N-(4-chloro-2-cyanophenyl)-N-(methylsulfonyl)methanesulfonamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(4-chloro-2-cyanophenyl)-N-(methylsulfonyl)methanesulfonamide
• 英文别名: N-(4-chloro-2-cyanophenyl)-N-methylsulfonylmethanesulfonamide
• 化学式: C₉H₉ClN₂O₄S₂
• 分子量: 308.766
• InChiKey: ONPVXXZVVFEPCP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  112
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-(4-chloro-2-cyanophenyl)-N-(methylsulfonyl)methanesulfonamide 在 potassium tert-butylate 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 4-amino-6-chloro-1-methyl-1H-benzo[c][1,2]thiazine 2,2-dioxide
  参考文献：
  名称：

  通过 CSIC 反应策略合成碳和杂合 5-氨基-2H-1,2-噻嗪 1,1-二氧化物

  摘要：

  在这里，我们全面介绍了我们关于合成在面 c（3,4-键）上退火的碳和异质融合的β-烯氨基-δ-磺胺嘧啶核苷的研究。这类化合物被设计为已知药理学模板的异构体对应物——按照生物等排置换原理通过面 e （5,6-键）退火的融合δ-磺胺嘧啶。该合成的起始材料是环状连氨基腈。特别是，根据化学性质和反应性，开发了几种用于 5 元和 6 元碳和杂芳族以及富含 sp 3 的 β-烯氨基腈的甲磺酰化方法。获得的N-单-或/和N,N-二甲磺酸盐被转化为相应的N-甲基甲磺酰胺，对其进行CSIC（碳负离子介导的磺酸盐（磺胺）分子内环化）反应方案，从而提供目标碳和杂稠合的β-烯氨基- δ -苏丹。与碳亲电试剂和异亲电试剂的反应证明了它们的合成效用。

  DOI：

  10.1016/j.tet.2022.132685
• 作为产物：
  描述：

  2-氨基-5-氯苯腈 、 甲基磺酰氯 在 盐酸 、 乙酸乙酯 、 Brine 、 Sodium sulfate-III 、 乙腈 、 乙醚 作用下， 以 吡啶 为溶剂， 反应 18.0h， 以ether to afford the title compound (8.00 g, 79%)的产率得到N-(4-chloro-2-cyanophenyl)-N-(methylsulfonyl)methanesulfonamide
  参考文献：
  名称：

  PYRAZOLOPYRIDINES AND PYRAZOLOPYRIMIDINES

  摘要：

  一种具有以下结构的化合物：或其药学上可接受的盐，或该化合物或其药学上可接受的盐的药学上可接受的溶剂，其中A和A'独立地为C或N，其中C可以是未取代的或被卤素或C1-C6烷基取代的；R和R0独立地选择自H，C1-C6烷基，羟基（C1-C6烷基），苯基（C1-C6烷基）和-（CH2）n-W的群，其中W为C3-C8环烷基，苯基，萘基，含有1-3个N、S和/或O原子的5-或6成员杂环或杂环，-SO2-R'，-NHSO2-R'，-NR"SO2-R'和SR'，其中R'和R"独立地为C1-C6烷基或C3-C8环烷基等；其中所述的烷基、环烷基、杂环、苯基、萘基或杂环均可以是未取代的或取代的，取代基包括苯基、杂环等；或者，R和R0以及它们结合在一起的N原子形成一个单环或双环杂环，该杂环可以是未取代的或取代的，取代基包括（a）卤素、羟基、杂环、C1-C6烷基、C1-C6烷氧基等，或（b）-（CH2）n-W，其中W为C3-C8环烷基、苯基等；R1为H、卤素或氰基；R2和R2'独立地为H、C1-C6烷基、氰基、C1-C6烷氧基、C1-C6烷硫基或C3-C8环烷基，其中烷基、烷氧基或环烷基可选地被一个或多个氟原子取代；X为键，-CO-，-CONH-，-SO2-，-SONH-或-（CH2）m-；R3为H、C1-C4烷基、苯基、萘基、含有1-3个N原子的5-或6成员杂环或杂环，或（c）2个O或S原子和0-2个N原子；其中所述的苯基、萘基、杂环或杂环可以选择性地被烷基、1个取代基-Y-R4和/或1-4个取代基R5中的每一个独立地选定的取代；但是当X为-CO-或-SO2-时，R3不为H；Y为键，-（CH2）m-或-O-；R4为（a）H、C1-C6烷基、C3-C8环烷基、卤素、氧代、-OR6、-NR7R8、-SR6、-SOR9、-SO2R9、-COR6、-OCOR6、-OCOR6、-NR6COR6、-CONR7R8等；（b）苯基或萘基，所述的苯基和萘基可以选择性地用1-5个取代基选自C1-C6烷基、C3-C8环烷基、卤素、氰基、-OR6、-NR7R8等；或（c）3到8成员饱和或部分不饱和的单环杂环等；R6为H、C1-C6烷基或C3-C8环烷基等；R7和R8独立地为H、C1-C6烷基或C3-C8环烷基，或与它们附着的氮原子一起形成含有1-2个氮原子或1个氮原子和1个氧原子的4、5或6成员饱和杂环，所述的C1-C6烷基可选地被C3-C8环烷基、卤素等取代，所述的杂环可选择性地被一个或多个C1-C6烷基或C3-C8环烷基取代；R9为C1-C6烷基或C3-C8环烷基；m和n独立地为0、1、2或3。本发明还涉及这些化合物的药学上可接受的盐及其药学上可接受的溶剂；含有这种化合物的组合物；以及这种化合物在治疗各种疾病，特别是哮喘和COPD方面的用途。

