6-Amino-2-chloropyrimidine-4-carboxylic acid | 16492-29-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 6-Amino-2-chloropyrimidine-4-carboxylic acid
• 英文别名: 6-amino-2-chloropyrimidine-4-carboxylic acid
• CAS: 16492-29-8
• 化学式: C₅H₄ClN₃O₂
• 分子量: 173.56
• InChiKey: UHGBKWYISOUYAE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  89.1
• 氢给体数：
  2
• 氢受体数：
  5

文献信息

• METHODS FOR PRODUCING BORYLATED ARENES
  申请人：Dow AgroSciences, LLC

  公开号：US20150065743A1

  公开（公告）日：2015-03-05

  Methods for the selective borylation of arenes, including arenes substituted with an electron-withdrawing group (e.g., 1-chloro-3-fluoro-2-substituted benzenes) are provided. The methods can be used, in some embodiments, to efficiently and regioselectively prepare borylated arenes without the need for expensive cryogenic reaction conditions.

  提供了一种选择性硼化芳烃的方法，包括带有电子吸引基团的芳烃（例如，1-氯-3-氟-2-取代苯）。在某些实施方式中，这些方法可以用来高效和区域选择性地制备硼化芳烃，而无需昂贵的低温反应条件。
• [EN] METHODS OF FORMING 4-CHLORO-2-FLUORO-3-SUBSTITUTED-PHENYLBORONIC ACID PINACOL ESTERS AND METHODS OF USING THE SAME<br/>[FR] PROCÉDÉS DE FORMATION D'ESTERS PINACOLIQUES D'ACIDE 4-CHLORO-2-FLUORO-3-SUBSTITUÉ-PHÉNYLBORONIQUE ET LEURS PROCÉDÉS D'UTILISATION
  申请人：DOW AGROSCIENCES LLC

  公开号：WO2013101665A1

  公开（公告）日：2013-07-04

  Methods include formation of 4-chloro-2 fluoro-3 substituted-phenylboronic acid pinacol esters. The method comprises contacting a 1-chloro-3-fluoro-2-substituted benzene with an alkyl lithium to form a lithiated 1-chloro-3-fluoro-2-substituted benzene. The lithiated 1-chloro-3-fluoro-2-substituted benzene is contacted with an electrophilic boronic acid derivative to form a 4-chloro-2-fluoro-3-substituted-phenylboronate. The 4-chloro-2-fluoro-3-substituted-phenylboronate is reacted with an aqueous base to form a (4-chloro-2-fluoro-3-substituted phenyl)trihydroxyborate. The (-chloro-2-fluoro-3-substituted phenyl)trihydroxyborate is reacted with an acid to form a 4-chloro-2-fluoro-3-substituted phenylboronic acid. The 4-chloro-2-fluoro-3-substituted phenylboronic acid is reacted with 2,3 dimethyl 2,3 butanediol to form 4-chloro-2-fluoro-3-substituted phenylboronic acid pinacol esters. Methods of using 4-chloro-2-fluoro-3-substituted phenylboronic acid pinacol esters to produce 6 (4-chloro-2-fluoro-3-substituted phenyl) 4 aminopicolinates are also disclosed.

