2-异丙基-1,3-噻唑-4-甲酰胺 | 390386-23-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 2-异丙基-1,3-噻唑-4-甲酰胺
• 中文别名: 2-丁烯二酸,2-[(2-氯-3-甲氧苯基)氨基]-,1,4-二甲基酯
• 英文名称: 2-isopropylthiazole-4-carboxylic acid amide
• 英文别名: 2-isopropylthiazole-4-carboxylic amide；2-Isopropylthiazole-4-carboxamide；2-propan-2-yl-1,3-thiazole-4-carboxamide
• CAS: 390386-23-9
• 化学式: C₇H₁₀N₂OS
• mdl: MFCD18821089
• 分子量: 170.235
• InChiKey: ZHTIQAPVCFSHDH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.428
• 拓扑面积：
  84.2
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2934100090

反应信息

• 作为反应物：
  描述：

  2-异丙基-1,3-噻唑-4-甲酰胺 在 劳森试剂 、 咪唑 、 锂硼氢 、 碘 、 三苯基膦 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 乙醇 、 正己烷 、 苯 为溶剂， 反应 16.75h， 生成 (+)-cystothiazole A
  参考文献：
  名称：

  基于钯催化的环化-甲氧基羰基化的（+）-巯基噻唑A的新全合成

  摘要：

  衍生自（2 R，3 S）-环氧丁酸酯7的（2 R，3 S）-3-甲基戊4炔-1,2-二醇（6）的钯催化环化-甲氧基羰基化，然后甲基化得到四氢乙酸-2-亚呋喃酯（-）- 10，其被转化为左半醛（+）- 3。使用双（三甲基甲硅烷基）氨基锂，（+）- 4与衍生自苄基唑型碘化4 4的磷酰内酯之间的维蒂希反应，得到（+）-巯基噻唑A（2）。

  DOI：

  10.1016/s0040-4020(03)00300-4
• 作为产物：
  描述：

  2-异丙基噻唑-4-羧酸乙酯 在 氨 作用下， 以 甲醇 为溶剂， 反应 15.0h， 以87%的产率得到2-异丙基-1,3-噻唑-4-甲酰胺
  参考文献：
  名称：

  巯基噻唑A和C的全合成

  摘要：

  已经描述了在对映体控制的巯基噻唑A和C的制备中达到有效的途径。cystothiazoles在细胞色素bc（1）复合物的特定位点表现出有效的抗真菌活性，并作为线粒体氧化的新型抑制剂发挥作用。这些研究概述了一个总的和灵活的计划，可以很容易地适用于各种相关的五元杂环系统的合成和结构-活性关系的生物学研究。核心[2,4']双噻唑组分8分六个步骤制备，使用霍纳-埃蒙斯烯化反应生成α，β-不饱和酯10为不对称埃文斯羟醛羟醛工艺奠定了基础，该工艺建立了所需的C（4）/ C（5）立体化学。

  DOI：

  10.1021/jo0106905

文献信息

• [EN] SUBSTITUTED PIPERAZINES OF AZEPINES, OXAZEPINES, AND THIAZEPINES<br/>[FR] PIPERAZINES SUBSTITUTEES D'AZEPINES, D'OXAZEPINES, ET DE THIAZEPINES
  申请人：LILLY CO ELI

