130.22,129.82,129.06,127.92,122.31,121.25,120.30,115.44,112.93,44.50.
HRMS(EI)Calcd for C18H15N2O2S:[M+H]+323.0854.Found:m/z 323.0855.
实施例16：
β-咔啉类化合物的制备方法：取25mL Schlenk管，配置合适大小的搅拌磁子，依次精确称量Ph3C+[B(C6F5)4]-36.8mg，色胺化合物0.2mmol,4-苯基苯甲醛类化合物0.3mmol,反应体系置换氧气3次，加入甲苯1mL,密封后置于120℃加热剧烈搅拌12小时至完全反应。二氯甲烷萃取三次，无水硫酸钠或者无水硫酸镁干燥，过滤，减压浓缩有机溶剂，经硅胶柱层析纯化，得到目标化合物37.0mg，产率58％。
1-([1,1'-biphenyl]-4-yl)-9H-pyrido[3,4-b]indole 16
As a white solid:Rf 0.40(EA:PE＝1:5)；
1H NMR(400MHz,DMSO-d6)δ11.61(s,1H),8.48(d,J＝5.1Hz,1H),8.28(d,J＝7.9Hz,1H),8.18-8.11(m,3H),7.92(d,J＝8.3Hz,2H),7.80(d,J＝7.2Hz,2H),7.67(d,J＝8.2Hz,1H),7.55(dt,J＝12.9,7.4Hz,3H),7.42(t,J＝7.3Hz,1H),7.28(t,J＝7.5Hz,1H).
13C NMR(101MHz,DMSO-d6)δ142.25,141.67,140.66,140.19,138.99,138.01,133.60,129.78,129.66,129.49,128.74,128.28,127.49,127.23,122.18,121.37,120.09,114.51,112.99.
实施例17：
β-咔啉类化合物的制备方法：取25mL Schlenk管，配置合适大小的搅拌磁子，依次精确称量Ph3C+[B(C6F5)4]-36.8mg，色胺化合物0.2mmol,3,4,5-三氟苯甲醛化合物0.3mmol,反应体系置换氧气3次，加入甲苯1mL,密封后置于120℃加热剧烈搅拌12小时至完全反应。二氯甲烷萃取三次，无水硫酸钠或者无水硫酸镁干燥，过滤，减压浓缩有机溶剂，经硅胶柱层析纯化，得到目标化合物50.0mg，产率84％。
1-(3,4,5-trifluorophenyl)-9H-pyrido[3,4-b]indole 17
As a bright yellow solid:Rf0.38(EA:PE＝1:5)；
1H NMR(400MHz,CDCl3)δ8.71(s,1H),8.54(d,J＝5.2Hz,1H),8.16(d,J＝8.7Hz,1H),7.98(d,J＝5.2Hz,1H),7.63-7.56(m,3H),7.53(d,J＝8.2Hz,1H),7.34(t,J＝7.5Hz,1H).
13C NMR(101MHz,CDCl3)δ154.12-148.87(m),140.65,139.67,133.31,130.82,129.67,129.13,121.98,121.81,120.85,115.50,114.88,112.56-112.19(m),111.82.
19F NMR(376MHz,CDCl3)δ-132.58(dd,J＝20.7,7.7Hz),-159.43(tt,J＝20.6,6.4Hz).
HRMS(EI)Calcd for C17H10F3N2:[M+H]+299.0796.Found:m/z 299.0797.
实施例18：
β-咔啉类化合物的制备方法：取25mL Schlenk管，配置合适大小的搅拌磁子，依次精确称量Ph3C+[B(C6F5)4]-36.8mg，色胺化合物0.2mmol,4-乙烯基苯甲醛化合物0.3mmol,反应体系置换氧气3次，加入甲苯1mL,密封后置于120℃加热剧烈搅拌12小时至完全反应。二氯甲烷萃取三次，无水硫酸钠或者无水硫酸镁干燥，过滤，减压浓缩有机溶剂，经硅胶柱层析纯化，得到目标化合物41.8mg，产率81％。
1-(4-vinylphenyl)-9H-pyrido[3,4-b]indole 18
As a yellow solid:Rf0.50(EA:PE＝1:5)；
1H NMR(400MHz,CDCl3)δ8.71(s,1H),8.56(d,J＝5.2Hz,1H),8.16(d,J＝7.7Hz,1H),7.95-7.89(m,3H),7.61-7.52(m,3H),7.49(d,J＝8.0Hz,1H),7.34-7.29(m,1H),6.79(dd,J＝17.6,10.9Hz,1H),5.84(d,J＝17.6Hz,1H),5.33(d,J＝10.8Hz,1H).
13C NMR(101MHz,CDCl3)δ142.72,140.43,139.63,138.07,137.96,136.40,133.59,129.96,128.60,128.34,127.06,121.96,121.90,120.36,114.83,113.89,111.65.
HRMS(EI)Calcd for C19H15N2:[M+H]+271.1235.Found:m/z 271.1234.
实施例19：
β-咔啉类化合物的制备方法：取25mL Schlenk管，配置合适大小的搅拌磁子，依次精确称量Ph3C+[B(C6F5)4]-36.8mg，色胺化合物0.2mmol,4-炔基苯甲醛化合物0.3mmol,反应体系置换氧气3次，加入甲苯1mL,密封后置于120℃加热剧烈搅拌12小时至完全反应。二氯甲烷萃取三次，无水硫酸钠或者无水硫酸镁干燥，过滤，减压浓缩有机溶剂，经硅胶柱层析纯化，得到目标化合物40.8mg，产率76％。
1-(4-ethynylphenyl)-9H-pyrido[3,4-b]indole 19
As a yellow solid:Rf0.45(EA:PE＝1:5)；
1H NMR(400MHz,CDCl3)δ8.56(d,J＝5.2Hz,2H),8.16(d,J＝7.9Hz,1H),7.97-7.91(m,3H),7.68(d,J＝8.2Hz,2H),7.59-7.48(m,2H),7.34-7.29(m,1H),3.17(s,1H).