  方法包括形成4-氯-2-氟-3-取代苯硼酸皮纳醇酯。该方法包括将1-氯-3-氟-2-取代苯与烷基锂接触，形成锂化的1-氯-3-氟-2-取代苯。然后将锂化的1-氯-3-氟-2-取代苯与亲电性硼酸衍生物接触，形成4-氯-2-氟-3-取代苯硼酸酯。接着将4-氯-2-氟-3-取代苯硼酸酯与水性碱反应，形成(4-氯-2-氟-3-取代苯)三羟基硼酸酯。将(-氯-2-氟-3-取代苯)三羟基硼酸酯与酸反应，形成4-氯-2-氟-3-取代苯硼酸。最后，将4-氯-2-氟-3-取代苯硼酸与2,3-二甲基-2,3-丁二醇反应，形成4-氯-2-氟-3-取代苯硼酸皮纳醇酯。此外，还披露了使用4-氯-2-氟-3-取代苯硼酸皮纳醇酯制备6-(4-氯-2-氟-3-取代苯)4-氨基吡啶酸酯的方法。
• [EN] SYNTHESIS OF 6-ARYL-4-AMINOPICOLINATES AND 2-ARYL-6-AMINOPYRIMIDINE-4-CARBOXYLATES BY DIRECT SUZUKI COUPLING<br/>[FR] SYNTHÈSE DE 6-ARYL-4-AMINOPICOLINATES ET DE 2-ARYL-6-AMINOPYRIMIDINE-4-CARBOXYLATES PAR COUPLAGE DIRECT DE SUZUKI
  申请人：DOW AGROSCIENCES LLC

  公开号：WO2017201377A1

  公开（公告）日：2017-11-23

  Improved methods of synthesizing 6-aryl-4-aminopicolinates, such as arylalky and alkyl 4-amino-3-chloro-6-(4-chloro-2-fluoro-3-methoxyphenyl)pyridine-2-carboxylates and arylalkyl and alkyl 4-amino-3-chloro-5-fluoro-6-(4-chloro-2-fluoro-3-methoxyphenyl)pyridine-2- carboxylates, are described herein. The improved methods include a direct Suzuki coupling step, which eliminates the protection/de-protection steps in the current chemical process, and therefore eliminates or reduces various raw materials, equipment and cycle time as well as modification of other process conditions including use of crude AP, use of ABA-diMe, and varying pH, catalyst concentration, solvent composition, and/or workup procedures. This invention was expanded to include synthesis of 2-aryl-6-aminopyrimidine-4-carboxylates.

  本文介绍了合成6-芳基-4-氨基吡啶酸盐的改进方法，例如芳基烷基和烷基4-氨基-3-氯-6-(4-氯-2-氟-3-甲氧基苯基)吡啶-2-羧酸酯和芳基烷基和烷基4-氨基-3-氯-5-氟-6-(4-氯-2-氟-3-甲氧基苯基)吡啶-2-羧酸酯。改进的方法包括直接的Suzuki偶联步骤，消除了当前化学过程中的保护/脱保护步骤，因此消除或减少了各种原材料、设备和周期时间，以及改变其他工艺条件，包括使用粗AP、使用ABA-diMe、改变pH、催化剂浓度、溶剂组成和/或工作程序。本发明还扩展到包括合成2-芳基-6-氨基嘧啶-4-羧酸盐。
• [EN] METHODS OF ISOLATING (4-CHLORO-2-FLUORO-3-SUBSTITUTED-PHENYL) BORONATES AND METHODS OF USING THE SAME<br/>[FR] PROCÉDÉS D'ISOLEMENT DE PHÉNYLBORONATES 4-CHLORO-2-FLUORO-3 SUBSTITUÉS ET LEURS PROCÉDÉS D'UTILISATION
  申请人：DOW AGROSCIENCES LLC

  公开号：WO2013101987A1

  公开（公告）日：2013-07-04

  Methods of isolating a 4-chloro-2-fluoro-3-substituted-phenylboronate include adding carbon dioxide gas or carbon dioxide solid (dry ice) to a solution comprising a 4-chloro-2-fluoro-3-substituted-phenylboronate, an inert organic solvent, and at least one lithium salt to react the at least one lithium salt with the carbon dioxide gas or carbon dioxide solid (dry ice) and form a mixture comprising the 4-chloro-2-fluoro-3- substituted-phenylboronate, the inert organic solvent, and a precipitated solid. The precipitated solid may be removed from the mixture. Methods of using 4-chloro-2- fluoro-3-substituted-phenylboronates to produce methyl-4-amino-3-chloro-6-(4-chloro- 2-fluoro-3-substituted-phenyl)pyridine-2-carboxylates are also disclosed. A 4-chloro-2-fluoro-3-substituted-phenylboronate produced by one of the methods of isolating a 4-chloro-2-fluoro-3-substituted-phenylboronate is also disclosed, wherein the 4-chloro-2-fluoro-3-substituted-phenylboronate may be obtained at a yield of greater than or equal to about 90%.