  公开号：WO2005026177A1

  公开（公告）日：2005-03-24

  Described herein are antipyschotic compounds of formula (I) wherein: is an optionally benzo-fused five or six member aromatic ring having zero to three hetero atoms independently selected from N, O, and S; R1 is hydrogen, (C1-6) fluoroalkyl, (C3-6) cycloalkyl, or (C1-4) alkyl, wherein the (C1-4) alkyl is unsubstituted or substituted with hydroxy, methoxy, ethoxy, OCH2CH2OH, -CN, imidazolidin-2-one, phenyl, or tetrazole wherein tetrazole is unsubstituted or substituted with (C1-4) alkyl; R2 is H, halogen, (C1-6) fluoroalkyl, (C3-6) cycloalkyl, OR6, SR6, NO2, CN, COR6, C(O)OR6, C(OH)R6, CONR7R8, phenyl or (C1-6) alkyl, wherein the (C1-6) alkyl is unsubstituted or substituted with a hydroxy; R3 is hydrogen, (C 1-6)fluoroalkyl , (C3-6) cycloalkyl, (C 2-6) alkenyl, phenyl, monocyclic heteroaromatic, bicyclic heteroaromatic, or (C1-4)alkyl wherein (C1-4) alkyl is unsubstituted or substituted with a phenyl; R4 and R5 are independently selected from hydrogen, halogen, (C1-6) alkyl, (C1-6) fluoroalkyl, OR9, SR9, NO2, CN, or COR9; R6 is hydrogen, (C1-6) fluoroalkyl, or (C1-6) alkyl; R7 and R8 are independently hydrogen, or (C1-6) alkyl; R9 is hydrogen, (C1-6) fluoroalkyl, (C1-6) alkyl; Alk is (C1-4) alkylene unsubstituted or substituted with a hydroxy; Y is oxygen, sulfur, SO2, or a bond; X is CH2, C=O, S, O, or SO2; Z is hydrogen, halogen, (C1-6) alkyl, (C1-6)fluoroalkyl, -OH, (C1-6) alkoxy, (C1-6) fluoroalkoxy, (C1-6) alkylthio, (C1-6) acyl, (C1-4)alkylsulfonyl, -OCF3, -NO2, - CN, carboxamido which may be substituted on the nitrogen by one or two (C1-4) alkyl groups, and -NH2 in which one of the hydrogens may be replaced by a (C1-4) alkyl group and the other hydrogen may be replaced by either a (C1-4) alkyl group, a (C1-6) acyl group, or a (C1-4) alkylsulfonyl group; the phenyl of R1, R2 or R3 is independently unsubstituted or substituted with one to three substituents independently selected from Z; the monocyclic heteroaromatic of R3 is unsubstituted or substituted with one to three substituents independently selected from Z; the bicyclic heteroaromatic of R3 is unsubstituted or substituted with one to three substituents independently selected from Z; and salts, solvates, and crystal forms thereof. Also described are the use of the compounds of formula (I) as antagonists of the dopamine D2 receptor and as agents for the treatment of psychosis and bipolar disorders, and pharmaceutical formulations of the compounds of formula (I).

  本文描述了式(I)的抗精神病化合物，其中：是一个可选的苯并五元或六元芳香环，其中含有零至三个异原子，独立选择自N、O和S；R1是氢，(C1-6)氟烷基，(C3-6)环烷基，或(C1-4)烷基，其中(C1-4)烷基未取代或取代为羟基、甲氧基、乙氧基、O OH、-CN、咪唑烷-2-酮、苯基或四氮唑，其中四氮唑未取代或取代为(C1-4)烷基；R2是H、卤素、(C1-6)氟烷基、(C3-6)环烷基、OR6、SR6、NO2、CN、COR6、C(O)OR6、C(OH)R6、CONR7R8、苯基或(C1-6)烷基，其中(C1-6)烷基未取代或取代为羟基；R3是氢，(C1-6)氟烷基，(C3-6)环烷基，(C2-6)烯基，苯基，单环杂芳基，双环杂芳基，或(C1-4)烷基，其中(C1-4)烷基未取代或取代为苯基；R4和R5独立选择自氢、卤素、(C1-6)烷基、(C1-6)氟烷基、OR9、SR9、 、CN或COR9；R6是氢、(C1-6)氟烷基或(C1-6)烷基；R7和R8独立选择自氢或(C1-6)烷基；R9是氢、(C1-6)氟烷基或(C1-6)烷基；Alk是未取代或取代为羟基的(C1-4)烷基；Y是氧、硫、SO2或键；X是CH2、C=O、S、O或SO2；Z是氢、卤素、(C1-6)烷基、(C1-6)氟烷基、-OH、(C1-6)烷氧基、(C1-6)氟烷氧基、(C1-6)烷硫基、(C1-6)酰基、(C1-4)烷基磺酰基、-OCF3、- 、-CN、羧酰胺基，该羧酰胺基可在氮上被一个或两个(C1-4)烷基取代，以及-NH2，其中一个氢原子可被(C1-4)烷基取代，另一个氢原子可被(C1-4)烷基、(C1-6)酰基或(C1-4)烷基磺酰基取代；R1、R2或R3的苯基独立地未取代或取代为从Z中独立选择的一个至三个取代基；R3的单环杂芳基未取代或取代为从Z中独立选择的一个至三个取代基；R3的双环杂芳基未取代或取代为从Z中独立选择的一个至三个取代基；以及其盐、溶剂化合物和晶型形式。还描述了将式(I)的化合物用作多巴胺D2受体拮抗剂和治疗精神病和双相情感障碍的药物，以及式(I)的药物配方。
• [EN] HETEROARYLMETHYL AMIDES<br/>[FR] HÉTÉROARYLMÉTHYL-AMIDES
  申请人：HOFFMANN LA ROCHE

  公开号：WO2012032018A1

  公开（公告）日：2012-03-15

  The present invention relates to compounds of the formula I wherein A1, A2, A3 and R1 to R8 are defined in the description, and to pharmaceutically acceptable salts thereof, their manufacture, pharmaceutical compositions containing them and their use as medicaments for the treatment and/or prophylaxis of diseases which can be treated with HDL-cholesterol raising agents, such as particularly dyslipidemia, atherosclerosis and cardiovascular diseases.

