4-[[5-bromo-4-(4-cyano-2,6-dimethylphenoxy)-6-methyl-2-pyrimidinyl]amino]benzonitrile | 269055-44-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-[[5-bromo-4-(4-cyano-2,6-dimethylphenoxy)-6-methyl-2-pyrimidinyl]amino]benzonitrile
• 英文别名: 4-[5-Bromo-2-(4-cyanoanilino)-6-methylpyrimidin-4-yl]oxy-3,5-dimethylbenzonitrile
• CAS: 269055-44-9
• 化学式: C₂₁H₁₆BrN₅O
• 分子量: 434.295
• InChiKey: QQBGELLHYHPCDK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  94.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  N-甲基吡咯烷酮 、 对氨基苯腈 以 水 、 乙腈 为溶剂， 生成 4-[[5-bromo-4-(4-cyano-2,6-dimethylphenoxy)-6-methyl-2-pyrimidinyl]amino]benzonitrile
  参考文献：
  名称：

  HIV REPLICATION INHIBITING PYRIMIDINES

  摘要：

  这项发明涉及使用式1化合物，其N-氧化物，药用可接受的加成盐，季铵盐和其立体化学异构体，其中-a1=-a2-a3=a4-形成苯基，吡啶基，嘧啶基，吡啉基或吡嗪基与附加的乙烯基；n为0至4；如可能为5；R1为氢，芳基，甲酰基，C1-6烷基羰基，C1-6烷基，C1-6烷氧羰基，取代的C1-6烷基，或取代的C1-6烷氧基烷基羰基；每个R2独立地为羟基，卤素，可选地取代的C1-6烷基，C2-6烯基或C2-6炔基，C3-7环烷基，C1-6烷氧基，C1-6烷氧羰基，羧基，氰基，硝基，氨基，单或双(C1-6烷基)氨基，多卤甲基，多卤甲氧基，多卤甲硫基，—S(═O)pR6，—NH—S(═O)pR6，—C(═O)R6，—NHC(═O)H，—C(═O)NHNH2，—NHC(═O)R6，—C(═NH)R6或5-成员杂环环；p为1或2；L为可选地取代的C1-10烷基，C2-10烯基，C2-10炔基或C3-7环烷基；或L为—X—R3，其中R3为可选地取代的苯基，吡啶基，嘧啶基，吡嗪基或吡啉基；X为—NR1—，—NH—NH—，—N═N—，—O—，—C(═O)—，—CHOH—，—S—，—S(═O)—或—S(═O)2—；Q为氢，C1-6烷基，卤素，多卤C1-6烷基或可选地取代的氨基；Y代表羟基，卤素，C3-7环烷基，可选地取代的C1-6烷基，C2-6烯基或C2-6炔基，C1-6烷氧基，C1-6烷氧羰基，羧基，氰基，硝基，氨基，单或双(C1-6烷基)氨基，多卤甲基，多卤甲氧基，多卤甲硫基，—S(═O)pR6，—NH—S(═O)pR6，—C(═O)R6，—NHC(═O)H，—C(═O)NHNH2，—NHC(═O)R6，—C(═NH)R6或芳基；芳基为可选地取代的苯基；Het为可选地取代的杂环基团；用于制造治疗感染艾滋病毒（Human Immunodeficiency Virus）的患者的药物。

  公开号：

  US20030114472A1

文献信息

• PROCESS FOR SYNTHESIS OF DIARYLPYRIMIDINE NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR
  申请人：Gurjar Mukund Keshav

  公开号：US20110196156A1

  公开（公告）日：2011-08-11

  A method for synthesis of diarylpyrimidine non-nucleoside reverse transcriptase inhibitor such as etravirine is provided Typically, etravirine is synthesized by the steps of a Condensing 2,4,6-trichlorpyrimidine with 3,5-dimethyl-4-hydroxybenzonitrile to obtain compound (V), b Condensing compound (V) with 4-aminobenzonitrile to obtain compound (VI), c Ammonolysis of compound (VI) to get compound (IV), d Halogenation of compound (IV) to get etravirine.

