3,5-bis(ethoxycarbonyl)-4-hydroxy-1H-pyrazole | 23705-86-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3,5-bis(ethoxycarbonyl)-4-hydroxy-1H-pyrazole
• 英文别名: 3,5-Bis-ethoxycarbonyl-4-hydroxypyrazol, 4-Hydroxy-pyrazol-3,5-dicarbonsaeureethylester；3,5-Dicarbethoxy-pyrazol-4-ol；3,5-Bis-ethoxycarbonyl-4-hydroxypyrazol；3,5-Dicarbethoxy-4-hydroxy-pyrazol；4-hydroxy-1H-pyrazole-3,5-dicarboxylic acid diethyl ester；4-Hydroxy-1H-pyrazol-3,5-dicarbonsaeure-diaethylester；3,5-Di-(ethoxycarbonyl)-4-hydroxy-pyrazol；3,5-Dicarboethoxy-4-hydroxypyrazole；diethyl4-hydroxy-1H-pyrazole-3,5-dicarboxylate；diethyl 4-hydroxy-1H-pyrazole-3,5-dicarboxylate
• CAS: 23705-86-4
• 化学式: C₉H₁₂N₂O₅
• 分子量: 228.205
• InChiKey: FYDAPYQJPDDRCU-UHFFFAOYSA-N

物化性质

• 熔点：
  151 °C
• 沸点：
  351.8±37.0 °C(Predicted)
• 密度：
  1.356±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  16
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  102
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3,5-bis(ethoxycarbonyl)-4-hydroxy-1H-pyrazole 在 palladium on activated charcoal sodium hydroxide 、 lithium aluminium tetrahydride 、 四丁基溴化铵 、 氢气 、 三溴化磷 、 sodium hydride 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 25.0~60.0 ℃ 、344.74 kPa 条件下， 反应 71.0h， 生成 4-hydroxy-3,5-bis(2,5,8,11-tetraoxadodecan-1-yl)-1H-pyrazole
  参考文献：
  名称：

  Selective dopamine receptors: Synthesis, complexing properties, and molecular modelling studies of new podands derived from 4-hydroxy-1H-pyrazole

  摘要：

  New podands derived from 4-hydroxy-1H-pyrazole have been prepared. Their complexing properties towards cations (Na+, K+, NH4+) and some neurotransmitters (dopamine and norepinephrine) have been studied, using biphasic extraction experiments, molecular modelling, and a NMR titration. Podand 10, 1-benzyl-4-hydroxy-3,5-bis(2, 5, 8, 11-tetraoxadodecan-l-yl)-1H-pyrazole, showed an interesting selective complexation of dopamine. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4020(99)00047-2
• 作为产物：
  描述：

  1,3-丙酮二羧酸二乙酯 在 1-叠氮基-2-(三氟甲基)苯 、 乙醇 、 sodium 作用下， 反应 3.0h， 生成 3,5-bis(ethoxycarbonyl)-4-hydroxy-1H-pyrazole
  参考文献：
  名称：

  10.33224/rrch.2021.66.5.07

  摘要：

  DOI：

  10.33224/rrch.2021.66.5.07

文献信息

• PYRAZOLO[1,5-A]PYRAZIN-4-YL DERIVATIVES
  申请人：Pfizer Inc.

