5-氯-2-氯烟酸乙酯 | 148065-10-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 中文名称: 5-氯-2-氯烟酸乙酯
• 中文别名: 2,5-二氯烟酸乙酯
• 英文名称: ethyl 2,5-dichloronicotinate
• 英文别名: ethyl 2,5-dichloropyridine-3-carboxylate
• CAS: 148065-10-5
• 化学式: C₈H₇Cl₂NO₂
• mdl: MFCD07636850
• 分子量: 220.055
• InChiKey: WNYVXIWPEGGUKG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  39.2
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2933399090
• 储存条件：
  室温

反应信息

• 作为反应物：
  描述：

  5-氯-2-氯烟酸乙酯 在 四(三苯基膦)钯 、 sodium hydride 、 sodium carbonate 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 甲醇 、 乙二醇二甲醚 、 乙醇 、 二氯甲烷 、 水 、 mineral oil 为溶剂， 反应 4.25h， 生成 methyl 4-(5-chlorothieno[2,3-b]pyridin-3-yl)-2-cyclopentylbenzoate
  参考文献：
  名称：

  Hinge Binder Scaffold Hopping Identifies Potent Calcium/Calmodulin-Dependent Protein Kinase Kinase 2 (CAMKK2) Inhibitor Chemotypes

  摘要：

  DOI：

  10.1021/acs.jmedchem.0c02274
• 作为产物：
  描述：

  在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 5.0h， 以82%的产率得到5-氯-2-氯烟酸乙酯
  参考文献：
  名称：

  A modified approach to C-14-labeled 2-(3,4-difluorophenoxy)-5-fluoronicotinic acid and other halogen-substituted analogs

  摘要：

  基于1,4,4-三取代丁二烯的电环合闭环反应，开发了一种改良的碳-14标记吡啶环系方法。该新方法应用于制备2-(3,4-二氟苯氧基)-5-氟-[2-14C]尼古丁酸及其他卤素取代的类似物。从乙基[1-14C]氰基乙酸酯出发，经过四步放射化学步骤，总放射化学产率为39%，分离得到了目标化合物，其放射化学纯度>98%，比活度为53 mCi/mmol。版权所有 © 2011 John Wiley & Sons, Ltd。

  DOI：

  10.1002/jlcr.1887

文献信息

• [EN] SUBSTITUTED METHYL ARYL OR HETEROARYL AMIDE COMPOUNDS<br/>[FR] COMPOSES METHYLARYL- OU HETEROARYLAMIDES SUBSTITUES
  申请人：PFIZER JAPAN INC

  公开号：WO2005105732A1

  公开（公告）日：2005-11-10

  This invention provides a compound of the formula (I), wherein X represents a carbon atom or the like: Y represents imino, or the like: R1 represents an alkyl group having from 1 to 6 carbon atoms or the like: R2 and R3 independently represents a hydrogen atom or the like. These compounds are useful for the treatment of disease conditions mediated by prostaglandin such as pain, or the like in mammalian. This invention also provides a pharmaceutical composition comprising the above compound.

  本发明提供了一种化合物，其化学式为（I），其中X代表碳原子或类似物：Y代表亚胺基或类似物：R1代表具有1至6个碳原子的烷基基团或类似物：R2和R3独立地代表氢原子或类似物。这些化合物对于治疗由前列腺素介导的疾病状况，如哺乳动物中的疼痛等，具有用处。本发明还提供了包括上述化合物的药物组合物。
• Concise, gram-scale synthesis of furo[2,3-b]pyridines with functional handles for chemoselective cross-coupling
  作者：Sean N. O'Byrne、Benjamin J. Eduful、Timothy M. Willson、David H. Drewry

  DOI：10.1016/j.tetlet.2020.152353

  日期：2020.9

  A concise 4-step synthesis of furo[2,3-b]pyridines, with handles in the 3- and 5-positions for palladium mediated cross-coupling reactions, is described. The synthetic route has been optimized, with only one step requiring purification by column chromatography. The route is amenable to scale-up, and was successfully executed on a multi-gram scale. Furopyridines are of growing interest in medicinal

  描述了呋喃并[2,3- b ]吡啶的简明四步合成，在 3 位和 5 位上有用于钯介导的交叉偶联反应的手柄。合成路线经过优化，仅一步需要柱层析纯化。该路线适合按比例放大，并已在数克规模上成功实施。呋喃并吡啶在药物化学中越来越受到关注，这种途径应该能够轻松获得构效关系 (SAR) 研究的核心。
• Substituted methyl aryl or heteroaryl amide compounds
  申请人：Koike Hiroki

  公开号：US20050267170A1

  公开（公告）日：2005-12-01

  This invention provides a compound of the formula (I): wherein X represents a carbon atom or the like: Y represents imino, or the like: R 1 represents an alkyl group having from 1 to 6 carbon atoms or the like: R 2 and R 3 independently represents a hydrogen atom or the like. These compounds are useful for the treatment of disease conditions mediated by prostaglandin such as pain, or the like in mammalian. This invention also provides a pharmaceutical composition comprising the above compound.

