CN114874187A - 维他昔布的制备方法 - Google Patents
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- NSWKPXFHCORWAE-UHFFFAOYSA-N 2-[4-chloro-5-(4-methylphenyl)imidazol-1-yl]-5-methylsulfonylpyridine Chemical compound C1=CC(C)=CC=C1C1=C(Cl)N=CN1C1=CC=C(S(C)(=O)=O)C=N1 NSWKPXFHCORWAE-UHFFFAOYSA-N 0.000 title abstract description 14
- 238000002360 preparation method Methods 0.000 title abstract description 11
- KAXMCTQJURUBDH-UHFFFAOYSA-N 2-[5-(4-methylphenyl)imidazol-1-yl]-5-methylsulfonylpyridine Chemical compound C1=CC(C)=CC=C1C1=CN=CN1C1=CC=C(S(C)(=O)=O)C=N1 KAXMCTQJURUBDH-UHFFFAOYSA-N 0.000 claims abstract description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims abstract description 12
- -1 5- (methylsulfonyl) pyridine-2-yl Chemical group 0.000 claims abstract description 10
- YDVCUSJBYYFJPM-UHFFFAOYSA-N 5-methylsulfonylpyridin-2-amine Chemical compound CS(=O)(=O)C1=CC=C(N)N=C1 YDVCUSJBYYFJPM-UHFFFAOYSA-N 0.000 claims abstract description 8
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims abstract description 8
- 238000000034 method Methods 0.000 claims abstract description 7
- FXLOVSHXALFLKQ-UHFFFAOYSA-N p-tolualdehyde Chemical compound CC1=CC=C(C=O)C=C1 FXLOVSHXALFLKQ-UHFFFAOYSA-N 0.000 claims abstract description 6
- CFOAUYCPAUGDFF-UHFFFAOYSA-N tosmic Chemical compound CC1=CC=C(S(=O)(=O)C[N+]#[C-])C=C1 CFOAUYCPAUGDFF-UHFFFAOYSA-N 0.000 claims abstract description 4
- 238000006243 chemical reaction Methods 0.000 claims description 21
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 2
- 150000002466 imines Chemical class 0.000 abstract description 4
- 229960002004 valdecoxib Drugs 0.000 abstract description 3
- LNPDTQAFDNKSHK-UHFFFAOYSA-N valdecoxib Chemical compound CC=1ON=C(C=2C=CC=CC=2)C=1C1=CC=C(S(N)(=O)=O)C=C1 LNPDTQAFDNKSHK-UHFFFAOYSA-N 0.000 abstract description 3
- 239000007858 starting material Substances 0.000 abstract description 2
- HGTYMLFMXKYIQW-ZETCQYMHSA-N (4s)-5,7-difluoro-3,4-dihydro-2h-chromen-4-ol Chemical compound FC1=CC(F)=C2[C@@H](O)CCOC2=C1 HGTYMLFMXKYIQW-ZETCQYMHSA-N 0.000 abstract 2
- 239000003513 alkali Substances 0.000 abstract 1
- 239000012069 chiral reagent Substances 0.000 abstract 1