  公开号：US20170240552A1

  公开（公告）日：2017-08-24

  A compound compound having the structure: or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate of said compound or pharmaceutically acceptable salt, wherein A, A′ and A″ are independently O, C═O, C—R′ or N—R″, where R′ and R″ may independently be H, amino, —NR 7 COR 6 , COR 6 , —CONR 7 R 8 , C 1 -C 6 alkyl, or hydroxy(C 1 -C 6 alkyl), and R″ may be present or absent, and is present where the rules of valency permit, and where not more than one of A, A′ and A″ is O or C═O; R 0 and R are independently H, Br, Cl, F, or C 1 -C 6 alkyl; R 1 is H, C 1 -C 6 alkyl, or hydroxy(C 1 -C 6 alkyl); R 2 is selected from the group consisting of H, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, hydroxy(C 1 -C 6 alkyl), phenyl(C 1 -C 6 alkyl), formyl, heteroaryl, heterocyclic, —COR 6 , —OCOR 6 , —COOR 6 , —NR 7 COR 6 , —CONR 7 R 8 , and —(CH 2 ) n —W, where W is cyano, hydroxy, C 3 -C 8 cycloalkyl, —SO 2 NR 7 R 8 , and —SO 2 —R 9 , where R 9 is C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, heteroaryl, or heterocyclic; wherein each of said alkyl, cycloalkyl, heterocyclic, or heteroaryl may be unsubstituted or substituted by halo, cyano, hydroxy, or C 1 -C 6 alkyl; X is C—R 3 or N, where R 3 may be H or C 1 -C 6 alkyl; R 4 and R 5 are independently H, amino, C 1 -C 6 alkyl, or hydroxy(C 1 -C 6 alkyl); R 6 , R 7 and R 8 are each independently H, C 1 -C 6 alkyl, C 1 -C 4 alkoxy(C 1 -C 6 alkyl), or C 3 -C 8 cycloalkyl, said C 1 -C 6 alkyl is optionally substituted by halo, CN or hydroxy; or, R 7 and R 8 together with the atom bonded thereto form a 5- or 6-membered ring, said ring being optionally substituted by halo, hydroxy, CN, or C 1 -C 6 alkyl; and, n is 0, 1, 2 or 3. Also provided are methods of treatment as Janus Kinase inhibitors and pharmaceutical compositions containing the compounds of the invention and combinations thereof with other therapeutic agents.

  一种化合物，其结构为：或其药学上可接受的盐，或该化合物或药学上可接受的盐的药学上可接受的溶剂，其中A、A'和A"独立地为O、C═O、C—R'或N—R"，其中R'和R"可以独立地为H、氨基、—NR7COR6、COR6、—CONR7R8、C1-C6烷基或羟基（C1-C6烷基），并且R"可以存在或不存在，在价性规则允许的情况下存在，且A、A'和A"中不超过一个为O或C═O；R0和R独立地为H、Br、Cl、F或C1-C6烷基；R1为H、C1-C6烷基或羟基（C1-C6烷基）；R2选自H、C1-C6烷基、C1-C6烷氧基、羟基（C1-C6烷基）、苯基（C1-C6烷基）、甲酰基、杂环芳基、杂环、—COR6、—OCOR6、—COOR6、—NR7COR6、—CONR7R8和—（CH2）n—W的群，其中W为氰基、羟基、C3-C8环烷基、—SO2NR7R8和—SO2—R9，其中R9为C1-C6烷基、C3-C8环烷基、杂环芳基或杂环；其中所述的每个烷基、环烷基、杂环或杂环芳基可以是未取代的或被卤素、氰基、羟基或C1-C6烷基取代的；X为C—R3或N，其中R3可以为H或C1-C6烷基；R4和R5独立地为H、氨基、C1-C6烷基或羟基（C1-C6烷基）；R6、R7和R8各自独立地为H、C1-C6烷基、C1-C4烷氧（C1-C6烷基）或C3-C8环烷基，所述的C1-C6烷基可以选择性地被卤素、CN或羟基取代；或者，R7和R8与其结合的原子形成一个5-或6-成员环，该环可以选择性地被卤素、羟基、CN或C1-C6烷基取代；n为0、1、2或3。还提供了作为Janus激酶抑制剂的治疗方法以及含有该发明化合物的药物组合物和其他治疗剂的药物组合物。
• Selective .beta.3 adrenergic agonists
  申请人：Eli Lilly and Company