13C NMR(101MHz,CDCl3)δ141.96,140.45,139.69,138.91,133.54,133.02,130.22,128.79,128.11,122.58,121.95,121.88,120.52,114.27,111.70,83.43,78.53.
HRMS(EI)Calcd for C19H13N2:[M+H]+269.1079.Found:m/z 269.1075.
实施例20：
β-咔啉类化合物的制备方法：取25mL Schlenk管，配置合适大小的搅拌磁子，依次精确称量Ph3C+[B(C6F5)4]-36.8mg，色胺化合物0.2mmol,苯并呋喃甲醛化合物0.3mmol,反应体系置换氧气3次，加入甲苯1mL,密封后置于120℃加热剧烈搅拌12小时至完全反应。二氯甲烷萃取三次，无水硫酸钠或者无水硫酸镁干燥，过滤，减压浓缩有机溶剂，经硅胶柱层析纯化，得到目标化合物37.6mg，产率66％。
1-(2,3-dihydrobenzofuran-5-yl)-9H-pyrido[3,4-b]indole 20
As a bright yellow solid:Rf0.35(EA:PE＝1:5)；
1H NMR(400MHz,CDCl3)δ8.71(s,1H),8.52(d,J＝5.3Hz,1H),8.15(d,J＝7.9Hz,1H),7.89(d,J＝5.3Hz,1H),7.80(s,1H),7.70(dd,J＝8.2,2.0Hz,1H),7.58-7.47(m,2H),7.35-7.27(m,1H),6.93(d,J＝8.2Hz,1H),4.64(t,J＝8.7Hz,2H),3.27(t,J＝8.7Hz,2H).
13C NMR(101MHz,CDCl3)δ160.41,143.38,140.40,139.04,133.38,131.13,130.12,128.47,128.00,125.26,122.06,121.89,119.86,113.31,111.66,109.70,71.24,31.42.
HRMS(EI)Calcd for C19H14N2O:[M+H]+286.1106.Found:m/z 286.1104.
实施例21：
β-咔啉类化合物的制备方法：取25mL Schlenk管，配置合适大小的搅拌磁子，依次精确称量Ph3C+[B(C6F5)4]-36.8mg，色胺化合物0.2mmol,萘甲醛化合物0.3mmol,反应体系置换氧气3次，加入甲苯1mL,密封后置于120℃加热剧烈搅拌12小时至完全反应。二氯甲烷萃取三次，无水硫酸钠或者无水硫酸镁干燥，过滤，减压浓缩有机溶剂，经硅胶柱层析纯化，得到目标化合物39.4mg，产率67％。
1-(naphthalen-2-yl)-9H-pyrido[3,4-b]indole 21
As a bright yellow solid:Rf0.45(EA:PE＝1:5)；
1H NMR(400MHz,CDCl3)δ8.74(s,1H),8.63(d,J＝5.3Hz,1H),8.39(s,1H),8.19(d,J＝7.5Hz,1H),8.11-8.00(m,2H),8.00-7.89(m,3H),7.62-7.51(m,4H),7.33(ddd,J＝8.0,6.7,1.3Hz,1H).
13C NMR(101MHz,CDCl3)δ143.04,141.29,140.47,139.78,136.03,133.58,133.47,130.01,129.19,128.64,128.46,127.97,127.28,126.76,126.65,125.96,122.03,121.95,120.41,113.93,111.68.
实施例22：
β-咔啉类化合物的制备方法：取25mL Schlenk管，配置合适大小的搅拌磁子，依次精确称量Ph3C+[B(C6F5)4]-36.8mg，色胺化合物0.2mmol,吲哚-3-甲醛化合物0.3mmol,反应体系置换氧气3次，加入甲苯1mL,密封后置于120℃加热剧烈搅拌12小时至完全反应。二氯甲烷萃取三次，无水硫酸钠或者无水硫酸镁干燥，过滤，减压浓缩有机溶剂，经硅胶柱层析纯化，得到目标化合物23.8mg，产率42％。
1-(1H-indol-3-yl)-9H-pyrido[3,4-b]indole 22
As a dark yellow solid:Rf0.65(EA:PE＝1:2)；
1H NMR(400MHz,CDCl3)δ9.42(s,1H),8.56(d,J＝5.2Hz,2H),8.51(s,2H),8.16(d,J＝7.7Hz,2H),7.97(d,J＝7.6Hz,2H),7.89(d,J＝5.4Hz,2H),7.53(dd,J＝7.3,1.6Hz,2H),7.45(d,J＝8.1Hz,1H),7.39(d,J＝8.2Hz,1H),7.31(t,J＝7.4Hz,1H),7.25-7.19(m,2H).
13C NMR(101MHz,CDCl3)δ140.28,139.34,138.84,136.65,133.78,129.27,128.42,125.81,124.82,122.84,122.06,121.89,120.92,120.52,120.23,112.82,111.96,111.74,100.00.