  公开号：

  US20150329542A1

文献信息

• Pyrazolopyridines and pyrazolopyrimidines
  申请人：Pfizer Inc.

  公开号：US10022376B2

  公开（公告）日：2018-07-17

  A compound having the structure: or a pharmaceutically acceptable salt or solvate thereof, wherein A and A′ are C or N, where C may be substituted by halo or C1-C6 alkyl; R and R0 are selected from the group consisting of H, C1-C6 alkyl, —(CH2)n—W, etc., where W is 5- or 6-membered heteroaryl or heterocyclic containing N, S and/or O atoms, —NR″SO2—R′, etc., where R′ and R″ are C1-C6 alkyl, etc.; wherein each alkyl, etc., may be substituted; or, R and Ro and the N atom to which they are bonded together to form a monocyclic or bicyclic heterocyclic ring, etc.; R1 is H, halo or cyano; R2 and R2′ are H, C1-C6 alkyl, etc.; X is a bond, etc.; R3 is H, C1-C4 alkyl, etc.; Y is a bond, —(CH2)m—, etc. The invention also relates to compositions and uses in the treatment of various diseases.

  具有以下结构的化合物： 或其药学上可接受的盐或溶液，其中A和A′是C或N，其中C可被卤素或C1-C6烷基取代；R和R0选自由H、C1-C6烷基、-(CH2)n-W等组成的组，其中W是含有N、S和/或O原子的5或6元杂芳基或杂环基、-NR″SO2-R′等、其中R′和R″是C1-C6烷基等；其中每个烷基等可被取代；或者，R和Ro及其所键合的N原子一起形成单环或双环杂环等；R1是H、卤代或氰基；R2和R2′是H、C1-C6烷基等；X是键等；R3是H、C1-C4烷基等；Y是键、-(CH2)m-等。本发明还涉及治疗各种疾病的组合物和用途。
• US9518052B2
  申请人：——

  公开号：US9518052B2

  公开（公告）日：2016-12-13
• [EN] PYRAZOLOPYRIDINES AND PYRAZOLOPYRIMIDINES<br/>[FR] PYRAZOLOPYRIDINES ET PYRAZOLOPYRIMIDINES
  申请人：PFIZER

