6-chloro-N-(2,4-dichlorophenyl)-2-methyl-5-(2-propen-1-yl)-4-pyrimidinamine | 268547-63-3

• 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: 6-chloro-N-(2,4-dichlorophenyl)-2-methyl-5-(2-propen-1-yl)-4-pyrimidinamine
• 英文别名: 5-Allyl-4-chloro-6-(2,4-dichloroanilino)-2-methylpyrimidine；6-chloro-N-(2,4-dichlorophenyl)-2-methyl-5-prop-2-enylpyrimidin-4-amine
• CAS: 268547-63-3
• 化学式: C₁₄H₁₂Cl₃N₃
• 分子量: 328.628
• InChiKey: YYLKAQLXHJAGMB-UHFFFAOYSA-N

物化性质

• 熔点：
  94-95 °C
• 沸点：
  397.3±42.0 °C(Predicted)
• 密度：
  1.378±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  37.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-chloro-N-(2,4-dichlorophenyl)-2-methyl-5-(2-propen-1-yl)-4-pyrimidinamine 在 盐酸 、 sodium periodate 、 四氧化锇 作用下， 以 acetone - water 、 二氯甲烷 、 叔丁醇 为溶剂， 以0.929 g (50%)的产率得到4-Chloro-1-(2,4-dichlorophenyl)-6-methyl-5,7-diazaindole
  参考文献：
  名称：

  CRF receptor antagonists and methods relating thereto

  摘要：

  本发明披露了CRF受体拮抗剂，其在治疗各种疾病中具有用途，包括治疗表现为暖血动物中CRF过分分泌的疾病，如中风。本发明的CRF受体拮抗剂具有以下结构：包括其立体异构体和药学上可接受的盐，其中n、m、A、B、C、R、R1、R2和Ar的定义如本文所述。还披露了含有CRF受体拮抗剂的组合物，以及使用这些组合物的方法。

  公开号：

  US06514982B1
• 作为产物：
  描述：

  烯丙基丙二酸二乙酯 在 sodium methylate 、 sodium hydride 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 6-chloro-N-(2,4-dichlorophenyl)-2-methyl-5-(2-propen-1-yl)-4-pyrimidinamine
  参考文献：
  名称：

  Synthesis of Pyrrolopyrimidine CRF-R1 Antagonists Containing a Tricyclic Core via an Intra-molecular Heck Reaction

  摘要：

  A synthetic route to pharmaceutically important tricyclic pyrrolopyrimidines was developed. The method employs a palladium-mediated Heck cyclization as the critical step in the construction of the final six membered ring.

  DOI：

  10.3987/com-03-s(p)41

文献信息

• [EN] CONDENSED N-HETEROCYCLIC COMPOUNDS AND THEIR USE AS CRF RECEPTOR ANTAGONISTS<br/>[FR] COMPOSES N-HETEROCYCLIQUES CONDENSES ET LEUR UTILISATION COMME ANTAGONISTES DU RECEPTEUR CRF
  申请人：SB PHARMCO INC

  公开号：WO2004094419A1

  公开（公告）日：2004-11-04

  The present invention provides compounds of formula (I) including stereoisomers, prodrugs and pharmaceutically acceptable salts or solvates thereof (Formula (I)) wherein the dashed line may represent a double bond; R is aryl or heteroaryl, each of which may be substituted by 1 to 4 groups J selected from: halogen, C1-C6 alkyl, C1-C6 alkoxy, halo C1-C6 alkyl, C2-C6 .alkenyl, ,C2-C6 -alkynyl,-halo-C1=C6 -aIkoxy,-=C(O)RZ,-nitro, -hydroxy, =NR3R4i cyano, and or a group Z; R, is hydrogen, C3-C7 cycloalkyl, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 thioalkyl, C2-C6 alkenyl, C2-C6 alkynyl, halo C1-C6 alkyl, halo C1-C6 alkoxy, halogen, NR3R4or cyano; D, G is -C- optionally substituted; A is -C- optionally substituted; X is carbon or-nitrogen; Y is nitrogen or -C- optionally substituted; W is a 4-8 carbocyclic membered ring, which may be saturated or may contain one to three double bonds,, and in which: - one carbon atom is replaced by a carbonyl or S(O)m; and - one to four carbon atoms may optionally be replaced by oxygen, nitrogen or NR14, S(O)m, carbonyl, and such ring may be further substituted by I to 8 substituents; Z is a 5-6 membered heterocycle or a phenyl, which may be substituted by I to 8 substituents; m is an integer from 0 to 2, to processes for their preparation, to pharmaceutical compositions containing them and to their use in the treatment of conditions mediated by corticotropin-releasing factor (CRF).