实施例23：
β-咔啉类化合物的制备方法：取25mL Schlenk管，配置合适大小的搅拌磁子，依次精确称量Ph3C+[B(C6F5)4]-36.8mg，色胺化合物0.2mmol,噻吩-2-甲醛化合物0.3mmol,反应体系置换氧气3次，加入甲苯1mL,密封后置于120℃加热剧烈搅拌12小时至完全反应。二氯甲烷萃取三次，无水硫酸钠或者无水硫酸镁干燥，过滤，减压浓缩有机溶剂，经硅胶柱层析纯化，得到目标化合物30.0mg，产率60％。
1-(thiophen-2-yl)-9H-pyrido[3,4-b]indole 23
As a bright yellow solid:Rf0.35(EA:PE＝1:5)；
1H NMR(400MHz,CDCl3)δ8.77(s,1H),8.49(d,J＝5.1Hz,1H),8.13(d,J＝7.9Hz,1H),7.88(d,J＝5.2Hz,1H),7.75(d,J＝3.7Hz,1H),7.59-7.48(m,3H),7.32(ddd,J＝8.0,6.1,2.0Hz,1H),7.22(dd,J＝5.2,3.5Hz,1H).
13C NMR(101MHz,CDCl3)δ142.97,140.59,139.43,137.15,132.32,130.47,128.76,128.13,127.30,125.13,121.96,121.86,120.65,113.88,111.84.
实施例24：
β-咔啉类化合物的制备方法：取25mL Schlenk管，配置合适大小的搅拌磁子，依次精确称量Ph3C+[B(C6F5)4]-36.8mg，色胺化合物0.2mmol,吡啶-3-甲醛化合物0.3mmol,反应体系置换氧气3次，加入甲苯1mL,密封后置于120℃加热剧烈搅拌12小时至完全反应。二氯甲烷萃取三次，无水硫酸钠或者无水硫酸镁干燥，过滤，减压浓缩有机溶剂，经硅胶柱层析纯化，得到目标化合物43.6mg，产率89％。
1-(pyridin-3-yl)-9H-pyrido[3,4-b]indole 24
As a bright yellow solid:Rf0.55(EA:PE＝1:2)；
1H NMR(400MHz,CDCl3)δ10.36(s,1H),9.44(dd,J＝2.2,0.9Hz,1H),8.63(dd,J＝4.8,1.7Hz,1H),8.60(d,J＝5.2Hz,1H),8.36(dt,J＝7.9,2.0Hz,1H),8.18(d,J＝7.0Hz,1H),8.01(d,J＝5.2Hz,1H),7.59-7.52(m,2H),7.51(ddd,J＝7.7,4.8,0.9Hz,1H),7.32(ddd,J＝8.1,6.0,2.1Hz,1H).
13C NMR(101MHz,CDCl3)δ149.05,148.74,141.43,139.56,136.93,135.34,134.22,130.50,128.82,124.61,121.84,121.63,120.28,114.67,111.97.
实施例25：
β-咔啉类化合物的制备方法：取25mL Schlenk管，配置合适大小的搅拌磁子，依次精确称量Ph3C+[B(C6F5)4]-36.8mg，5-甲基色胺化合物0.2mmol,4-氰基苯甲醛化合物0.3mmol,反应体系置换氧气3次，加入甲苯1mL,密封后置于120℃加热剧烈搅拌12小时至完全反应。二氯甲烷萃取三次，无水硫酸钠或者无水硫酸镁干燥，过滤，减压浓缩有机溶剂，经硅胶柱层析纯化，得到目标化合物23.2mg，产率41％。
4-(6-methyl-9H-pyrido[3,4-b]indol-1-yl)benzonitrile 25
As a bright yellow solid:Rf0.65(EA:PE＝1:2)；
1H NMR(400MHz,CDCl3)δ8.57(d,J＝5.2Hz,1H),8.48(s,1H),8.15-8.09(m,2H),7.97(d,J＝4.4Hz,2H),7.89-7.82(m,2H),7.45-7.38(m,2H),2.56(s,3H).
13C NMR(101MHz,CDCl3)δ143.22,141.17,139.79,138.81,135.06,133.05,130.67,130.59,130.37,128.87,121.95,121.71,118.19,115.36,112.67,110.99,22.04.
HRMS(EI)Calcd for C19H13N3:[M+H]+283.1109.Found:m/z 283.1109.
实施例26：
β-咔啉类化合物的制备方法：取25mL Schlenk管，配置合适大小的搅拌磁子，依次精确称量Ph3C+[B(C6F5)4]-36.8mg，5-甲氧基色胺化合物0.2mmol,4-氰基苯甲醛化合物0.3mmol,反应体系置换氧气3次，加入甲苯1mL,密封后置于120℃加热剧烈搅拌12小时至完全反应。二氯甲烷萃取三次，无水硫酸钠或者无水硫酸镁干燥，过滤，减压浓缩有机溶剂，经硅胶柱层析纯化，得到目标化合物27.0mg，产率45％。
4-(6-methoxy-9H-pyrido[3,4-b]indol-1-yl)benzonitrile 26
As a bright yellow solid:Rf0.55(EA:PE＝1:2)；
1H NMR(400MHz,DMSO-d6)δ11.51(s,1H),8.47(d,J＝5.2Hz,1H),8.26-8.16(m,3H),8.06(d,J＝8.3Hz,1H),7.84(d,J＝2.5Hz,1H),7.55(d,J＝8.8Hz,1H),7.22(dd,J＝8.9,2.4Hz,1H),3.88(s,3H).