  公开号：US06046227A1

  公开（公告）日：2000-04-04

  The present invention is in the field of medicine, particularly in the treatment of Type II diabetes and obesity. More specifically, the present invention relates to selective .beta..sub.3 receptor agonists useful in the treatment of Type II diabetes and obesity. The invention provides compounds and methods of treating type II diabetes and obesity, comprising administering to a mammal in need thereof compounds of the Formula I:

  本发明属于医学领域，特别是在治疗2型糖尿病和肥胖方面。更具体地说，本发明涉及选择性β3受体激动剂，用于治疗2型糖尿病和肥胖。该发明提供了一种化合物和治疗2型糖尿病和肥胖的方法，包括向需要的哺乳动物施用Formula I的化合物。
• Selective &bgr;3 adrenergic agonists
  申请人：Eli Lilly and Company

  公开号：US06232337B1

  公开（公告）日：2001-05-15

  The present invention is in the field of medicine, particularly in the treatment of Type II diabetes and obesity. More specifically, the present invention relates to selective &bgr;3 receptor agonists useful in the treatment of Type II diabetes and obesity. The invention provides compounds and methods of treating Type II diabetes and obesity, comprising administering to a mammal in need thereof compounds of formula (I) or a pharmaceutically acceptable salt thereof. The variables of formula (I) have the meanings defined herein.

  本发明涉及医学领域，特别是治疗II型糖尿病和肥胖的领域。更具体地说，本发明涉及用于治疗II型糖尿病和肥胖的选择性β3受体激动剂。该发明提供了化合物和治疗II型糖尿病和肥胖的方法，包括向需要的哺乳动物给予式(I)的化合物或其药用盐。式(I)的变量在此定义。
• Quantification of the Electrophilicities of Diazoalkanes: Kinetics and Mechanism of Azo Couplings with Enamines and Sulfonium Ylides
  作者：Le Li、Robert J. Mayer、David S. Stephenson、Peter Mayer、Armin R. Ofial、Herbert Mayr

  DOI：10.1002/chem.202201376

  日期：2022.10.4

  Enamines and sulfonium ylides attack the terminal nitrogen of diazoalkanes with rate-determining formation of zwitterions. The measured second-order rate constants were used to determine the one-bond electrophilicities E of the diazoalkanes. Pyrazolines obtained from the reactions of diazoalkanes with enamines are not formed by 1,3-dipolar cycloadditions, but by cyclization of hydrazonoenamines initially

  烯胺和硫叶立德攻击重氮烷烃的末端氮，并决定两性离子的形成。测得的二阶速率常数用于确定重氮烷烃的单键亲电性E。从重氮烷烃与烯胺的反应中获得的吡唑啉不是通过 1,3-偶极环加成反应形成的，而是通过最初由中间两性离子中的质子移动形成的亚肼基胺环化形成的。
• Selective beta 3 adrenergic agonists
  申请人：ELI LILLY AND COMPANY