  本发明涉及公式I中的化合物，其中A1、A2、A3和R1至R8在描述中有定义，以及其药用盐，其制备方法，含有它们的药物组合物以及它们作为药物用于治疗和/或预防可以用HDL-胆固醇升高剂治疗的疾病，如特别是脂质代谢异常、动脉粥样硬化和心血管疾病。
• Alternative synthesis of cystothiazole A
  作者：Hiroyuki Akita、Noriyuki Sutou、Takamitsu Sasaki、Keisuke Kato

  DOI：10.1016/j.tet.2006.09.064

  日期：2006.12

  3S)-epoxy butanoate 5 gave the acetylenic ester 10, which was treated with MeOH in the presence of Bu3P to afford selectively (Z)-β-methoxy acrylate congener 11 in 86% yield. Treatment of (Z)-11 with 99.8% enrichment of CDCl3 followed by consecutive desilylation and oxidation afforded the left-half aldehyde (+)-2. The overall yield (10 steps from 5; 23%) of (+)-2 via the present route was improved in comparison

  （ - ） - （2-的钯催化的甲氧基羰基- [R，3小号）-1-叔-butyldimethylsiloxy -3-甲基-2- methoxypenta -4-炔9衍生自（2 - [R，3小号） -环氧丁酸酯5，得到炔酸酯10，在Bu 3 P存在下用MeOH处理，以86％的收率选择性提供（Z）-β-甲氧基丙烯酸酯同类物11。用99.8％的CDCl 3富集处理（Z）-11，然后连续进行甲硅烷基化和氧化，得到左半醛（+）- 2。总产率（从10个步骤5 ; 23％） -的（+）2经由本路线被相较于（从10步提高5 ;先前报道的路线的10％）。通过将修改Julia的联接方法，选择性（Ë / ž = 14：1）的（ë） -形式（cystothiazole阿1）抵靠（Ž）构型在相比于维悌希方法改善（Ë / ž = 4：1至6.9：1）。
• New total synthesis of (+)-cystothiazole A
  作者：Keisuke Kato、Akira Nishimura、Yasuhiro Yamamoto、Hiroyuki Akita

  DOI：10.1016/s0040-4039(01)02207-9

  日期：2002.1

  3S)-epoxy butanoate 8 followed by methylation gave the tetrahydro-2-furylidene acetate (−)-9, which was converted to the left-half aldehyde (+)-4. A Wittig reaction between (+)-4 and the phosphoranylide derived from the bithiazole-type phosphonium iodide 5 using lithium bis(trimethylsilyl)amide afforded the (+)-cystothiazole A (2).

  由（2 R，3 S）-环氧丁酸酯8衍生的（2 R，3 S）-3-甲基戊4炔-1,2-二醇（7）的钯催化环化-甲氧基羰基化，然后甲基化得到四氢乙酸-2-亚呋喃酯（-）- 9，将其转化为左半醛（+）- 4。使用双（三甲基甲硅烷基）酰胺锂，（+）- 4与衍生自苄基唑型碘化5 5的磷酰内酯之间的维蒂希反应，得到（+）-巯基噻唑A（2）。
• Substituted piperazines of azepines, oxazepines and thiazepines
  申请人：He Xiaoqiang John

