3-乙酰基-4-异丙氧基苯甲酸甲酯 | 259147-67-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 3-乙酰基-4-异丙氧基苯甲酸甲酯
• 英文名称: 3-acetyl-4-(1-methylethoxy)-methyl-benzoate
• 英文别名: methyl 3-acetyl-4-(1-methylethoxy)-methyl-benzoate；Methyl 3-Acetyl-4-iso-propoxybenzoate；Methyl 3-acetyl-4-isopropoxybenzoate；methyl 3-acetyl-4-propan-2-yloxybenzoate
• CAS: 259147-67-6
• 化学式: C₁₃H₁₆O₄
• 分子量: 236.268
• InChiKey: ZOGPYKAGBMBZAW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-乙酰基-4-异丙氧基苯甲酸甲酯 、 7-amino-5,8-dichlorotetrahydroisoquinoline 在 sodium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以83%的产率得到3-acetyl-N-(5,8-dichloro-1,2,3,4-tetrahydro-7-isoquinolinyl)-4-(1-methylethoxy)benzamide
  参考文献：
  名称：

  The Development of a New Manufacturing Route to the Novel Anticonvulsant, SB-406725A

  摘要：

  The development of an efficient manufacturing route to 3-acetyl-N-(5,8-dichloro-1,2,3,4-tetrahydro-7-isoquinolinyl)-4-(1-methylethyoxy)-benzamide hydrochloride SB-406725A (1) is described. Title synthesis begins with dichlorination of isoquinoline, followed by nitration using nitronium tetrafluoroborate in sulpholane. Nitroisoquinoline (12) was hydrogenated under pressure using Pt/C. The resultant tetrahydroisoquinoline (13) was selectively coupled with benzoate side chain (15) under base-promoted conditions using sodium hexamethyldisilazane to yield the parent molecule SB406725 (16). SB-406725 was then converted to the HCl salt SB-406725A (1). This process has been successfully demonstrated on a pilot-plant scale to prepare similar to 30 kg of SB-406725A (1).

  DOI：

  10.1021/op9002054

文献信息

• SUBSTITUTED ISOQUINOLINE DERIVATIVES AND THEIR USE AS ANTICONVULSANTS
  申请人：SMITHKLINE BEECHAM PLC

  公开号：EP1042296A1

  公开（公告）日：2000-10-11
• US6248754B1
  申请人：——

  公开号：US6248754B1

  公开（公告）日：2001-06-19
• US6492378B1
  申请人：——

  公开号：US6492378B1

  公开（公告）日：2002-12-10
• [EN] SUBSTITUTED ISOQUINOLINE DERIVATIVES AND THEIR USE AS ANTICONVULSANTS<br/>[FR] DERIVES D'ISOQUINOLINE SUBSTITUEE ET UTILISATION DE CES DERNIERS COMME ANTICONVULSIFS
  申请人：SMITHKLINE BEECHAM PLC