  提供了一种合成二芳基嘧啶非核苷类逆转录酶抑制剂（如埃替韦）的方法。通常，埃替韦的合成步骤包括：a 将2,4,6-三氯嘧啶与3,5-二甲基-4-羟基苯甲腈缩合得到化合物（V），b 将化合物（V）与4-氨基苯甲腈缩合得到化合物（VI），c 对化合物（VI）进行氨解得到化合物（IV），d 对化合物（IV）进行卤代反应得到埃替韦。
• HIV REPLICATION INHIBITING PYRIMIDINES
  申请人：——

  公开号：US20030114472A1

  公开（公告）日：2003-06-19

  This invention concerns the use of compounds of formula 1 the N-oxides, the pharmaceutically acceptable addition salts, quaternary amines and the stereochemically isomeric forms thereof, wherein -a 1 =-a 2 -a 3 =a 4 - forms a phenyl, pyridinyl, pyrimidinyl, pyridazinyl or pyrazinyl with the attached vinyl group; n is 0 to 4; and where possible 5; R 1 is hydrogen, aryl, formyl, C 1-6 alkylcarbonyl, C 1-6 alkyl, C 1-6 alkyloxy-carbonyl, substituted C 1-6 alkyl, or substituted C 1-6 alkyloxyC 1-6 alkylcarbonyl; each R 2 independently is hydroxy, halo, optionally substituted C 1-6 alkyl, C 2-6 alkenyl or C 2-6 alkynyl, C 3-7 cycloalkyl, C 1-6 alkyloxy, C 1-6 alkyloxycarbonyl, carboxyl, cyano, nitro, amino, mono- or di(C 1-6 alkyl)amino, polyhalomethyl, polyhalomethyloxy, polyhalo-methylthio, —S(═O) p R 6 , —NH—S(═O) p R 6 , —C(═O)R 6 , —NHC(═O)H, —C(═O)NHNH 2 , —NHC(═O)R 6 , —C(═NH)R 6 or a 5-membered heterocyclic ring; p is 1 or 2; L is optionally substituted C 1-10 alkyl, C 2-10 alkenyl, C 2-10 alkynyl or C 3-7 cycloalkyl; or L is —X—R 3 wherein R 3 is optionally substituted phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl; X is —NR 1 —, —NH—NH—, —N═N—, —O—, —C(═O)—, —CHOH—, —S—, —S(═O)— or —S(═O) 2 —; Q is hydrogen, C 1-6 alkyl, halo, polyhalo-C 1-6 alkyl or an optionally substituted amino group; Y represents hydroxy, halo, C 3-7 cycloalkyl, optionally substituted C 1-6 alkyl, C 2-6 alkenyl or C 2-6 alkynyl, C 1-6 alkyloxy, C 1-6 alkyloxycarbonyl, carboxyl, cyano, nitro, amino, mono- or di(C 1-6 alkyl)amino, polyhalomethyl, polyhalomethyloxy, polyhalomethylthio, —S(═O) p R 6 , —NH—S(═O) p R 6 , —C(═O)R 6 , —NHC(═O)H, —C(═O)NHNH 2 , —NHC(═O)R 6 , —C(═NH)R 6 or aryl; aryl is optionally substituted phenyl; Het is an optionally substituted heterocyclic radical; for the manufacture of a medicine for the treatment of subjects suffering from HIV (Human Immunodeficiency Virus) infection.