  分离4-氯-2-氟-3-取代苯基硼酸酯的方法包括向包含4-氯-2-氟-3-取代苯基硼酸酯、惰性有机溶剂和至少一种锂盐的溶液中加入二氧化碳气体或二氧化碳固体（干冰），以使至少一种锂盐与二氧化碳气体或二氧化碳固体（干冰）反应并形成包含4-氯-2-氟-3-取代苯基硼酸酯、惰性有机溶剂和沉淀固体的混合物。可以从混合物中去除沉淀固体。还公开了使用4-氯-2-氟-3-取代苯基硼酸酯制备甲基-4-氨基-3-氯-6-（4-氯-2-氟-3-取代苯基）吡啶-2-羧酸甲酯的方法。还公开了一种由分离4-氯-2-氟-3-取代苯基硼酸酯的方法之一生产的4-氯-2-氟-3-取代苯基硼酸酯，其中4-氯-2-氟-3-取代苯基硼酸酯的收率可以达到大约90％或更高。
• METHODS OF FORMING 4-CHLORO-2-FLUORO-3-SUBSTITUTED-PHENYLBORONIC ACID PINACOL ESTERS AND METHODS OF USING THE SAME
  申请人：DOW AGROSCIENCES LLC

  公开号：US20130172565A1

  公开（公告）日：2013-07-04

  Methods include formation of 4-chloro-2-fluoro-3-substituted-phenylboronic acid pinacol esters. The method comprises contacting a 1-chloro-3-fluoro-2-substituted benzene with an alkyl lithium to form a lithiated 1-chloro-3-fluoro-2-substituted benzene. The lithiated 1-chloro-3-fluoro-2-substituted benzene is contacted with an electrophilic boronic acid derivative to form a 4-chloro-2-fluoro-3-substituted-phenylboronate. The 4-chloro-2-fluoro-3-substituted-phenylboronate is reacted with an aqueous base to form a (4-chloro-2-fluoro-3-substituted-phenyl)trihydroxyborate. The (4-chloro-2-fluoro-3-substituted-phenyl)trihydroxyborate is reacted with an acid to form a 4 chloro-2-fluoro-3-substituted-phenylboronic acid. The 4-chloro-2-fluoro-3-substituted-phenylboronic acid is reacted with 2,3-dimethyl-2,3-butanediol to form 4-chloro-2-fluoro-3-substituted-phenylboronic acid pinacol esters. Methods of using 4-chloro-2-fluoro-3-substituted-phenylboronic acid pinacol esters to produce 6-(4-chloro-2-fluoro-3-substituted-phenyl)-4-aminopicolinates are also disclosed.

  方法包括形成4-氯-2-氟-3-取代苯硼酸皮纳科酯。该方法包括将1-氯-3-氟-2-取代苯与烷基锂接触，以形成锂化的1-氯-3-氟-2-取代苯。将锂化的1-氯-3-氟-2-取代苯与亲电性硼酸衍生物接触，以形成4-氯-2-氟-3-取代苯基硼酸酯。将4-氯-2-氟-3-取代苯基硼酸酯与水基碱反应，以形成(4-氯-2-氟-3-取代苯)三羟基硼酸酯。将(4-氯-2-氟-3-取代苯)三羟基硼酸酯与酸反应，以形成4-氯-2-氟-3-取代苯硼酸。4-氯-2-氟-3-取代苯硼酸与2,3-二甲基-2,3-丁二醇反应，以形成4-氯-2-氟-3-取代苯硼酸皮纳科酯。还公开了使用4-氯-2-氟-3-取代苯硼酸皮纳科酯制备6-(4-氯-2-氟-3-取代苯)-4-氨基吡啶酸酯的方法。