- 238000005984 hydrogenation reaction Methods 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- 239000003814 drug Substances 0.000 description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 102000010907 Cyclooxygenase 2 Human genes 0.000 description 5
- 108010037462 Cyclooxygenase 2 Proteins 0.000 description 5
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- WGOLHUGPTDEKCF-UHFFFAOYSA-N 5-bromopyridin-2-amine Chemical compound NC1=CC=C(Br)C=N1 WGOLHUGPTDEKCF-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 4
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- 239000000543 intermediate Substances 0.000 description 4
- 238000005070 sampling Methods 0.000 description 4
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- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 3
- 241000282326 Felis catus Species 0.000 description 3
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 3
- 229930182821 L-proline Natural products 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 229960002429 proline Drugs 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- KKVTYAVXTDIPAP-UHFFFAOYSA-M sodium;methanesulfonate Chemical compound [Na+].CS([O-])(=O)=O KKVTYAVXTDIPAP-UHFFFAOYSA-M 0.000 description 3
- 150000003568 thioethers Chemical class 0.000 description 3
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 229940111134 coxibs Drugs 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 150000002978 peroxides Chemical class 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- RMBAVIFYHOYIFM-UHFFFAOYSA-M sodium methanethiolate Chemical compound [Na+].[S-]C RMBAVIFYHOYIFM-UHFFFAOYSA-M 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- PAJALBWYDSQWAV-UHFFFAOYSA-N 1-isocyanosulfonyl-4-methylbenzene Chemical compound CC1=CC=C(S(=O)(=O)[N+]#[C-])C=C1 PAJALBWYDSQWAV-UHFFFAOYSA-N 0.000 description 1
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
- YUBHMOQVHOODEI-UHFFFAOYSA-N 5-chloro-2-nitropyridine Chemical compound [O-][N+](=O)C1=CC=C(Cl)C=N1 YUBHMOQVHOODEI-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 229940124639 Selective inhibitor Drugs 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 230000001760 anti-analgesic effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 239000003255 