  公开号：WO1999031068A1

  公开（公告）日：1999-06-24

  (EN) Compounds of formula (I) or pharmaceutically acceptable salts or solvates thereof, where Q is a monocyclic or bicyclic aryl or heteroaryl ring, R1 is hydrogen, C1-6alkyl (optionally substituted by hydroxy or C1-4alkoxy), C1-6alkenyl, C1-6alkynyl, C1-6alkylCO-, formyl, CF3CO- or C1-6alkylSO2-, R2 is hydrogen or up to three substituents selected from halogen, NO2, CN, N3, CF3O-, CF3S-, CF3CO-, trifluoromethyldiazirinyl, C1-6alkyl, C1-6alkenyl, C1-6alkynyl, C1-6perfluoroalkyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-4alkyl-, C1-6alkylO-, C1-6alkylCO-, C3-6cycloalkylO-, C3-6cycloalkylCO-, C3-6cycloalkyl-C1-4alkylO-, C3-6cycloalkyl-C1-4alkylCO-, phenyl, phenoxy, benzyloxy, benzoyl, phenyl-C1-4alkyl-, C1-6alkylS-, C1-6alkylSO2-, (C1-4alkyl)2NSO2-, (C1-4alkyl)NHSO2-, (C1-4alkyl)2NCO-, (C1-4alkyl)NHCO, CONH2, CF3SO2, C1-6alkenyl, C1-6alkynyl or C1-6hydroxyalkyl; or -NR3R4 where R3 is hydrogen or C1-4alkyl, and R4 is hydrogen, C1-4alkyl, formyl, -CO2C1-4alkyl or -COC1-4alkyl; or two R2 groups together form a carbocyclic ring that is saturated or unsaturated and unsubstituted or substituted by -OH or =O; and X is halogen, C1-6alkoxy, C1-6alkyl, C2-6alkenyl optionally substituted by phenyl; are useful in the treatment and/or prophylaxis of anxiety, mania, depression, panic disorders and/or aggression, disorders associated with a subarachnoid haemorrhage or neural shock, the effects associated with withdrawal from substances of abuse such as cocaine, nicotine, alcohol and benzodiazepines, disorders treatable and/or preventable with anti-convulsive agents, such as epilepsy including post-traumatic epilepsy, Parkinson's disease, psychosis, migraine, cerebral ischaemia, Alzheimer's disease and other degenerative diseases such as Huntingdon's chorea, schizophrenia, obsessive compulsive disorders (OCD), neurological deficits associated with AIDS, sleep disorders (including circadian rhythm disorders, insomnia and narcolepsy), tics (e.g. Giles de la Tourette's syndrome), traumatic brain injury, tinnitus, neuralgia, especially trigeminal neuralgia, neuropathic pain, dental pain, cancer pain, inappropriate neuronal activity resulting in neurodysthesias in diseases such as diabetes, multiple sclerosis (MS) and motor neurone disease, ataxias, muscular rigidity (spasticity), temporomandibular joint dysfunction, or amyotrophic lateral sclerosis (ALS).(FR) L'invention concerne des composés selon la formule (I) ou des sels pharmaceutiquement acceptables ou des solvates de ces derniers. Dans la formule (I) Q représente un aryle monocyclique ou bicyclique ou une chaîne hétéroaryle, R1 représente hydrogène, C1-6alkyle (éventuellement substitué par hydroxy ou C1-4 alcoxy), C1-6alkényle, C1-6alkynyle, C1-6alkylCO-, formyle, CF3CO- ou C1-6alkylSO2-, R2 représente hydrogène ou jusqu'à trois substituant sélectionnés parmi halogène, NO2, CN, N3, CF3O-, CF3S-,CF3CO-, trifluorométhyldiazirinyle, C1-6alkyle, C1-6alkényle, C1-6alkynyle, C1-6perfluoroalkyle, C3-6cycloalkyle, C3-6cycloalkyle-C1-4alkyle-, C1-6alkylO-, C1-6alkylCO-, C3-6cycloalkylO-, C3-6cycloalkylCO-, C3-6cycloalkyl-C1-4alkylO-, C3-6cycloalkyle-C1-4alkyleCO-, phényle, phénoxy, benzyloxy, benzoyl, phényle-C1-4alkyle-, C1-6alkylS-, C1-6alkylSO2-, (C1-4alkyl)2NSO2-, (C1-4alkyl)NHSO2-, (C1-4alkyl)2NCO-, (C1-4alkyl)NHCO, CONH2, CF3SO2, C1-6alkényle, C1-6alkynyle ou C1-6hydroxyalkyle; ou -NR3R4 où R3 représente hydrogène ou C1-4alkyle, et R4 représente hydrogène, C1-4alkyle, foryle, -CO2C1-4alkyle ou -COC1-4alkyle; ou deux groupes R2 forment ensemble une chaine carbocyclique qui est saturée ou non saturée et non substituée ou substituée par -OH ou =O; et X représente halogène, C1-6alcoxy, C1-6alkyle, C2-6alkényle éventuellement substitué par phényle. Ces composés présentent une grande utilité dans le traitement et/ou la prophylaxie de l'anxiété, la manie, la dépression, les troubles de panique et/ou d'agression, les troubles associés à une hémorragie sous-arachnoïdienne ou choc neuronal, les effets associés au sevrage de drogues telles que la cocaine, la nicotine, l'alcool et les benzodiazépines, les troubles pouvant être traités et/ou prévenus par des agents anticonvulsifs, comme l'épilepsie post-traumatique, la maladie de Parkison, la psychose, la migraine, l'ischémie cérébrale, la maladie d'Alzheimer, et autres maladies dégénératives comme la chorée de Hundington, la schizophrénie, les troubles obsessionnels compulsifs, les déficits neurologiques associés au SIDA, les troubles du sommeil (y compris les troubles du rythme circadien, l'insomnie et la narcolepsie), les tics (par exemple, syndrome de Giles de la Tourette), les lésions traumatiques du cerveau, les acouphènes, la névralgie, en particulier, la névralgie faciale, les douleurs neuropathiques, les douleurs dentaires, les douleurs du cancer, l'activité neuronale inappropriée se traduisant par une dystasie dans les maladies comme le diabète, la sclérose en plaques et la maladie du motoneurone, l'ataxie, la rigidité musculaire (spasticité), les troubles des articulations temporo-mandibulaires ou la sclérose latérale amyotrophique.
• [EN] SUBSTITUTED ISOQUINOLINE DERIVATIVES AND THEIR USE AS ANTICONVULSIVANTS<br/>[FR] DERIVES D'ISOQUINOLINE SUBSTITUES ET LEUR UTILISATION COMME ANTIEPILEPTIQUES
  申请人：SMITHKLINE BEECHAM PLC