  公开号：WO2015173683A1

  公开（公告）日：2015-11-19

  A compound having the structure: A compound having the structure (I) or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate of said compound or pharmaceutically acceptable salt, wherein A and A' are independently C or N, where C may be unsubstituted or substituted by halo or C1-C6 alkyl; R and R0 are independently selected from the group consisting of H, C1-C6 alkyl, hydroxy(C1-C6 alkyl), phenyl(C1-C6 alkyl), and -(CH2)n-W, where W is C3-C8 cycloalkyl, phenyl, naphthyl, 5- or 6-membered heteroaryl or heterocyclic containing 1 -3 N, S and/or 0 atoms, -SO2-R', -NHSO2-R', -NR"SO2-R' and SR', where R' and R" are independently C1-C6 alkyl or C3-C8 cycloalkyl, etc.; wherein each of said alkyl, cycloalkyl, heterocyclic, phenyl, naphthyl or heteroaryl may be unsubstituted or substituted by phenyl, heteroaryl, etc.; or, R and R0 and the N atom to which they are bonded together form a monocyclic or bicyclic heterocyclic ring which may be unsubstituted or substituted by (a) halo, hydroxy, heteroaryl, C1-C6 alkyl, C1-C6 alkoxy, etc., or (b) -(CH2)n-W, where W is C3-C8cycloalkyl, phenyl, etc.; R1 is H, halo or cyano; R2 and R2' are independently H, C1-C6 alkyl, cyano, C1-C6 alkoxy, C1-C6 alkylthio, or C3-C8 cycloalkyl where alkyl, alkoxy, or cycloalkyl is optionally substituted by one or more fluorine atoms; X is a bond, -CO-, -CONH-, -S02-, -SONH-, or -(CH2)m-; R3 is H, C1-C4 alkyl, phenyl, naphthyl, 5- or 6-membered heteroaryl or heterocyclic containing 1 -3 N atoms, a 5-membered heteroaryl or heterocyclic, etc., or (c) 2 O or S atoms and 0-2 N atoms; wherein each of said phenyl, naphthyl, heteroaryl or heterocyclic is optionally substituted by alkyl, 1 substituent -Y-R4 and/or 1 -4 substituents each independently selected from R5; with the proviso that when X is -CO- or -SO2-, R3 is not H; Y is a bond, -(CH2)m- or -O-; R4 is (a) H, C1-C6 alkyl, C3-C8 cycloalkl, halo, oxo, -OR6, -NR7R8, -SR6, -SOR9, -SO2R9, -COR6, -OCOR6, -COOR6, -NR6COR6, -CONR7R8, etc.; (b) phenyl or naphthyl, said phenyl and naphthyl being optionally substituted with 1 -5 substituents selected from C1-C6 alkyl, C3-C8 cycloalkyl, halo, cyano, -OR6, -NR7R8, etc.; or (c) a 3 to 8-membered saturated or partially unsaturated monocyclic heteroaryl, etc.; R6 is H, C1-C6 alkyl or C3-C8 cycloalkyl, etc.; R7 and R8 are each independently H, C1-C6 alkyl or C3-C8 cycloalkyl or are taken together with the nitrogen atom to which they are attached to form a 4-, 5- or 6-membered saturated heterocyclic ring containing 1 -2 nitrogen atoms or 1 nitrogen and 1 oxygen atom, said C1-C6 alkyl is optionally substituted by C3-C8 cycloalkyl, ha lo, etc., and said heterocyclic ring being optionally substituted by one or more C1-C6 alkyl or C3-C8 cycloalkyli groups; R9 is C1-C6 alkyl or C3-C8 cycloalkyl; and, m and n are independently 0, 1, 2 or 3. The invention also relates to pharmaceutically acceptable salts of these compounds and to pharmaceutically acceptable solvates thereof; to compositions containing such compounds; and to the uses of such compounds in the treatment of various diseases, particularly asthma and COPD.
• PYRAZOLOPYRIDINES AND PYRAZOLOPYRIMIDINES
  申请人：Pfizer Inc.