  这项发明涉及使用式1化合物，其N-氧化物，药用可接受的加成盐，季铵盐和其立体化学异构体，其中-a1=-a2-a3=a4-形成苯基，吡啶基，嘧啶基，吡啉基或吡嗪基与附加的乙烯基；n为0至4；如可能为5；R1为氢，芳基，甲酰基，C1-6烷基羰基，C1-6烷基，C1-6烷氧羰基，取代的C1-6烷基，或取代的C1-6烷氧基烷基羰基；每个R2独立地为羟基，卤素，可选地取代的C1-6烷基，C2-6烯基或C2-6炔基，C3-7环烷基，C1-6烷氧基，C1-6烷氧羰基，羧基，氰基，硝基，氨基，单或双(C1-6烷基)氨基，多卤甲基，多卤甲氧基，多卤甲硫基，—S(═O)pR6，—NH—S(═O)pR6，—C(═O)R6，—NHC(═O)H，—C(═O)NHNH2，—NHC(═O)R6，—C(═NH)R6或5-成员杂环环；p为1或2；L为可选地取代的C1-10烷基，C2-10烯基，C2-10炔基或C3-7环烷基；或L为—X—R3，其中R3为可选地取代的苯基，吡啶基，嘧啶基，吡嗪基或吡啉基；X为—NR1—，—NH—NH—，—N═N—，—O—，—C(═O)—，—CHOH—，—S—，—S(═O)—或—S(═O)2—；Q为氢，C1-6烷基，卤素，多卤C1-6烷基或可选地取代的氨基；Y代表羟基，卤素，C3-7环烷基，可选地取代的C1-6烷基，C2-6烯基或C2-6炔基，C1-6烷氧基，C1-6烷氧羰基，羧基，氰基，硝基，氨基，单或双(C1-6烷基)氨基，多卤甲基，多卤甲氧基，多卤甲硫基，—S(═O)pR6，—NH—S(═O)pR6，—C(═O)R6，—NHC(═O)H，—C(═O)NHNH2，—NHC(═O)R6，—C(═NH)R6或芳基；芳基为可选地取代的苯基；Het为可选地取代的杂环基团；用于制造治疗感染艾滋病毒（Human Immunodeficiency Virus）的患者的药物。
• [EN] HIV REPLICATION INHIBITING PYRIMIDINES<br/>[FR] PYRIMIDINES INHIBANT LA REPLICATION DU VIH
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2000027825A1

  公开（公告）日：2000-05-18

  This invention concerns the use of compounds of formula (I), the N-oxides, the pharmaceutically acceptable addition salts, quaternary amines and the stereochemically isomeric forms thereof, wherein -a?1=a2=a3=a4¿- forms a phenyl, pyridinyl, pyrimidinyl, pyridazinyl or pyrazinyl with the attached vinyl group; n is 0 to 4; and where possible 5; R1 is hydrogen, aryl, formyl, C¿1-6?alkylcarbonyl, C1-6alkyl, C1-6alkyloxycarbonyl, substituted C1-6alkyl, or substituted C1-6alkyloxyC1-6alkylcarbonyl; each R?2¿ independently is hydroxy, halo, optionally substituted C¿1-6?alkyl, C2-6alkenyl or C2-6alkynyl, C3-7cycloalkyl, C1-6alkyloxy, C1-6alkyloxycarbonyl, carboxyl, cyano, nitro, amino, mono- or di(C1-6alkyl)amino, polyhalomethyl, polyhalomethyloxy, polyhalomethylthio, -S(=O)pR?6¿, -NH-S(=O)¿pR?6, -C(=O)R6, -NHC(=O)H, -C(=O)NHNH¿2?, -NHC(=O)R?6¿, -C(=NH)R6 or a 5-membered heterocyclic ring; p is 1 or 2; L is optionally substituted C¿1-10?alkyl, C2-10alkenyl, C2-10alkynyl or C3-7cycloalkyl; or L is -X-R?3¿ wherein R3 is optionally substituted phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl; X is -NR1-, -NH-NH-, -N=N-, -O-, -C(=O)-, -CHOH-, -S-, -S(=O)- or -S(=O)¿2?-; Q is hydrogen, C1-6alkyl, halo, polyhalo-C1-6alkyl or an optionally substituted amino group; Y represents hydroxy, halo, C3-7cycloalkyl, optionally substituted C1-6alkyl, C2-6alkenyl or C2-6alkynyl, C1-6alkyloxy, C1-6alkyloxycarbonyl, carboxyl, cyano, nitro, amino, mono- or di(C1-6alkyl)amino, polyhalomethyl, polyhalomethyloxy, polyhalomethylthio, -S(=O)pR?6¿, -NH-S(=O)¿pR?6, -C(=O)R6, -NHC(=O)H, -C(=O)NHNH¿2?, -NHC(=O)R?6¿, -C(=NH)R6 or aryl; aryl is optionally substituted phenyl; Het is an optionally substituted heterocyclic radical; for the manufacture of a medicine for the treatment of subjects suffering from HIV (Human Immunodeficiency Virus) infection.