  公开号：WO2000009486A1

  公开（公告）日：2000-02-24

  Compound of formula (I) or salts thereof or solvates thereof: wherein: R1 is hydrogen, C¿1-6?alkyl (optionally substituted by hydroxy or C1-4alkoxy), C1-6alkenyl, C1-6alkynyl, C1-6alkylCO-, formyl, CF3CO-or C1-6alkylSO2-: R?2¿ is hydrogen or up to three substituents selected from halogen, NO¿2?, CN, N3, CF3O-, CF3S-, CF3CO-, CF3SO2, trifluoromethyldiazirinyl, C1-6alkyl, C1-6alkenyl, C1-6alkynyl, C1-6perfluoroalkyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-4alkyl-, C1-6alkylO-, C1-6alkylCO-, C3-6cycloalkylO-, C3-6cycloalkylCO-, C3-6cycloalkyl-C1-4alkylO-, C3-6cycloalkyl-C1-4alkylCO-, phenyl, phenoxy, benzyloxy, benzoyl, phenyl-C1-4alkyl-, C1-6alkylS-, C1-6alkylSO2-, (C1-4alkyl)2NSO2-, (C1-4alkyl)NHSO2-, (C1-4)2NCO-, (C1-4alkyl)NHCO- and CONH2; or -NR?5R6¿ where R5 is hydrogen or C¿1-4?alkyl, and R?6¿ is hydrogen, C¿1-4?alkyl, formyl, -CO2C1-4alkyl or -COC1-4alkyl; or two R?2¿ groups together form a carbocyclic ring that is saturated or unsaturated and unsubstituted or substituted by -OH or =O; the two R groups, the two R3 groups and the two R4 groups are each independently hydrogen, C¿1-6?alkyl, C1-6alkenyl, benzyl, or phenyl, or the two R groups and/or the two R?3¿ groups and/or the two R4 groups together form a C¿3-6?spiroalkyl group, provided that at least one R, R?3 or R4¿ group is other than hydrogen; and X is selected from the group consisting of hydrogen, halogen, cyano, CF¿3?, alkyl and alkoxy; provided that when X is hydrogen, the two R groups are not both hydrogen are indicated to be useful in the treatment and prophylaxis of epilepsy, migraine, and other disorders.