cyclooxygenase 2 inhibitor Substances 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 231100001261 hazardous Toxicity 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000013341 scale-up Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 238000009987 spinning Methods 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
Classifications
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- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Rheumatology (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pain & Pain Management (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pyridine Compounds (AREA)
Abstract
本发明涉及一条维他昔布的制备方法,关键步骤为：5‑(甲磺酰基)吡啶‑2‑胺在乙酸作用下与对甲基苯甲醛反应，制备得到N‑(5‑(甲磺酰基)吡啶‑2‑基)‑1‑(对甲苯基)甲亚胺；该亚胺化合物在碱的作用下和对甲基苯磺酰甲基异腈(TosMIC)反应制备得到5‑(甲磺酰基)‑2‑(5‑(对甲苯基)‑1H‑咪唑‑1‑基)吡啶；最后，5‑(甲磺酰基)‑2‑(5‑(对甲苯基)‑1H‑咪唑‑1‑基)吡啶使用NCS进行氯化得到维他昔布。具体涉及(S)‑5,7‑二氟‑3,4‑二氢‑2H‑色原烯‑4‑醇的制备方法。该方法以5,7‑二氟‑4H‑苯并吡喃‑4‑酮为起始物料，通过手性试剂对酮羰基的不对称还原和随后的常规氢化反应，实现(S)‑5,7‑二氟‑3,4‑二氢‑2H‑色原烯‑4‑醇的制备。
Description
技术领域
本发明涉及药物化学领域，具体涉及一条维他昔布的制备方法。
背景技术
维他昔布是一种新型非甾体类抗炎药，在水中溶解度小，表现为亲脂性，是环氧化酶-2(COX-2)的高选择性抑制剂，可特异性抑制环氧化酶-2的生成，从而减少炎性前列腺素类物质的合成与集聚，达到抗炎、镇痛和退热作用。该药物的最大创新点在于根据酶晶体结构研究，创造性地在分子特定位置引入N原子，通过药物分子与COX-2之间的氢键作用，提高了药物分子对COX-2的抑制作用和选择性，成为该类药中第一个实现在犬、猫和马中都具有高选择性的COX-2抑制剂。在动物试验中，该药对犬和猫均具有优异的抗炎镇痛效果，同时表现出优于同类产品的安全性，该药已经成为国内唯一猫用高COX-2选择性抑制剂。
CN102464652报道了一种维他昔布的合成路线。该路线以5-氯-2-硝基吡啶为起始物料，先对一侧卤素使用甲硫醇钠进行甲硫基化，再对另一侧的硝基使用铁粉还原成氨基；得到的化合物与对甲基苯甲醛反应，得到亚胺中间体，亚胺中间体再在碱性试剂的作用下和TosMIC发生反应成咪唑环，得到5-(甲基巯基)-2-(5-(对甲苯基)-1H-咪唑-1-基)吡啶，5-(甲基巯基)-2-(5-(对甲苯基)-1H-咪唑-1-基)吡啶在间氯过氧苯甲酸作用下对甲硫基进行氧化得到5-(甲磺酰基)-2-(5-(对甲苯基)-1H-咪唑-1-基)吡啶；最后在氯代试剂NCS的作用下，对5-(甲磺酰基)-2-(5-(对甲苯基)-1H-咪唑-1-基)吡啶进行氯化得到维他昔布。该路线较为冗长，存在如下缺陷：1)甲硫醇钠臭味大，大量使用时对环境会造成大的影响；2)涉及到的4个中间体都为硫醚化合物，臭味大；3)氧化硫醚过程中涉及到使用过氧化物，具有危险性；4)反应路线冗长，收率较低。相关合成路线如下：
因此，开发新的合成维他昔布的方法，以获得具有操作简便、易于实施、成本低、环境友好以及适用于工业放大生产的工艺具有重要的意义。
发明内容
针对上述维他昔布的制备方法，其存在反应路线长，涉及危险试剂或危险反应，不环保的问题，本发明是提供一种维他昔布的制备方法，该方法具有反应条件温和、成本低廉，不涉及危险试剂和危险反应的特点。
研究发现，5-溴-2-氨基吡啶在L-脯氨酸/CuI存在下与甲基磺酸钠反应，制备得到得到5-(甲磺酰基)吡啶-2-胺。5-(甲磺酰基)吡啶-2-胺在乙酸作用下与对甲基苯甲醛反应，制备得到N-(5-(甲磺酰基)吡啶-2-基)-1-(对甲苯基)甲亚胺。N-(5-(甲磺酰基)吡啶-2-基)-1-(对甲苯基)甲亚胺不经后处理，直接进行下一步反应，在碱的作用下和对甲基苯磺酰甲基异腈(TosMIC)反应制备得到5-(甲磺酰基)-2-(5-(对甲苯基)-1H-咪唑-1-基)吡啶。最后，5-(甲磺酰基)-2-(5-(对甲苯基)-1H-咪唑-1-基)吡啶使用NCS进行氯化得到维他昔布。具体反应路线如下：