  本发明涉及使用式(I)化合物，其N-氧化物、药学上可接受的加成盐、季铵盐及其立体化学异构体，其中-a?1=a2=a3=a4¿-形成一个苯基、吡啶基、嘧啶基、吡嗪基或吡唑基，并与附加的乙烯基结合；n为0至4，如可能为5；R1为氢、芳基、甲酰基、C¿1-6?烷基羰基、C1-6烷基、C1-6烷氧羰基、取代C1-6烷基或取代C1-6烷氧基C1-6烷基羰基；每个R?2¿独立地为羟基、卤素、可选取代的C¿1-6?烷基、C2-6烯基或C2-6炔基、C3-7环烷基、C1-6烷氧基、C1-6烷氧羰基、羧基、氰基、硝基、氨基、单烷基或双(C1-6烷基)氨基、多卤甲基、多卤甲氧基、多卤甲硫基、-S(=O)pR?6¿、-NH-S(=O)¿pR?6、-C(=O)R6、-NHC(=O)H、-C(=O)NHNH¿2?、-NHC(=O)R?6¿、-C(=NH)R6或5-成员杂环环；p为1或2；L为可选取代的C¿1-10?烷基、C2-10烯基、C2-10炔基或C3-7环烷基；或L为-X-R?3¿，其中R3为可选取代的苯基、吡啶基、嘧啶基、吡嗪基或吡唑基；X为-NR1-、-NH-NH-、-N=N-、-O-、-C(=O)-、-CHOH-、-S-、-S(=O)-或-S(=O)¿2?-；Q为氢、C1-6烷基、卤素、多卤代C1-6烷基或可选取代的氨基；Y代表羟基、卤素、C3-7环烷基、可选取代的C1-6烷基、C2-6烯基或C2-6炔基、C1-6烷氧基、C1-6烷氧羰基、羧基、氰基、硝基、氨基、单烷基或双(C1-6烷基)氨基、多卤甲基、多卤甲氧基、多卤甲硫基、-S(=O)pR?6¿、-NH-S(=O)¿pR?6、-C(=O)R6、-NHC(=O)H、-C(=O)NHNH¿2?、-NHC(=O)R?6¿、-C(=NH)R6或芳基；芳基为可选取代的苯基；Het为可选取代的杂环基团；用于制造治疗HIV（人类免疫缺陷病毒）感染患者的药物。
• HIV replication inhibiting pyrimidines
  申请人：De Corte Bart

  公开号：US20050288278A1

  公开（公告）日：2005-12-29

  This invention concerns the use of compounds of formula the N-oxides, the pharmaceutically acceptable addition salts, quaternary amines and the stereochemically isomeric forms thereof, wherein -a 1 =a 2 -a 3 =a 4 - forms a phenyl, pyridinyl, pyrimidinyl, pyridazinyl or pyrazinyl with the attached vinyl group; n is 0 to 4; and where possible 5; R 1 is hydrogen, aryl, formyl, C 1-6 alkylcarbonyl, C 1-6 alkyl, C 1-6 alkyloxy-carbonyl, substituted C 1-6 alkyl, or substituted C 1-6 alkyloxyC 1-6 alkylcarbonyl; each R 2 independently is hydroxy, halo, optionally substituted C 1-6 alkyl, C 2-6 alkenyl or C 2-6 alkynyl, C 3-7 cycloalkyl, C 1-6 alkyloxy, C 1-6 alkyloxycarbonyl, carboxyl, cyano, nitro, amino, mono- or di(C 1-6 alkyl)amino, polyhalomethyl, polyhalomethyloxy, polyhalo-methylthio, —S(═O) p R 6 , —NH—S(═O) p R 6 , —C(═O)R 6 , —NHC(═O)H, —C(═O)NHNH 2 , —NHC(═O)R 6 , —C(═NH)R 6 or a 5-membered heterocyclic ring; p is 1 or 2; L is optionally substituted C 1-10 alkyl, C 2-10 alkenyl, C 2-10 alkynyl or C 3-7 cycloalkyl; or L is —X—R 3 wherein R 3 is optionally substituted phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl; X is —NR 1 —, —NH—NH—, —N═N—, —O—, —C(═O)—, —CHOH—, —S—, —S(═O)— or —S(═O)2—; Q is hydrogen, C 1-6 alkyl, halo, polyhalo-C 1-6 alkyl or an optionally substituted amino group; Y represents hydroxy, halo, C 3-7 cycloalkyl, optionally substituted C 1-6 alkyl, C 2-6 alkenyl or C 2-6 alkynyl, C 1-6 alkyloxy, C 1-6 alkyloxycarbonyl, carboxyl, cyano, nitro, amino, mono- or di(C 1-6 alkyl)amino, polyhalomethyl, polyhalomethyloxy, polyhalomethylthio, —S(═O) p R 6 , —NH—S(═O) p R 6 , —C(═O)R 6 , —NHC(═O)H, —C(═O)NHNH 2 , —NHC(═O)R 6 , —C(═NH)R 6 or aryl; aryl is optionally substituted phenyl. Het is an optionally substituted heterocyclic radical; for the manufacture of a medicine for the treatment of subjects suffering from HIV (Human Immunodeficiency Virus) infection.