  本发明提供了化合物的公式(I)，包括立体异构体、前药和其药学上可接受的盐或溶剂（公式(I)），其中虚线可能表示双键；R是芳基或杂环芳基，每个都可以由1到4个J组成，所选自：卤素、C1-C6烷基、C1-C6烷氧基、卤代C1-C6烷基、C2-C6烯基、C2-C6炔基、卤代C1=C6烷氧基、=C(O)RZ、硝基、羟基、=NR3R4i氰基，或Z组；R是氢、C3-C7环烷基、C1-C6烷基、C1-C6烷氧基、C1-C6硫代烷基、C2-C6烯基、C2-C6炔基、卤代C1-C6烷基、卤代C1-C6烷氧基、卤素、NR3R4或氰基；D，G是可选取代的-C-；A是可选取代的-C-；X是碳或氮；Y是氮或可选取代的-C-；W是一个4-8碳环成员环，可以饱和或含有一到三个双键，其中：-一个碳原子被羰基或S(O)m取代；和-一到四个碳原子可以选择性地被氧、氮或NR14、S(O)m、羰基取代，这样的环可能进一步由1到8个取代基取代；Z是一个5-6成员杂环或苯基，可以由1到8个取代基取代；m是一个从0到2的整数，用于它们的制备方法，含有它们的药物组合物以及它们在治疗由促肾上腺皮质激素释放因子（CRF）介导的疾病中的用途。
• Corticotropin releasing factor antagonists
  申请人：Di Fabio Romano

  公开号：US20050054661A1

  公开（公告）日：2005-03-10

  The present invention provides compounds of formula (I) including stereoisomers, prodrugs and pharmaceutically acceptable salts or solvates thereof wherein R is aryl or heteroaryl and each of the above groups R may be substituted by 1 to 4 groups selected from: halogen, C1-C6 alkyl, C1-C6 alkoxy, halo C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halo C1-C6 alkoxy, —COR 4 , nitro, —NR 3 R 4 cyano, or a group R 5 ; R 1 is hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halo C1-C6 alkyl, halo C1-C6 alkoxy, halogen, NR 3 R 4 or cyano; R 2 corresponds to a group CHR 6 R 7 ; R 3 is hydrogen, C1-C6 alkyl; R 4 independently from R 3 , has the same meanings; R 5 is C3-C7 cycloalkyl, which may contain one or more double bonds; aryl; or a 5-6 membered heterocycle; wherein each of the above groups R 5 may be substituted by one or more groups selected from: halogen, C1-C6 alkyl, C1-C6 alkoxy, halo C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halo C1-C6 alkoxy, C1-C6 dialkylamino, nitro or cyano; R 6 is hydrogen, C2-C6 alkenyl or C1-C6 alkyl, wherein each of the above groups R6 may be substituted by one or more groups selected from: C1-C6 alkoxy and hydroxy; R 7 independently from R 6 , has the same meanings; X is carbon or nitrogen; to processes for their preparation, to pharmaceutical compositions containing them and to their use in the treatment of conditions mediated by corticotropin-releasing factor (CRF).

  本发明提供了式（I）的化合物，包括立体异构体、前药和其药学上可接受的盐或溶剂，其中R为芳基或杂环芳基，上述每个R基团都可以被1至4个选自以下基团的基团所取代：卤素，C1-C6烷基，C1-C6烷氧基，卤代C1-C6烷基，C2-C6烯基，C2-C6炔基，卤代C1-C6烷氧基，-COR4，硝基，-NR3R4氰基或R5基团；其中，R1为氢，C1-C6烷基，C2-C6烯基，C2-C6炔基，卤代C1-C6烷基，卤代C1-C6烷氧基，卤素，NR3R4或氰基；R2对应于一个基团CHR6R7；R3为氢，C1-C6烷基；R4独立于R3，具有相同的含义；R5为C3-C7环烷基，其中可以含有一个或多个双键；芳基；或5-6成员杂环；其中上述每个R5基团都可以被一个或多个选自以下基团的基团所取代：卤素，C1-C6烷基，C1-C6烷氧基，卤代C1-C6烷基，C2-C6烯基，C2-C6炔基，卤代C1-C6烷氧基，C1-C6二烷基氨基，硝基或氰基；R6为氢，C2-C6烯基或C1-C6烷基，其中上述每个R6基团都可以被一个或多个选自以下基团的基团所取代：C1-C6烷氧基和羟基；R7独立于R6，具有相同的含义；X为碳或氮；本发明还提供了制备这些化合物的方法，包含它们的制药组合物以及它们在治疗由促肾上腺皮质激素释放因子（CRF）介导的疾病中的用途。
• Fused pyrimidines as antagonists of the corticotropin releasing factor (crf)
  申请人：——