13C NMR(101MHz,DMSO-d6)δ154.20,143.31,140.44,138.58,136.57,134.26,133.17,130.21,129.67,121.56,119.45,119.16,115.56,113.79,111.34,103.94,56.13.
实施例27：
β-咔啉类化合物的制备方法：取25mL Schlenk管，配置合适大小的搅拌磁子，依次精确称量Ph3C+[B(C6F5)4]-36.8mg，5-氯色胺化合物0.2mmol,4-氰基苯甲醛化合物0.3mmol,反应体系置换氧气3次，加入甲苯1mL,密封后置于120℃加热剧烈搅拌12小时至完全反应。二氯甲烷萃取三次，无水硫酸钠或者无水硫酸镁干燥，过滤，减压浓缩有机溶剂，经硅胶柱层析纯化，得到目标化合物31.6mg，产率52％。
4-(6-chloro-9H-pyrido[3,4-b]indol-1-yl)benzonitrile 27
As a bright yellow solid:Rf0.50(EA:PE＝1:2)；
1H NMR(400MHz,DMSO-d6)δ11.83(s,1H),8.53(d,J＝5.2Hz,1H),8.45(d,J＝2.0Hz,1H),8.26(d,J＝5.2Hz,1H),8.21(d,J＝8.4Hz,2H),8.08(d,J＝8.3Hz,2H),7.65(d,J＝8.7Hz,1H),7.59(dd,J＝8.7,2.1Hz,1H).
13C NMR(101MHz,DMSO-d6)δ156.85,142.99,140.11,139.75,139.42,134.25,133.24,129.76,129.42,129.01,124.60,122.52,121.95,121.92,119.40,100.00.
实施例28：
β-咔啉类化合物的制备方法：取25mL Schlenk管，配置合适大小的搅拌磁子，依次精确称量Ph3C+[B(C6F5)4]-36.8mg，5-溴色胺化合物0.2mmol,4-氰基苯甲醛化合物0.3mmol,反应体系置换氧气3次，加入甲苯1mL,密封后置于120℃加热剧烈搅拌12小时至完全反应。二氯甲烷萃取三次，无水硫酸钠或者无水硫酸镁干燥，过滤，减压浓缩有机溶剂，经硅胶柱层析纯化，得到目标化合物32.6mg，产率74％。
4-(6-bromo-9H-pyrido[3,4-b]indol-1-yl)benzonitrile 28
As a pale yellow solid:Rf0.30(EA:PE＝1:5)；
1H NMR(400MHz,DMSO-d6)δ11.80(s,1H),8.55(d,J＝2.0Hz,1H),8.50(d,J＝5.2Hz,1H),8.24(d,J＝5.1Hz,1H),8.20-8.12(m,2H),8.08-7.98(m,2H),7.67(dd,J＝8.7,2.0Hz,1H),7.57(d,J＝8.7Hz,1H).
13C NMR(101MHz,DMSO-d6)δ143.00,140.94,140.40,139.48,134.08,133.25,131.57,130.43,129.32,124.96,123.19,120.24,116.80,115.35,113.00,111.58.
实施例29：
β-咔啉类化合物的制备方法：取25mL Schlenk管，配置合适大小的搅拌磁子，依次精确称量Ph3C+[B(C6F5)4]-36.8mg，5-甲氧-2-甲基色胺化合物0.2mmol,4-氰基苯甲醛化合物0.3mmol,反应体系置换氧气3次，加入甲苯1mL,密封后置于120℃加热剧烈搅拌12小时至完全反应。二氯甲烷萃取三次，无水硫酸钠或者无水硫酸镁干燥，过滤，减压浓缩有机溶剂，经硅胶柱层析纯化，得到目标化合物45.6mg，产率73％。
4-(6-methoxy-3-methyl-9H-pyrido[3,4-b]indol-1-yl)benzonitrile 29
As a yellow solid:Rf0.45(EA:PE＝1:5)；
1H NMR(400MHz,CDCl3)δ8.32(s,1H),8.08(d,J＝8.3Hz,2H),7.83-7.78(m,3H),7.55(d,J＝2.5Hz,1H),7.40(d,J＝8.9Hz,1H),7.20(dd,J＝8.9,2.5Hz,1H),3.94(s,3H),2.78(s,3H).
13C NMR(101MHz,CDCl3)δ154.48,148.72,143.85,140.45,136.69,132.95,132.80,131.66,129.30,122.08,118.94,118.87,114.37,112.59,111.99,103.69,57.70,25.22.
实施例30：
β-咔啉类化合物的制备方法：取25mL Schlenk管，配置合适大小的搅拌磁子，依次精确称量Ph3C+[B(C6F5)4]-36.8mg，2-乙酯基色胺化合物0.2mmol,苯甲醛化合物0.3mmol,反应体系置换氧气3次，加入甲苯1mL,密封后置于120℃加热剧烈搅拌12小时至完全反应。二氯甲烷萃取三次，无水硫酸钠或者无水硫酸镁干燥，过滤，减压浓缩有机溶剂，经硅胶柱层析纯化，得到目标化合物34.2mg，产率54％。
ethyl 1-phenyl-9H-pyrido[3,4-b]indole-3-carboxylate 30
As a yellow solid:Rf0.35(EA:PE＝1:5)；
1H NMR(400MHz,CDCl3)δ9.01(s,1H),8.83(s,1H),8.21(d,J＝7.9Hz,1H),8.13-8.05(m,1H),7.94-7.82(m,2H),7.68-7.50(m,2H),7.49-7.42(m,2H),7.39-7.32(m,1H),4.51(q,J＝7.1Hz,2H),1.46(t,J＝7.1Hz,3H).