  公开号：US20150329542A1

  公开（公告）日：2015-11-19

  A compound having the structure: or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate of said compound or pharmaceutically acceptable salt, wherein A and A′ are independently C or N, where C may be unsubstituted or substituted by halo or C 1 -C 6 alkyl; R and R 0 are independently selected from the group consisting of H, C 1 -C 6 alkyl, hydroxy(C 1 -C 6 alkyl), phenyl(C 1 -C 6 alkyl), and —(CH 2 ) n —W, where W is C 3 -C 8 cycloalkyl, phenyl, naphthyl, 5- or 6-membered heteroaryl or heterocyclic containing 1-3 N, S and/or O atoms, —SO 2 —R′, —NHSO 2 —R′, —NR″SO 2 —R′ and SR′, where R′ and R″ are independently C 1 -C 6 alkyl or C 3 -C 8 cycloalkyl, etc.; wherein each of said alkyl, cycloalkyl, heterocyclic, phenyl, naphthyl or heteroaryl may be unsubstituted or substituted by phenyl, heteroaryl, etc.; or, R and R 0 and the N atom to which they are bonded together form a monocyclic or bicyclic heterocyclic ring which may be unsubstituted or substituted by (a) halo, hydroxy, heteroaryl, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, etc., or (b) —(CH 2 ) n —W, where W is C 3 -C 8 cycloalkyl, phenyl, etc.; R 1 is H, halo or cyano; R 2 and R 2′ are independently H, C 1 -C 6 alkyl, cyano, C 1 -C 6 alkoxy, C 1 -C 6 alkylthio, or C 3 -C 8 cycloalkyl where alkyl, alkoxy, or cycloalkyl is optionally substituted by one or more fluorine atoms; X is a bond, —CO—, —CONH—, —SO 2 —, —SONH—, or —(CH 2 ) m —; R 3 is H, C 1 -C 4 alkyl, phenyl, naphthyl, 5- or 6-membered heteroaryl or heterocyclic containing 1-3 N atoms, a 5-membered heteroaryl or heterocyclic, etc., or (c) 2 O or S atoms and 0-2 N atoms; wherein each of said phenyl, naphthyl, heteroaryl or heterocyclic is optionally substituted by alkyl, 1 substituent —Y—R 4 and/or 1-4 substituents each independently selected from R 5 ; with the proviso that when X is —CO— or —SO 2 —, R 3 is not H; Y is a bond, —(CH 2 ) m — or —O—; R 4 is (a) H, C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, halo, oxo, —OR 6 , —NR 7 R 8 , —SR 6 , —SOR 9 , —SO 2 R 9 , —COR 6 , —OCOR 6 , —OCOR 6 , —NR 6 COR 6 , —CONR 7 R 8 , etc.; (b) phenyl or naphthyl, said phenyl and naphthyl being optionally substituted with 1-5 substituents selected from C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, halo, cyano, —OR 6 , —NR 7 R 8 , etc.; or (c) a 3 to 8-membered saturated or partially unsaturated monocyclic heteroaryl, etc.; R 6 is H, C 1 -C 6 alkyl or C 3 -C 8 cycloalkyl, etc.; R 7 and R 8 are each independently H, C 1 -C 6 alkyl or C 3 -C 8 cycloalkyl or are taken together with the nitrogen atom to which they are attached to form a 4-, 5- or 6-membered saturated heterocyclic ring containing 1-2 nitrogen atoms or 1 nitrogen and 1 oxygen atom, said C 1 -C 6 alkyl is optionally substituted by C 3 -C 8 cycloalkyl, halo, etc., and said heterocyclic ring being optionally substituted by one or more C 1 -C 6 alkyl or C 3 -C 8 cycloalkyl groups; R 9 is C 1 -C 6 alkyl or C 3 -C 8 cycloalkyl; and, m and n are independently 0, 1, 2 or 3. The invention also relates to pharmaceutically acceptable salts of these compounds and to pharmaceutically acceptable solvates thereof; to compositions containing such compounds; and to the uses of such compounds in the treatment of various diseases, particularly asthma and COPD.