  本发明提供了公式(I)的化合物：其中X代表碳原子或类似物；Y代表亚氨基或类似物；R1代表1至6个碳原子的烷基或类似物；R2和R3独立地代表氢原子或类似物。这些化合物对于治疗由前列腺素介导的疾病状况，如哺乳动物中的疼痛等，非常有用。本发明还提供了包含上述化合物的制药组合物。
• Nicotinamide acids, amides, and their mimetics active as inhibitors of PDE4 isozymes
  申请人：Pfizer Inc.

  公开号：US20020111495A1

  公开（公告）日：2002-08-15

  Compounds useful as inhibitors of PDE4 in the treatment of diseases regulated by the activation and degranulation of eosinophils, especially asthma, chronic bronchitis, and chronic obstructuive pulmonary disease, of the formula: 1 wherein j is 0 or 1, k is 0 or 1, m is 0, 1, or 2; n is 1 or 2; A is selected from the partial Formulas: 2 where q is 1, 2, or 3, W 3 is —O—; —N(R 9 )—; or —OC(═O)—; R 7 is selected from —H; —(C 1 -C 6 ) alkyl, —(C 2 -C 6 ) alkenyl, or —(C 2 -C 6 ) alkynyl substituted by 0 to 3 substituents R 10 ; —(CH 2 ) u —(C 3 -C 7 ) cycloalkyl where u is 0, 1 or 2, substituted by 0 to 3 R 10 ; and phenyl or benzyl substituted by 0 to 3 R 14 ; R 8 is tetrazol-5-yl; 1,2,4-triazol-3-yl; 1,2,4-triazol-3-on-5-yl; 1,2,3-triazol-5-yl; imidazol-2-yl; imidazol-4-yl; imidazolidin-2-on-4-yl; 1,3,4-oxadiazolyl; 1,3,4-oxadiazol-2-on-5-yl; 1,2,4-oxadiazol-3-yl; 1,2,4-oxadiazol-5-on-3-yl; 1,2,4-oxadiazol-5-yl; 1,2,4-oxadiazol-3-on-5-yl; 1,2,5-thiadiazolyl; 1,3,4-thiadiazolyl; morpholinyl; parathiazinyl; oxazolyl; isoxazolyl; thiazolyl; isothiazolyl; pyrrolyl; pyrazolyl; succinimidyl; glutarimidyl; pyrrolidonyl; 2-piperidonyl; 2-pyridonyl; 4-pyridonyl; pyridazin-3-onyl; pyridyl; pyrimidinyl; pyrazinyl; pyridazinyl; indolyl; indolinyl; isoindolinyl; benzo[b]furanyl; 2,3-dihydrobenzofuranyl; 1,3-dihydroisobenzofuranyl; 2H-1-benzopyranyl; 2-H-chromenyl; chromanyl; benzothienyl; 1H-indazolyl; benzimidazolyl; benzoxazolyl; benzisoxazolyl; benzothiazolyl; benzotriazolyl; benzotriazinyl; phthalazinyl; 1,8-naphthyridinyl; quinolinyl; isoquinolinyl; quinazolinyl; quinoxalinyl; pyrazolo[3,4-d]pyrimidinyl; pyrimido[4,5-d]pyrimidinyl; imidazo[1,2-a]pyridinyl; pyridopyridinyl; pteridinyl; or 1H-purinyl; or A is selected from phosphorous and sulfur acid groups; W is —O—; —S(═O) t —, where t is 0, 1, or 2; or —N(R 3 )—; Y is ═C(R 1 a )—, or —[N (O) k ] where k is 0 or 1; R 4 , R 5 and R 6 are (1) —H; provided that R 5 and R 6 are not both —H at the same time, —F; —Cl; —(C 2 -C 4 ) alkynyl; —R 16 ; —OR 16 ; —S(═O) p R 16 ; —C(═O)R 16 , —C(═O)OR 16 , —C(═O)OR 16 ; —OC(═O)R 16 ; —CN; —NO 2 ; —C(═O)NR 16 R 17 ; —OC(═O)NR 16 R 17 ; —NR 12 a C(═O)NR 16 R 17 ; —NR 12 a C(═NR 12 )NR 16 R 17 ; —NR 12 a C(═NCN)NR 16 R 16 ; —NR 12 a C(═N—NO 2 )NR 15 R 16 ; —C(═NR 12 a )NR 15 R 16 ; —CH 2 C(═NR 12 a )NR 16 R 17 ; —OC(═NR 12 a )NR 16 R 17 ; —OC(═N—NO 2 )NR 16 R 17 ; —NR 16 R 17 ; —CH 2 NR 16 R 17 ; —NR 12 a C(═O)R 16 ; —NR 12 a C(═O)OR 16 ; ═NOR 16 ; —NR 12 a S(═O) p R 17 —S(═O) p NR 16 R 17 ; and —CH 2 C(═NR 12 a )NR 16 R 17 ; (2) —(C 1 -C 4 ) alkyl including dimethyl and —(C 1 -C 4 ) alkoxy substituted with 0 to 3 substituents —F or —Cl; or 0 or 1 substituent (C 1 -C 2 ) alkoxycarbonyl-, (C 1 -C 2 ) alkylcarbonyl-, or (C 1 -C 2 ) alkylcarbonyloxy-; or (3) an aryl or heterocyclic moiety; or (4) R 5 and R 6 are taken together to form a moiety of partial Formulas (1.3.1) through (1.3.15): 3 or a pharmaceutically acceptable salt thereof.