化合物5-溴-2-氨基吡啶在L-脯氨酸/CuI存在下和甲磺酸钠反应制备得到化合物5-(甲磺酰基)吡啶-2-胺，所述反应的溶剂为DMSO，反应温度为120-130℃之间。
化合物5-(甲磺酰基)吡啶-2-胺和对甲基苯甲醛反应制备得到化合物N-(5-(甲磺酰基)吡啶-2-基)-1-(对甲苯基)甲亚胺，反应的溶剂为甲苯，反应温度为溶剂的回流温度。
化合物N-(5-(甲磺酰基)吡啶-2-基)-1-(对甲苯基)甲亚胺和对甲基苯磺酰甲基异腈(TosMIC)在K2CO3存在下反应制备得到化合物5-(甲磺酰基)-2-(5-(对甲苯基)-1H-咪唑-1-基)吡啶，反应的溶剂为乙二醇二甲醚/甲醇。
化合物5-(甲磺酰基)-2-(5-(对甲苯基)-1H-咪唑-1-基)吡啶使用NCS进行氯化，制备得到维他昔布，反应的溶剂为DMF。
本发明提供的制备维他昔布的方法，从5-溴-2-氨基吡啶出发，仅需4步反应，反应过程不涉及使用硫醚类臭味大的起始物料和中间体，同时不涉及使用危险性高的过氧化物，对于维他昔布的产业化生产具有重要的意义。
具体实施方式
为了使本领域的技术人员更好地理解本发明的技术方案，下面进一步披露一些非限制实施例，对本发明作进一步的详细说明。
实施例1：5-(甲磺酰基)吡啶-2-胺的制备
在100mL单口瓶中加入化合物5-溴-2-氨基吡啶(10g，57.8mmol)，甲基磺酸钠(8.85g，74.95mmol)，L-脯氨酸(1.33g，11.5mmol)和碘化亚铜(2.2g，11.5mmol)，加入DMSO(50mL)，氮气保护下控温123±3℃，反应过夜。取样测试，原料反应完毕。体系降温至室温，加入水(100mL)和二氯甲烷(100mL)，搅拌分液；水相用二氯甲烷(50mL)萃洗一次，合并有机相。有机相用15％氨水(30mL)洗一次，再用水洗涤3次(3×50mL)，得到有机相。有机相旋干，过硅胶柱(纯二氯甲烷)，得到8.96g类黄色固体。收率90.0％。1H NMR(600MHz,DMSO)δ8.35(s,1H),7.75(d,J＝8.6Hz,1H),6.97(s,2H),6.52(d,J＝8.7Hz,1H),3.11(s,3H)。
实施例2：化合物5-(甲磺酰基)-2-(5-(对甲苯基)-1H-咪唑-1-基)吡啶的制备
在250mL单口瓶中加入化合物5-(甲磺酰基)吡啶-2-胺(10g，58.1mmol)，对甲基苯甲醛(6.3g，52.5mmol)，乙酸(1.5g，25.0mmol)和甲苯(40mL)，氮气保护下回流分水20h。取样测试，原料反应完毕。体系控温50-60℃旋干溶剂，得到约18g固体(N-(5-(甲磺酰基)吡啶-2-基)-1-(对甲苯基)甲亚胺粗品，不用纯化，直接用于下一步反应)。所得固体置于反应瓶中加入碳酸钾(16.2g，117.2mmol)，对甲苯磺酰基异腈(19.5g，99.88mmol)，乙二醇二甲醚(90mL)和甲醇(60mL)，控温75℃，搅拌16h。取样测试，(N-(5-(甲磺酰基)吡啶-2-基)-1-(对甲苯基)甲亚胺反应完毕。体系控温40-50℃，脱溶至干，加入乙酸乙酯(90mL)和水(90mL)，萃取分液，有机相用饱和食盐水(45mL)洗一次，得到的有机相旋干，得到固体，固体用乙酸乙酯重结晶一次，得到化合物5-(甲磺酰基)-2-(5-(对甲苯基)-1H-咪唑-1-基)吡啶，为类白色固体：15.4g，收率：84.6％。1H NMR(600MHz,CDCl3)δ9.05(s,1H),8.28(d,J＝17.2Hz,1H),8.08(d,J＝8.5Hz,1H),7.20(d,J＝4.3Hz,3H),7.13(d,J＝7.8Hz,2H),6.93(d,J＝8.5Hz,1H),3.14(s,3H),2.40(s,3H)。
实施例3：维他昔布的制备
在单口瓶中，加入化合物5-(甲磺酰基)-2-(5-(对甲苯基)-1H-咪唑-1-基)吡啶(12g，38.3mmol)和DMF(50mL)，控温105℃。向反应体系中滴加NCS(5.28g，39.5mmol)的DMF(100mL)溶液。滴加完毕后，体系搅拌12h。取样测试，原料反应完毕。体系自然降温后加水(150mL)搅拌，抽滤，得到维他昔布固体：10.1g。收率：75.8％。1H NMR(600MHz,CDCl3)δ9.03(d,J＝1.7Hz,1H),8.25(s,1H),8.06(dd,J＝8.5,2.2Hz,1H),7.25(d,J＝7.7Hz,2H),7.18(d,J＝7.9Hz,2H),6.83(d,J＝8.5Hz,1H),3.13(s,3H),2.42(s,3H)。
Claims (1)
1.制备5-(甲磺酰基)-2-(5-(对甲苯基)-1H-咪唑-1-基)吡啶的方法，具体为：5-(甲磺酰基)吡啶-2-胺在乙酸作用下与对甲基苯甲醛反应，制备得到N-(5-(甲磺酰基)吡啶-2-基)-1-(对甲苯基)甲亚胺，N-(5-(甲磺酰基)吡啶-2-基)-1-(对甲苯基)甲亚胺在碳酸钾的作用下和对甲基苯磺酰甲基异腈(TosMIC)反应，制备得到5-(甲磺酰基)-2-(5-(对甲苯基)-1H-咪唑-1-基)吡啶。反应式如下：
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