  公开号：US20060270656A1

  公开（公告）日：2006-11-30

  Described herein are antipyschotic compounds of formula (I) wherein: is an optionally benzo-fused five or six member aromatic ring having zero to three hetero atoms independently selected from N, O, and S; R 1 is hydrogen, (C 1-6 ) fluoroalkyl, (C 3-6 ) cycloalkyl, or (C 1-4 ) alkyl, wherein the (C 1-4 ) alkyl is unsubstituted or substituted with hydroxy, methoxy, ethoxy, OCH 2 CH 2 OH, —CN, imidazolidin-2-one, phenyl, or tetrazole wherein tetrazole is unsubstituted or substituted with (C 1-4 ) alkyl; R 2 is H, halogen, (C 1-6 ) fluoroalkyl, (C 3-6 ) cycloalkyl, OR 6 , SR 6 , NO 2 , CN, COR 6 , C(O)OR 6 , C(OH)R 6 , CONR 7 R 8 , phenyl or (C 1-6 ) alkyl, wherein the (C 1-6 ) alkyl is unsubstituted or substituted with a hydroxy; R 3 is hydrogen, (C 1-6 )fluoroalkyl , (C 3-6 ) cycloalkyl, (C 2-6 ) alkenyl, phenyl, monocyclic heteroaromatic, bicyclic heteroaromatic, or (C 1-4 )alkyl wherein (C 1-4 ) alkyl is unsubstituted or substituted with a phenyl; R 4 and R 5 are independently selected from hydrogen, halogen, (C 1-6 ) alkyl, (C 1-6 ) fluoroalkyl, OR 9 , SR 9 , NO 2 , CN, or COR 9 ; R 6 is hydrogen, (C 1-6 ) fluoroalkyl, or (C 1-6 ) alkyl; R 7 and R 8 are independently hydrogen, or (C 1-6 ) alkyl; R 9 is hydrogen, (C 1-6 ) fluoroalkyl, (C 1-6 ) alkyl; Alk is (C 1-4 ) alkylene unsubstituted or substituted with a hydroxy; Y is oxygen, sulfur, SO 2 , or a bond; X is CH 2 , C═O, S, O, or SO 2 ; Z is hydrogen, halogen, (C 1-6 ) alkyl, (C 1-6 )fluoroalkyl, —OH, (C 1-6 ) alkoxy, (C 1-6 ) fluoroalkoxy, (C 1-6 ) alkylthio, (C 1-6 ) acyl, (C 1-4 )alkylsulfonyl, —OCF 3 , —NO 2 , —CN, carboxamido which may be substituted on the nitrogen by one or two (C 1-4 ) alkyl groups, and —NH 2 in which one of the hydrogens may be replaced by a (C 1-4 ) alkyl group and the other hydrogen may be replaced by either a (C 1-4 ) alkyl group, a (C 1-6 ) acyl group, or a (C 1-4 ) alkylsulfonyl group; the phenyl of R 1 , R 2 or R 3 is independently unsubstituted or substituted with one to three substituents independently selected from Z; the monocyclic heteroaromatic of R 3 is unsubstituted or substituted with one to three substituents independently selected from Z; the bicyclic heteroaromatic of R 3 is unsubstituted or substituted with one to three substituents independently selected from Z; and salts, solvates, and crystal forms thereof. Also described are the use of the compounds of formula (I) as antagonists of the dopamine D 2 receptor and as agents for the treatment of psychosis and bipolar disorders, and pharmaceutical formulations of the compounds of formula (I).

  本文描述了式(I)的抗精神病化合物，其中： - 是一个可选的苯并五元或六元芳香环，其具有0-3个杂原子，独立地选自N，O和S； - R1是氢，(C1-6)氟烷基，(C3-6)环烷基或(C1-4)烷基，其中(C1-4)烷基未取代或取代了羟基，甲氧基，乙氧基，O OH，—CN，咪唑啉-2-酮，苯基或四唑，其中四唑未取代或取代了(C1-4)烷基； - R2是H，卤素，(C1-6)氟烷基，(C3-6)环烷基，OR6，SR6，NO2，CN，COR6，C(O)OR6，C(OH)R6，CONR7R8，苯基或(C1-6)烷基，其中(C1-6)烷基未取代或取代了羟基； - R3是氢，(C1-6)氟烷基，(C3-6)环烷基，(C2-6)烯基，苯基，单环杂芳基，双环杂芳基或(C1-4)烷基，其中(C1-4)烷基未取代或取代了苯基； - R4和R5独立地选自氢，卤素，(C1-6)烷基，(C1-6)氟烷基，OR9，SR9， ，CN或COR9； - R6是氢，(C1-6)氟烷基或(C1-6)烷基； - R7和R8独立地是氢或(C1-6)烷基； - R9是氢，(C1-6)氟烷基或(C1-6)烷基； - Alk是(C1-4)烷基，未取代或取代了羟基； - Y是氧，硫，SO2或键； - X是CH2，C═O，S，O或SO2； - Z是氢，卤素，(C1-6)烷基，(C1-6)氟烷基，—OH，(C1-6)烷氧基，(C1-6)氟烷氧基，(C1-6)烷硫基，(C1-6)酰基，(C1-4)烷基磺酰基，—OCF3，— ，—CN，羧酰胺，其氮上可能通过一个或两个(C1-4)烷基取代，以及—NH2，在其中一个氢可能被(C1-4)烷基取代，另一个氢可能被(C1-4)烷基，(C1-6)酰基或(C1-4)烷基磺酰基取代； - R1，R2或R3的苯基独立地未取代或取代了1-3个Z取代基； - R3的单环杂芳基未取代或取代了1-3个Z取代基； - R3的双环杂芳基未取代或取代了1-3个Z取代基； - 还描述了该化合物的盐，溶剂化合物和晶体形式。 还描述了将式(I)化合物用作多巴胺D2受体拮抗剂和治疗精神病和双相障碍的药物，以及式(I)化合物的制剂。