  公开号：US20040176400A1

  公开（公告）日：2004-09-09

  The present invention provides compounds of formula (I) including stereoisomers, prodrugs and pharmaceutically acceptable salts or solvates thereof wherein the variables are as defined in the description, processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of conditions mediated by corticotropin-releasing factor (CRF). 1

  本发明提供了公式（I）的化合物，包括立体异构体、前药和其药学上可接受的盐或溶剂，其中变量如描述中所定义，以及其制备过程、含有它们的制药组合物以及它们在治疗由促肾上腺皮质激素释放因子（CRF）介导的疾病方面的用途。
• Condensed n-heterocyclic compounds and their use as crf receptor antagonists
  申请人：St-Denis Yves

  公开号：US20070021429A1

  公开（公告）日：2007-01-25

  The present invention provides compounds of formula (I) including stereoisomers, prodrugs and pharmaceutically acceptable salts or solvates thereof (Formula (I)) wherein the dashed line may represent a double bond; R is aryl or heteroaryl, each of which may be substituted by 1 to 4 groups J selected from: halogen, C1-C6 alkyl, C1-C6 alkoxy, halo C1-C6 alkyl, C2-C6 .alkenyl, ,C2-C6 alkynyl, halo C1=C6 alkoxy, =C(O)RZ, nitro, hydroxy, =NR3R4i cyano, and or a group Z; R, is hydrogen, C3-C7 cycloalkyl, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 thioalkyl, C2-C6 alkenyl, C2-C6 alkynyl, halo C1-C6 alkyl, halo C1-C6 alkoxy, halogen, NR 3 R 4 or cyano; D, G R is —C— optionally substituted; A is —C— optionally substituted; X is carbon or nitrogen; Y is nitrogen or —C— optionally substituted; W is a 4-8 carbocyclic membered ring, which may be saturated or may contain one to three double bonds, and inwhich: —one carbon atom is replaced by a carbonyl or S(O) m ; and —one to four carbon atoms may optionally be replaced by oxygen, nitrogen or NR 14 , S(O) m , carbonyl, and such ring may be further substituted by I to 8 substituents; Z is a 5-6 membered heterocycle or a phenyl, which may be substituted by I to 8 substituents; m is an integer from 0 to 2, to processes for their preparation, to pharmaceutical compositions containing them and to their use in the treatment of conditions mediated by corticotropin-releasing factor (CRF).

  本发明提供了式(I)的化合物，包括立体异构体、前药和其药学上可接受的盐或溶剂化物（式(I)）其中虚线可以表示双键; R是芳基或杂环芳基，每个都可以被1到4个J基团取代，所选基团包括：卤素、C1-C6烷基、C1-C6烷氧基、卤代C1-C6烷基、C2-C6烯基、C2-C6炔基、卤代C1=C6烷氧基、=C(O)RZ、硝基、羟基、=NR3R4i氰基或Z基；R'是氢、C3-C7环烷基、C1-C6烷基、C1-C6烷氧基、C1-C6硫代烷基、C2-C6烯基、C2-C6炔基、卤代C1-C6烷基、卤代C1-C6烷氧基、卤素、NR3R4或氰基；D、G和R是—C—可选取代；A是—C—可选取代；X是碳或氮；Y是氮或—C—可选取代；W是4-8个碳环状成员环，可以饱和或含有1至3个双键，其中：—一个碳原子被羰基或S(O)m取代；—1至4个碳原子可以选择性地被氧、氮或NR14、S(O)m、羰基取代，此环可以进一步被1至8个取代基团取代；Z是5-6个成员的杂环或苯基，可以被1至8个取代基团取代；m是从0到2的整数，以及其制备过程、含有它们的制药组合物以及它们在治疗通过促肾上腺皮质激素释放因子（CRF）介导的疾病中的应用。
• CRF RECEPTOR ANTAGONISTS AND METHODS RELATING THERETO
  申请人：Neurocrine Biosciences, Inc.

  公开号：EP1129091A2

  公开（公告）日：2001-09-05