  具有以下结构的化合物： 或其药学上可接受的盐，或所述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和A′独立地为C或N，其中C可以是未取代的或由卤素或C 1 -C 6 烷基取代的；R和R 0 独立地选自H、C 1 -C 6 烷基、羟基(C 1 -C 6 烷基)、苯基(C 1 -C 6 烷基)和—(CH 2 ) n —W的群，其中W为C 3 -C 8 环烷基、苯基、萘基、含有1-3个N、S和/或O原子的5-或6元杂环芳基或杂环烷基，—SO 2 —R′、—NHSO 2 —R′、—NR″SO 2 —R′和SR′，其中R′和R″独立地为C 1 -C 6 烷基或C 3 -C 8 环烷基等；其中所述的每个烷基、环烷基、杂环、苯基、萘基或杂芳基可以是未取代的或由苯基、杂芳基等取代的；或者，R和R 0 以及它们结合的N原子共同形成一个可以是未取代的或由(a)卤素、羟基、杂芳基、C 1 -C 6 烷基、C 1 -C 6 烷氧基等取代的单环或双环杂环环，或(b) —(CH 2 ) n —W，其中W为C 3 -C 8 环烷基、苯基等；R 1 为H、卤素或氰基；R 2 和R 2′ 独立地为H、C 1 -C 6 烷基、氰基、C 1 -C 6 烷氧基、C 1 -C 6 烷硫基或C 3 -C 8 环烷基，其中烷基、烷氧基或环烷基可以选择性地由一个或多个氟原子取代；X为键，—CO—、—CONH—、—SO 2 —、—SONH—或—(CH 2) m —；R 3 为H、C 1 -C 4 烷基、苯基、萘基、含有1-3个N原子的5-或6元杂环芳基或杂环，一种5元杂环芳基或杂环等，或(c) 2个O或S原子和0-2个N原子；其中所述的每个苯基、萘基、杂芳基或杂环可以选择性地由烷基、1个取代基—Y—R 4 和/或1-4个独立选择自R 5 的取代基取代；但是当X为—CO—或—SO 2 —时，R 3 不是H；Y为键，—(CH 2) m —或—O—；R 4 为(a) H、C 1 -C 6 烷基、C 3 -C 8 环烷基、卤素、氧代、—OR 6 、—NR 7 R 8 、—SR 6 、—SOR 9 、—SO 2 R 9 、—COR 6 、—OCOR 6 、—OCOR 6 、—NR 6 COR 6 、—CONR 7 R 8 等；(b)苯基或萘基，所述的苯基和萘基可以选择性地由1-5个取代基选自C 1 -C 6 烷基、C 3 -C 8 环烷基、卤素、氰基、—OR 6 、—NR 7 R 8 等取代；或(c) 3到8元饱和或部分不饱和的单环杂芳基等；R 6 为H、C 1 -C 6 烷基或C 3 -C 8 环烷基等；R 7 和R 8 独立地为H、C 1 -C 6 烷基或C 3 -C 8 环烷基，或者与它们连接的氮原子共同形成含有1-2个氮原子或1个氮原子和1个氧原子的4、5或6元饱和杂环环，所述的C 1 -C 6 烷基可以选择性地由C 3 -C 8 环烷基、卤素等取代，所述的杂环环可以选择性地由一个或多个C 1 -C 6 烷基或C 3 -C 8 环烷基基团取代；R 9 为C 1 -C 6 烷基或C 3 -C 8 环烷基；m和n独立地为0、1、2或3。该发明还涉及这些化合物的药学上可接受的盐和其药学上可接受的溶剂；含有这种化合物的组合物；以及这种化合物在治疗各种疾病，特别是哮喘和慢性阻塞性肺病中的用途。
• Synthesis of carbo- and heterofused 5-amino-2H-1,2-thiazine 1,1-dioxides via the CSIC reaction strategy
  作者：Maksim S. Dyachenko、Yaroslav O. Chuchvera、Alexey V. Dobrydnev、Andriy I. Frolov、Eugeniy N. Ostapchuk、Maria V. Popova、Yulian M. Volovenko

  DOI：10.1016/j.tet.2022.132685

  日期：2022.3

  studies with respect to the synthesis of carbo- and heterofused β-enamino-δ-sultams annelated on face c (3,4-bond). This class of compounds was designed as isomeric counterpart of known pharmacological templates – fused δ-sultams annelated through a face e (5,6-bond) following the principles of bioisosteric replacement. The starting material for this synthesis is cyclic vicinal amino nitriles. In particular

  在这里，我们全面介绍了我们关于合成在面 c（3,4-键）上退火的碳和异质融合的β-烯氨基-δ-磺胺嘧啶核苷的研究。这类化合物被设计为已知药理学模板的异构体对应物——按照生物等排置换原理通过面 e （5,6-键）退火的融合δ-磺胺嘧啶。该合成的起始材料是环状连氨基腈。特别是，根据化学性质和反应性，开发了几种用于 5 元和 6 元碳和杂芳族以及富含 sp 3 的 β-烯氨基腈的甲磺酰化方法。获得的N-单-或/和N,N-二甲磺酸盐被转化为相应的N-甲基甲磺酰胺，对其进行CSIC（碳负离子介导的磺酸盐（磺胺）分子内环化）反应方案，从而提供目标碳和杂稠合的β-烯氨基- δ -苏丹。与碳亲电试剂和异亲电试剂的反应证明了它们的合成效用。