  本发明涉及使用式N-氧化物化合物，其药学上可接受的加合物盐、季铵盐及其立体化学异构体，其中-a1=a2-a3=a4-形成带有附加乙烯基的苯基、吡啶基、嘧啶基、吡嗪基或吡唑基；n为0至4，如有可能为5；R1是氢、芳基、甲酰基、C1-6烷基羰基、C1-6烷基、C1-6烷氧基羰基、取代的C1-6烷基或取代的C1-6烷氧基C1-6烷基羰基；每个R2独立地是羟基、卤素、可选取代的C1-6烷基、C2-6烯基或C2-6炔基、C3-7环烷基、C1-6烷氧基、C1-6烷氧羰基、羧基、氰基、硝基、氨基、单烷基或二烷基氨基、多卤甲基、多卤甲氧基、多卤甲硫基、-S(═O)pR6、-NH-S(═O)pR6、-C(═O)R6、-NHC(═O)H、-C(═O)NHNH2、-NHC(═O)R6、-C(═NH)R6或5-成员杂环环；p为1或2；L是可选取代的C1-10烷基、C2-10烯基、C2-10炔基或C3-7环烷基；或L是-X-R3，其中R3是可选取代的苯基、吡啶基、嘧啶基、吡嗪基或吡唑基；X是-NR1-、-NH-NH-、-N═N-、-O-、-C(═O)-、-CHOH-、-S-、-S(═O)-或-S(═O)2-；Q是氢、C1-6烷基、卤素、多卤基C1-6烷基或可选取代的氨基基团；Y代表羟基、卤素、C3-7环烷基、可选取代的C1-6烷基、C2-6烯基或C2-6炔基、C1-6烷氧基、C1-6烷氧羰基、羧基、氰基、硝基、氨基、单烷基或二烷基氨基、多卤甲基、多卤甲氧基、多卤甲硫基、-S(═O)pR6、-NH-S(═O)pR6、-C(═O)R6、-NHC(═O)H、-C(═O)NHNH2、-NHC(═O)R6、-C(═NH)R6或芳基；芳基是可选取代的苯基。Het是可选取代的杂环基；用于制造治疗HIV（人类免疫缺陷病毒）感染患者的药物。
• Antiviral compositions
  申请人：Verreck Geert

  公开号：US20060127487A1

  公开（公告）日：2006-06-15

  The present invention is concerned with pharmaceutical compositions of antiviral compounds which can be administered to a mammal, in particular a human, suffering from a viral infection. These compositions comprise particles obtainable by melt-extruding a mixture comprising one or more antiviral compounds and one or more appropriate water-soluble polymers and subsequently milling said melt-extruded mixture.

  本发明涉及药物组合物，包括抗病毒化合物，可用于治疗哺乳动物，尤其是人类，患有病毒感染。这些组合物包括通过熔融挤出混合物制备的颗粒，该混合物包括一种或多种抗病毒化合物和一种或多种适当的水溶性聚合物，并随后对该熔融挤出的混合物进行磨碎。