13C NMR(101MHz,CDCl3)δ171.00,166.48,143.01,140.26,138.47,137.33,135.15,133.73,130.73,130.25,129.81,129.15,128.47,122.19,122.06,121.12,116.91,112.07,61.27,13.40.
实施例31：
β-咔啉类化合物的制备方法：取25mL Schlenk管，配置合适大小的搅拌磁子，依次精确称量Ph3C+[B(C6F5)4]-36.8mg，色胺化合物0.2mmol,丙叉保护的葡萄糖类衍生物0.3mmol,反应体系置换氧气3次，加入甲苯1mL,密封后置于120℃加热剧烈搅拌12小时至完全反应。二氯甲烷萃取三次，无水硫酸钠或者无水硫酸镁干燥，过滤，减压浓缩有机溶剂，经硅胶柱层析纯化，得到目标化合物82.6mg，产率78％。
((5R,5aS,8aS,8bR)-2,2,7,7-tetramethyltetrahydro-5H-bis([1,3]dioxolo)[4,5-b:4',5'-d]pyran-5-yl)methyl4-(9H-pyrido[3,4-b]indol-1-yl)benzoate 31
As a pale yellow solid:Rf0.65(EA:PE＝1:2)；
1H NMR(400MHz,CDCl3)δ8.88(s,1H),8.56(d,J＝5.2Hz,1H),8.27-8.11(m,3H),8.04-7.90(m,3H),7.65-7.47(m,2H),7.31(ddd,J＝8.0,5.8,2.3Hz,1H),5.58(d,J＝4.9Hz,1H),4.66(dd,J＝7.9,2.5Hz,1H),4.56(dd,J＝11.5,4.6Hz,1H),4.45(dd,J＝11.5,7.7Hz,1H),4.38-4.31(m,2H),4.22(ddd,J＝7.7,4.6,1.9Hz,1H),1.50(d,J＝16.7Hz,6H),1.34(d,J＝10.6Hz,6H).
13C NMR(101MHz,CDCl3)δ166.29,143.09,141.68,140.62,139.71,133.75,130.61,130.35,130.06,128.85,128.21,121.93,121.82,120.53,114.56,111.83,109.84,108.97,96.94,71.22,70.82,70.60,66.29,64.24,26.16,26.08,25.09,24.57.
HRMS(EI)Calcd for C30H30N2O7:[M+H]+530.2053.Found:m/z 530.2049.
实施例32：
β-咔啉类化合物的制备方法：取25mL Schlenk管，配置合适大小的搅拌磁子，依次精确称量Ph3C+[B(C6F5)4]-36.8mg，色胺化合物0.2mmol,苄基保护的豆腐果甙0.3mmol,反应体系置换氧气3次，加入甲苯1mL,密封后置于120℃加热剧烈搅拌12小时至完全反应。二氯甲烷萃取三次，无水硫酸钠或者无水硫酸镁干燥，过滤，减压浓缩有机溶剂，经硅胶柱层析纯化，得到目标化合物104.2mg，产率73％。
1-(4-(((2R,3R,4R,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-yl)oxy)phenyl)-9H-pyrido[3,4-b]indole 33
As a pale yellow solid:Rf 0.50(EA:PE＝1:2)；
1H NMR(400MHz,CDCl3)δ8.68(s,1H),8.55(d,J＝5.2Hz,1H),8.15(d,J＝7.8Hz,1H),7.91(d,J＝5.3Hz,1H),7.83(d,J＝8.6Hz,2H),7.54(ddd,J＝8.3,6.9,1.2Hz,1H),7.47(d,J＝8.2Hz,1H),7.42-7.36(m,6H),7.34-7.27(m,6H),7.26-7.18(m,11H),5.61(d,J＝7.9Hz,1H),4.92(d,J＝12.2Hz,2H),4.83(d,J＝11.9Hz,1H),4.72(d,J＝12.1Hz,1H),4.60(d,J＝12.1Hz,1H),4.56-4.49(m,2H),4.41(d,J＝11.5Hz,1H),4.27(ddd,J＝9.8,4.6,1.9Hz,1H),4.21(t,J＝2.5Hz,1H),3.84(dd,J＝10.9,2.0Hz,1H),3.74(dd,J＝10.8,4.6Hz,1H),3.61(dd,J＝9.8,2.4Hz,1H),3.53(dd,J＝7.9,2.6Hz,1H).
13C NMR(101MHz,CDCl3)δ157.99,142.94,140.46,138.91,138.53,138.27,137.84,133.52,129.38,128.55,128.52,128.40,128.32,128.12,127.96,127.91,127.89,127.85,127.79,127.68,127.59,122.00,121.88,120.22,117.37,113.56,111.72,99.15,78.75,75.38,74.75,74.65,73.59,73.31,72.82,71.71,69.15.
HRMS(EI)Calcd for C51H47N2O6:[M+H]+783.3434.Found:m/z 783.3437.