  本发明涉及一种化合物，其在治疗由嗜酸性粒细胞活化和脱颗粒调节的疾病中，特别是哮喘、慢性支气管炎和慢性阻塞性肺疾病中作为PDE4抑制剂有用，其化学式为：其中j为0或1，k为0或1，m为0、1或2；n为1或2；A从部分式中选取：其中q为1、2或3，W3为—O—；—N(R9)—；或—OC(═O)—；R7选自—H；—(C1-C6)烷基、—(C2-C6)烯基或—(C2-C6)炔基，其上可有0至3个取代基R10；—(CH2)u—(C3-C7)环烷基，其中u为0、1或2，其上可有0至3个取代基R10；以及苯基或苄基，其上可有0至3个取代基R14；R8为四唑-5-基；1,2,4-三唑-3-基；1,2,4-三唑-3-酮-5-基；1,2,3-三唑-5-基；咪唑-2-基；咪唑-4-基；咪唑啉-2-酮-4-基；1,3,4-噁二唑基；1,3,4-噁二唑-2-酮-5-基；1,2,4-噁二唑-3-基；1,2,4-噁二唑-5-酮-3-基；1,2,4-噁二唑-5-基；1,2,4-噁二唑-3-酮-5-基；1,2,5-噻二唑基；1,3,4-噻二唑基；吗啉基；对噻嗪基；噁唑基；异噁唑基；噻唑基；异噻唑基；吡咯基；吡唑基；琥珀酰亚胺基；戊二酰亚胺基；吡咯烷基；2-哌啶酮基；2-吡啶酮基；4-吡啶酮基；吡啶嗪-3-酮基；吡啶基；嘧啶基；吡嗪基；吡啶嗪基；吲哚基；吲哚啉基；异吲哚啉基；苯并[b]呋喃基；2,3-二氢苯并呋喃基；1,3-二氢异苯并呋喃基；2H-1-苯并吡喃基；2-H-香豆素基；香豆素基；苯并噻吩基；1H-吲唑基；苯并咪唑基；苯并噁唑基；苯并异噁唑基；苯并噻唑基；苯并三唑基；苯并三唑啉基；邻苯二酚基；1,8-萘啶基；喹啉基；异喹啉基；喹唑啉基；喹啉酮基；吡唑并[3,4-d]嘧啶基；嘧啶并[4,5-d]嘧啶基；咪唑并[1,2-a]吡啶基；吡啶吡啶基；噻吩基；或1H-嘌呤基；或A选自磷和硫酸基；W为—O—；—S(═O)t—，其中t为0、1或2；或—N(R3)—；Y为═C(R1a)—，或—[N(O)k]，其中k为0或1；R4、R5和R6为(1) —H；但是当R5和R6同时不为—H时，可以为—F；—Cl；—(C2-C4)炔基；—R16；—OR16；—S(═O)pR16；—C(═O)R16、—C(═O)OR16、—C(═O)OR16；—OC(═O)R16；—CN；—NO2；—C(═O)NR16R17；—OC(═O)NR16R17；—NR12aC(═O)NR16R17；—NR12aC(═NR12)NR16R17；—NR12aC(═NCN)NR16R16；—NR12aC(═N—NO2)NR15R16；—C(═NR12a)NR15R16；—CH2C(═NR12a)NR16R17；—OC(═NR12a)NR16R17；—OC(═N—NO2)NR16R17；—NR16R17；—CH2NR16R17；—NR12aC(═O)R16；—NR12aC(═O)OR16；═NOR16；—NR12aS(═O)pR17—S(═O)pNR16R17；和—CH2C(═NR12a)NR16R17；(2) —(C1-C4)烷基，包括二甲基和—(C1-C4)烷氧基，其上可有0至3个取代基—F或—Cl；或者0或1个取代基(C1-C2)烷氧羰基、(C1-C2)烷基羰基或(C1-C2)烷基羰氧基；或者(3) 芳基或杂环基；或者(4) R5和R6聚合形成部分式(1.3.1)到(1.3.15)中的一个基团；或其药学上可接受的盐。
• Combinations Comprising Alpha-2-Delta Ligands and Ep4 Receptor Antagonists
  申请人：Audoly Laurent Pascal

  公开号：US20090036495A1

  公开（公告）日：2009-02-05

  The instant invention relates to a combination of an EP4-receptor antagonist and an alpha-2-delta ligand, and pharmaceutically acceptable salts thereof, pharmaceutical compositions thereof and their use in the treatment of pain, particularly inflammatory, neuropathic, visceral and nociceptive pain.

  本发明涉及一种EP4受体拮抗剂和α-2-δ配体的组合物，及其药学上可接受的盐、制药组合物及其在治疗疼痛，特别是炎症性、神经病理性、内脏性和伤害性疼痛中的用途。