  公开号：EP0921120A1

  公开（公告）日：1999-06-09

  The present invention is in the field of medicine, particularly in the treatment of Type II diabetes and obesity. More specifically, the present invention relates to selective b3 receptor agonists useful in the treatment of Type II diabetes and obesity. The invention provides compounds and methods of treating type II diabetes and obesity, comprising administering to a mammal in need thereof compounds of the Formula I: wherein: X1 is -OCH2-, -SCH2-, or a bond; R1 is a heterocycle of the formula: R2 and R3 are independently hydrogen, C1-C4 alkyl, or aryl; R4 is an optionally substituted heterocycle or a moiety selected from the group consisting of: X2 is a bond, or a 1 to 5 carbon straight or branched alkylene; R5 is hydrogen or C1-C4 alkyl; R6 is hydrogen or C1-C4 alkyl; or R5 and R6 combine with the carbon to which each is attached to form a C3-C6 cycloalkyl; or R6 combines with X2 and the carbon to which each is attached to form a C3-C8 cycloalkyl; or R6 combines with X2, R4, and the carbon to which each is attached to form: provided that R5 is hydrogen; R7 is hydrogen, hydroxy, cyano, oxo, COnR2, CONHR2, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 optionally substituted alkyl, (CH2)n aryl, (CH2)nheterocycle, (CH2)n optionally substituted aryl, or (CH2)n optionally substituted heterocycle; R8 is independently hydrogen, halo, or C1-C4 alkyl; R9 is halo, CN, OR10, C1-C4 alkyl, C1-C4 haloalkyl, CO2R2, CONR11R12, CONH(C1-C4 alkyl or C1-C4 alkoxy), SR2, CSNHR2, CSNR11R12, SO2R2, SOR2, NR11R12, optionally substituted aryl, optionally substituted heterocycle, or C2-C4 alkenyl substituted with CN, CO2R2, or CONR11R12; R10 is C1-C4 alkyl, C1-C4 haloalkyl, (CH2)nC3-C8 cycloalkyl, (CH2)naryl, (CH2)nheterocycle, (CH2)nC3-C8 optionally substituted cycloalkyl, (CH2)n optionally substituted aryl, or (CH2)n optionally substituted heterocycle; R11 and R12 are independently hydrogen, C1-C4 alkyl, aryl, (CH2)naryl, or combine with the nitrogen to which each is bound to form morpholinyl, piperidinyl, pyrrolidinyl, or piperazinyl; R13 is hydrogen, halo, aryl, or C1-C4 alkyl; m is 0 or 1; n is 0, 1, 2, or 3; or a pharmaceutically acceptable salt thereof.

  本发明属于医学领域，特别是 II 型糖尿病和肥胖症的治疗。更具体地说，本发明涉及用于治疗 II 型糖尿病和肥胖症的选择性 b3 受体激动剂。本发明提供了治疗 II 型糖尿病和肥胖症的化合物和方法，包括向需要的哺乳动物施用式 I 的化合物： 其中 X1是-O -、-S -或键； R1 是式中的杂环： R2 和 R3 独立地为氢、C1-C4 烷基或芳基； R4 是任选取代的杂环或选自以下组成的组的分子： X2 是键，或 1 至 5 碳直链或支链亚烷基； R5 是氢或 C1-C4 烷基 R6 是氢或 C1-C4 烷基； 或 R5 和 R6 与各自相连的碳结合形成 C3-C6 环烷基； 或 R6 与 X2 和各自相连的碳结合形成 C3-C8 环烷基； 或 R6 与 X2、R4 和各自相连的碳结合形成： 但 R5 为氢； R7 是氢、羟基、氰基、氧代、COnR2、CONHR2、C1-C4 烷基、C1-C4 烷氧基、C1-C4 卤代烷基、C1-C4 任选取代的烷基、(CH2)n 芳基、( )n 杂环、( )n 任选取代的芳基或 ( )n 任选取代的杂环； R8 独立地为氢、卤代或 C1-C4 烷基； R9 是卤素、CN、OR10、C1-C4 烷基、C1-C4 卤代烷基、CO2R2、CONR11R12、CONH（C1-C4 烷基或 C1-C4 烷氧基）、SR2、CSNHR2、CSNR11R12、SO2R2、SOR2、NR11R12、任选取代的芳基、任选取代的杂环或被 CN、CO2R2 或 CONR11R12 取代的 C2-C4 烯基； R10 是 C1-C4 烷基、C1-C4 卤代烷基、( )nC3-C8 环烷基、( )n 芳基、( )n 异环、( )nC3-C8 任选取代的环烷基、( )n 任选取代的芳基或 ( )n 任选取代的杂环； R11 和 R12 独立地为氢、C1-C4 烷基、芳基、( )芳烷基，或与各自结合的氮结合形成吗啉基、哌啶基、吡咯烷基或哌嗪基； R13 是氢、卤代、芳基或 C1-C4 烷基； m 是 0 或 1； n 是 0、1、2 或 3； 或其药学上可接受的盐。