实施例33：
β-咔啉类化合物的制备方法：取25mL Schlenk管，配置合适大小的搅拌磁子，依次精确称量Ph3C+[B(C6F5)4]-36.8mg，色胺化合物0.2mmol,阿达帕林衍生物0.3mmol,反应体系置换氧气3次，加入甲苯1mL,密封后置于120℃加热剧烈搅拌12小时至完全反应。二氯甲烷萃取三次，无水硫酸钠或者无水硫酸镁干燥，过滤，减压浓缩有机溶剂，经硅胶柱层析纯化，得到目标化合物69.4mg，产率65％。
1-(6-(3-((3r,5r,7r)-adamantan-1-yl)-4-methoxyphenyl)naphthalen-2-yl)-9H-pyrido[3,4-b]indole 32
As a yellow solid:Rf0.25(EA:PE＝1:5)；
1H NMR(400MHz,CDCl3)δ8.87(s,1H),8.61(d,J＝5.2Hz,1H),8.35(d,J＝1.6Hz,1H),8.17(d,J＝7.9Hz,1H),8.08-7.99(m,3H),7.97-7.89(m,2H),7.76(dd,J＝8.5,1.8Hz,1H),7.63(d,J＝2.3Hz,1H),7.59-7.46(m,3H),7.32(ddd,J＝8.0,6.5,1.6Hz,1H),7.00(d,J＝8.5Hz,1H),3.91(s,3H),2.20(d,J＝3.1Hz,6H),2.14-2.07(m,3H),1.81(d,J＝3.2Hz,6H).
13C NMR(101MHz,CDCl3)δ158.81,143.05,140.55,139.80,139.62,139.03,135.49,133.84,132.91,132.32,130.05,129.30,128.83,128.65,127.05,126.41,126.23,125.98,125.73,124.94,122.01,121.96,120.40,113.89,112.18,111.76.
HRMS(EI)Calcd for C38H34N2O:[M+H]+534.2671.Found:m/z 534.2671.
实施例34：
β-咔啉类化合物的制备方法：取25mL Schlenk管，配置合适大小的搅拌磁子，依次精确称量Ph3C+[B(C6F5)4]-36.8mg，色胺化合物0.2mmol,薄荷醇衍生物0.3mmol,反应体系置换氧气3次，加入甲苯1mL,密封后置于120℃加热剧烈搅拌12小时至完全反应。二氯甲烷萃取三次，无水硫酸钠或者无水硫酸镁干燥，过滤，减压浓缩有机溶剂，经硅胶柱层析纯化，得到目标化合物67.4mg，产率79％。
(1S,2R,5S)-2-isopropyl-5-methylcyclohexyl4-(9H-pyrido[3,4-b]indol-1-yl)benzoate 34
As a pale yellow solid:Rf0.40(EA:PE＝1:5)；
1H NMR(400MHz,CDCl3)δ8.93(s,1H),8.59(d,J＝5.2Hz,1H),8.21-8.15(m,3H),8.03(d,J＝8.3Hz,2H),7.98(d,J＝5.2Hz,1H),7.60-7.52(m,2H),7.33(ddd,J＝8.0,6.6,1.5Hz,1H),4.96(td,J＝10.9,4.4Hz,1H),2.11(dd,J＝11.7,2.9Hz,1H),1.97(pd,J＝7.0,2.8Hz,1H),1.77-1.68(m,2H),1.62-1.45(m,2H),1.19-1.05(m,2H),0.92(dd,J＝9.3,6.7Hz,6H),0.81(d,J＝6.9Hz,3H).
13C NMR(101MHz,CDCl3)δ209.77,191.88,165.07,139.48,138.67,135.84,130.80,129.59,122.85,75.30,63.76,56.90,49.94,44.09,38.85,38.16,37.07,36.74,31.89,31.71,27.22,24.58,22.89,21.14,19.46,13.34.
HRMS(EI)Calcd for C28H30N2O2:[M+H]+426.2307.Found:m/z 426.2306.
实施例35：
β-咔啉类化合物的制备方法：取25mL Schlenk管，配置合适大小的搅拌磁子，依次精确称量Ph3C+[B(C6F5)4]-36.8mg，色胺化合物0.2mmol,β-紫罗兰醇衍生物0.3mmol,反应体系置换氧气3次，加入甲苯1mL,密封后置于120℃加热剧烈搅拌12小时至完全反应。二氯甲烷萃取三次，无水硫酸钠或者无水硫酸镁干燥，过滤，减压浓缩有机溶剂，经硅胶柱层析纯化，得到目标化合物59.4mg，产率70％。
(Z)-3,7-dimethylocta-2,6-dien-1-yl 4-(9H-pyrido[3,4-b]indol-1-yl)benzoate 35
As a pale yellow solid:Rf0.35(EA:PE＝1:5)；
1H NMR(400MHz,CDCl3)δ8.81(s,1H),8.58(d,J＝5.2Hz,1H),8.23-8.14(m,3H),8.05-8.00(m,2H),7.98(d,J＝5.2Hz,1H),7.60-7.51(m,2H),7.33(ddd,J＝8.0,6.7,1.3Hz,1H),5.51(t,J＝8.0Hz,1H),5.16-5.08(m,1H),4.84(d,J＝8.3Hz,2H),2.24-2.09(m,4H),1.81(d,J＝1.3Hz,3H),1.68(s,3H),1.61(s,3H).
13C NMR(101MHz,CDCl3)δ166.52,143.04,142.87,141.73,140.58,139.73,133.73,132.40,130.58,130.52,130.35,128.86,128.16,123.65,121.95,121.84,120.56,119.22,114.53,111.78,61.97,32.36,26.78,25.83,24.08,17.81.
HRMS(EI)Calcd for C28H28N2O2:[M+H]+424.2151.Found:m/z 424.2154.
实施例36：
β-咔啉类化合物的制备方法：取25mL Schlenk管，配置合适大小的搅拌磁子，依次精确称量Ph3C+[B(C6F5)4]-36.8mg，色胺化合物0.2mmol,二氢胆固醇衍生物0.3mmol,反应体系置换氧气3次，加入甲苯1mL,密封后置于120℃加热剧烈搅拌12小时至完全反应。二氯甲烷萃取三次，无水硫酸钠或者无水硫酸镁干燥，过滤，减压浓缩有机溶剂，经硅胶柱层析纯化，得到目标化合物61.8mg，产率47％。
(5R,8R,9S,10S,13R,14S,17R)-10,13-dimethyl-17-(R)-6-methylheptan-2-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl 4-(9H-pyrido[3,4-b]indol-1-yl)benzoate 36
As a yellow solid:Rf0.30(EA:PE＝1:5)；
1H NMR(400MHz,CDCl3)δ9.07(s,1H),8.57(d,J＝5.2Hz,1H),8.16(dd,J＝12.7,8.2Hz,3H),8.03-7.95(m,3H),7.57(dd,J＝6.0,1.2Hz,2H),7.33(ddd,J＝8.1,6.0,2.1Hz,1H),4.96-4.86(m,1H),2.00-1.89(m,2H),1.85-1.79(m,1H),1.77-1.71(m,1H),1.70-1.61(m,3H),1.59-1.44(m,4H),1.39-1.28(m,5H),1.27-1.18(m,4H),1.11(dq,J＝16.9,8.0,7.5Hz,7H),1.04-0.93(m,4H),0.91(d,J＝6.5Hz,3H),0.88(d,J＝2.0Hz,3H),0.86(d,J＝1.9Hz,3H),0.85(s,3H),0.65(s,3H).
13C NMR(101MHz,CDCl3)δ166.08,142.77,141.83,140.71,139.66,133.81,130.86,130.38,128.82,128.14,121.94,121.84,120.51,114.51,111.85,74.84,56.51,56.34,54.25,44.70,42.68,40.07,39.61,36.81,36.26,35.91,35.54,34.20,32.05,28.68,28.36,28.13,27.67,24.32,23.94,22.96,22.69,21.29,18.78,12.38,12.17.
HRMS(EI)Calcd for C45H58N2O2:[M+H]+658.4498.Found:m/z 658.4503.
实施例37：
化合物19的克级规模制备方法：取100mL圆底反应瓶，配置合适大小的搅拌磁子，依次精确称量Ph3C+[B(C6F5)4]-(184mg,20mol％)，色胺(1.60g,10mmol,1.0当量),对炔基苯甲醛(12mmol,1.2当量),反应体系置换3次氧气，加入20mL甲苯,密封后置于120℃加热剧烈搅拌12小时至完全反应。二氯甲烷萃取三次，无水硫酸钠或者无水硫酸镁干燥，过滤，减压浓缩有机溶剂，经硅胶柱层析纯化，得到目标化合物1.24g，产率46％。
实施例38：
化合物22(Eudistomin U)的克级规模制备方法：取100mL圆底反应瓶，配置合适大小的搅拌磁子，依次精确称量Ph3C+[B(C6F5)4]-(184mg,20mol％)，色胺(1.60g,10mmol,1.0当量),3-甲酰基吲哚(12mmol,1.2当量),反应体系置换3次氧气，加入20mL甲苯,密封后置于120℃加热剧烈搅拌12小时至完全反应。二氯甲烷萃取三次，无水硫酸钠或者无水硫酸镁干燥，过滤，减压浓缩有机溶剂，经硅胶柱层析纯化，得到目标化合物1.32g，产率47％。
对比例1：离子对催化剂的对比
用其他离子对催化剂代替Ph3C+[B(C6F5)4]-作为反应的催化剂，则反应效果出现不同程度的下降，甚至失去催化效果。
对比例2：离子对催化剂的用量对比
降低催化剂的用量，目标产物的产率也开始相应的降低。
对比例3：反应溶剂的对比
其他溶剂替代甲苯作为反应溶剂，目标产物的产率均出现不同程度的下降甚至使得催化剂失去催化活性。
对比例4：其他反应条件的对比
气体氛围的对比显示，氧气是必须的反应物；另外随着反应温度的降低，则不利于目标产物的生成。
Claims (1)
1.一种β-咔啉类化合物的制备方法，其特征在于，该方法包括以下反应中的任意一种：
β-咔啉类化合物的制备方法：取25mL Schlenk管，配置合适大小的搅拌磁子，依次精确称量Ph3C+[B(C6F5)4]-36.8mg，色胺化合物0.2mmol,4-乙烯基苯甲醛化合物0.3mmol,反应体系置换氧气3次，加入甲苯1mL,密封后置于120℃加热剧烈搅拌12小时至完全反应；二氯甲烷萃取三次，无水硫酸钠或者无水硫酸镁干燥，过滤，减压浓缩有机溶剂，经硅胶柱层析纯化，得到目标化合物41.8mg，产率81％；
β-咔啉类化合物的制备方法：取25mL Schlenk管，配置合适大小的搅拌磁子，依次精确称量Ph3C+[B(C6F5)4]-36.8mg，色胺化合物0.2mmol,4-炔基苯甲醛化合物0.3mmol,反应体系置换氧气3次，加入甲苯1mL,密封后置于120℃加热剧烈搅拌12小时至完全反应；二氯甲烷萃取三次，无水硫酸钠或者无水硫酸镁干燥，过滤，减压浓缩有机溶剂，经硅胶柱层析纯化，得到目标化合物40.8mg，产率76％；
β-咔啉类化合物的制备方法：取25mL Schlenk管，配置合适大小的搅拌磁子，依次精确称量Ph3C+[B(C6F5)4]-36.8mg，色胺化合物0.2mmol,吲哚-3-甲醛化合物0.3mmol,反应体系置换氧气3次，加入甲苯1mL,密封后置于120℃加热剧烈搅拌12小时至完全反应；二氯甲烷萃取三次，无水硫酸钠或者无水硫酸镁干燥，过滤，减压浓缩有机溶剂，经硅胶柱层析纯化，得到目标化合物23.8mg，产率42％；(4)
β-咔啉类化合物的制备方法：取25mL Schlenk管，配置合适大小的搅拌磁子，依次精确称量Ph3C+[B(C6F5)4]-36.8mg，色胺化合物0.2mmol,丙叉保护的葡萄糖类衍生物0.3mmol,反应体系置换氧气3次，加入甲苯1mL,密封后置于120℃加热剧烈搅拌12小时至完全反应；二氯甲烷萃取三次，无水硫酸钠或者无水硫酸镁干燥，过滤，减压浓缩有机溶剂，经硅胶柱层析纯化，得到目标化合物82.6mg，产率78％；
(5)
β-咔啉类化合物的制备方法：取25mL Schlenk管，配置合适大小的搅拌磁子，依次精确称量Ph3C+[B(C6F5)4]-36.8mg，色胺化合物0.2mmol,苄基保护的豆腐果甙0.3mmol,反应体系置换氧气3次，加入甲苯1mL,密封后置于120℃加热剧烈搅拌12小时至完全反应；二氯甲烷萃取三次，无水硫酸钠或者无水硫酸镁干燥，过滤，减压浓缩有机溶剂，经硅胶柱层析纯化，得到目标化合物104.2mg，产率73％；
(6)
β-咔啉类化合物的制备方法：取25mL Schlenk管，配置合适大小的搅拌磁子，依次精确称量Ph3C+[B(C6F5)4]-36.8mg，色胺化合物0.2mmol,阿达帕林衍生物0.3mmol,反应体系置换氧气3次，加入甲苯1mL,密封后置于120℃加热剧烈搅拌12小时至完全反应；二氯甲烷萃取三次，无水硫酸钠或者无水硫酸镁干燥，过滤，减压浓缩有机溶剂，经硅胶柱层析纯化，得到目标化合物69.4mg，产率65％；
(7)
β-咔啉类化合物的制备方法：取25mL Schlenk管，配置合适大小的搅拌磁子，依次精确称量Ph3C+[B(C6F5)4]-36.8mg，色胺化合物0.2mmol,薄荷醇衍生物0.3mmol,反应体系置换氧气3次，加入甲苯1mL,密封后置于120℃加热剧烈搅拌12小时至完全反应；二氯甲烷萃取三次，无水硫酸钠或者无水硫酸镁干燥，过滤，减压浓缩有机溶剂，经硅胶柱层析纯化，得到目标化合物67.4mg，产率79％；(8)
β-咔啉类化合物的制备方法：取25mL Schlenk管，配置合适大小的搅拌磁子，依次精确称量Ph3C+[B(C6F5)4]-36.8mg，色胺化合物0.2mmol,β-紫罗兰醇衍生物0.3mmol,反应体系置换氧气3次，加入甲苯1mL,密封后置于120℃加热剧烈搅拌12小时至完全反应；二氯甲烷萃取三次，无水硫酸钠或者无水硫酸镁干燥，过滤，减压浓缩有机溶剂，经硅胶柱层析纯化，得到目标化合物59.4mg，产率70％；
(9)
β-咔啉类化合物的制备方法：取25mL Schlenk管，配置合适大小的搅拌磁子，依次精确称量Ph3C+[B(C6F5)4]-36.8mg，色胺化合物0.2mmol,二氢胆固醇衍生物0.3mmol,反应体系置换氧气3次，加入甲苯1mL,密封后置于120℃加热剧烈搅拌12小时至完全反应；二氯甲烷萃取三次，无水硫酸钠或者无水硫酸镁干燥，过滤，减压浓缩有机溶剂，经硅胶柱层析纯化，得到目标化合物61.8mg，产率47％；
(10)
化合物19的克级规模制备方法：取100mL圆底反应瓶，配置合适大小的搅拌磁子，依次精确称量Ph3C+[B(C6F5)4]-(184mg,20mol％)，色胺(1.60g,10mmol,1.0当量),对炔基苯甲醛(12mmol,1.2当量),反应体系置换3次氧气，加入20mL甲苯,密封后置于120℃加热剧烈搅拌12小时至完全反应；二氯甲烷萃取三次，无水硫酸钠或者无水硫酸镁干燥，过滤，减压浓缩有机溶剂，经硅胶柱层析纯化，得到目标化合物1.24g，产率46％；
(11)
化合物22(Eudistomin U)的克级规模制备方法：取100mL圆底反应瓶，配置合适大小的搅拌磁子，依次精确称量Ph3C+[B(C6F5)4]-(184mg,20mol％)，色胺(1.60g,10mmol,1.0当量),3-甲酰基吲哚(12mmol,1.2当量),反应体系置换3次氧气，加入20mL甲苯,密封后置于120℃加热剧烈搅拌12小时至完全反应；二氯甲烷萃取三次，无水硫酸钠或者无水硫酸镁干燥，过滤，减压浓缩有机溶剂，经硅胶柱层析纯化，得到目标化合物1.32g，产率47％。
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