1-[N-(2-(3,4-dimethoxy-phenyl)-ethyl)-amino]-3-amino-propane | 55982-98-4

• 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: 1-[N-(2-(3,4-dimethoxy-phenyl)-ethyl)-amino]-3-amino-propane
• 英文别名: 1-[2-(3,4-dimethoxy-phenyl)-ethylamino]-3-amino-propane；3-[2-(3,4-dimethoxy-phenyl)-ethylamino]-propylamine；N1-[2-(3,4-Dimethoxyphenyl)ethyl]-1,3-propanediamine；N'-[2-(3,4-dimethoxyphenyl)ethyl]propane-1,3-diamine
• CAS: 55982-98-4
• 化学式: C₁₃H₂₂N₂O₂
• 分子量: 238.33
• InChiKey: ZLPVHRHKOAFZMH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  17
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  56.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-[N-(2-(3,4-dimethoxy-phenyl)-ethyl)-amino]-3-amino-propane 生成 1-[4,4-Dimethyl-6,7-dimethoxy-1,3-dioxo-(2H,4H)-isoquinolin-2-yl]-3-[2-(3,4-dimethoxy-phenyl)-ethylamino]-propane
  参考文献：
  名称：

  1,3-Dioxo-2-aminoalkyl-4,4-dimethyl-isoquinolines and salts thereof

  摘要：

  式##SPC1##的化合物，其中R.sub.1是氢、卤素、甲氧基或甲硫基，R.sub.2是氢或甲氧基，n为2或3，A为##SPC2##或##SPC3##其中R.sub.3为氢或甲基，R.sub.4为吡啶基、甲基吡啶基、苯基、氯苯基、三氟甲基苯基、甲苯基、二甲苯基、乙基苯基、二乙基苯基、甲氧基苯基或二甲氧基苯基，R.sub.5和R.sub.6可相同也可不同，均为氢或甲氧基，以及其非毒性、药理学上可接受的酸盐；这些化合物及其盐可用作降压药、镇静剂、抗心律失常药和缓慢心率药。

  公开号：

  US03948898A1
• 作为产物：
  描述：

  3-[(3,4-二甲氧基苯乙基)氨基]丙腈 生成 1-[N-(2-(3,4-dimethoxy-phenyl)-ethyl)-amino]-3-amino-propane
  参考文献：
  名称：

  KUTTER, E.;EBERLEIN, W.;AUSTEL, V.;HEIDER, J.

  摘要：

  DOI：

文献信息

• 1,3-Dioxo-2-[(methoxyphenethyl-amino)-alkyl]-4,4-dimethyl-isoquinolines
  申请人：Boehringer Ingelheim GmbH

  公开号：US04021558A1

  公开（公告）日：1977-05-03

  Compounds of the formula ##STR1## wherein R.sub.1 is hydrogen, halogen, methoxy or methylthio, R.sub.2 is hydrogen or methoxy, n is 2 or 3, R.sub.3 is hydrogen or methyl, and R.sub.4 and R.sub.5, which may be identical to or different from each other, are each hydrogen or methoxy, and non-toxic, pharmacologically acceptable acid addition salts thereof; the compounds as well as the salts are useful as hypotensives, sedatives, antiarrhythmics and bradycardiacs.

  式为##STR1##的化合物，其中R.sub.1是氢、卤素、甲氧基或甲硫基，R.sub.2是氢或甲氧基，n为2或3，R.sub.3是氢或甲基，R.sub.4和R.sub.5，它们可能相同也可能不同，分别是氢或甲氧基，以及其非毒性、药理学上可接受的酸盐；这些化合物以及盐可用作降压药、镇静剂、抗心律失常药和心动过缓药。
• Phenylalkylamino-alkyl derivatives of quinazolinone and phthalazinone
  申请人：Boehringer Ingelheim GmbH

  公开号：US04134980A1

  公开（公告）日：1979-01-16

  Compounds of the formula ##STR1## wherein A is ##STR2## where R.sub.1 is hydrogen or alkyl of 1 to 3 carbon atoms; R.sub.2 is alkoxy of 1 to 3 carbon atoms; R.sub.3 is alkoxy of 1 to 3 carbon atoms or, together with R.sub.2, methylenedioxy or ethylenedioxy; R.sub.4 is hydrogen, alkyl of 1 to 3 carbon atoms or benzyl; R.sub.5 is hydrogen or alkyl of 1 to 3 carbon atoms; R.sub.6 is hydrogen or alkoxy of 1 to 3 carbon atoms; R.sub.7 is alkoxy of 1 to 3 carbon atoms or, together with R.sub.6, methylenedioxy or ethylenedioxy; and N is 2 or 3; And non-toxic, pharmacologically acceptable acid addition salts thereof; the compounds as well as their salts are useful as heart rate reducers and mild antihypertensives. This invention relates to novel N-(phenylalkylaminoalkyl)-substituted quinazolinones and phthalazinones and nontoxic acid addition salts thereof, as well as to various methods of preparing these compounds. More particularly, the present invention relates to a novel class of N-substituted quinazolinones and phthalazinones represented by the formula ##STR3## wherein A is ##STR4## where R.sub.1 is hydrogen or alkyl of 1 to 3 carbon atoms; R.sub.2 is alkoxy of 1 to 3 carbon atoms; R.sub.3 is alkoxy of 1 to 3 carbon atoms or, together with R.sub.2, methylenedioxy or ethylenedioxy; R.sub.4 is hydrogen, alkyl of 1 to 3 carbon atoms or benzyl; R.sub.5 is hydrogen or alkyl of 1 to 3 carbon atoms; R.sub.6 is hydrogen or alkoxy of 1 to 3 carbon atoms; R.sub.7 is alkoxy of 1 to 3 carbon atoms or, together with R.sub.6, methylenedioxy or ethylenedioxy; and N is 2 or 3; Or a non-toxic, pharmacologically acceptable acid addition salt thereof. A preferred sub-genus thereunder is constituted by compounds of the formula I where R.sub.1 and R.sub.5 are each hydrogen, methyl, ethyl, n-propyl or isopropyl; R.sub.4 is hydrogen, methyl, ethyl, n-propyl, isopropyl or benzyl; R.sub.2, r.sub.3 and R.sub.7 are each methoxy, ethoxy, n-propoxy or isopropoxy; R.sub.6 is hydrogen, methoxy, ethoxy, n-propoxy or isopropoxy; R.sub.2 and R.sub.3, together with each other, are methylenedioxy or ethylenedioxy; R.sub.6 and R.sub.7, together with each other, are methylenedioxy or ethylenedioxy; and n is 2 or 3; and non-toxic, pharmacologically acceptable acid addition salts thereof. A further, especially preferred sub-genus thereunder is constituted by compounds of the formula I where R.sub.2 and R.sub.3 are methoxy in the 6- and 7-position, respectively, or, together with each other, methylenedioxy or ethylenedioxy; R.sub.4 is hydrogen or methyl; R.sub.5 is hydrogen; R.sub.6 is hydrogen or methoxy in the 3-position; R.sub.7 is methoxy in the 4-position or, together with R.sub.6, methylenedioxy or ethylenedioxy; and n is 2 or 3; and non-toxic, pharmacologically acceptable acid addition salts thereof. The compounds embraced by formula I may be prepared by the following methods: Method A By reacting a compound of the formula ##STR5## wherein R.sub.2, R.sub.3, A and n have the same meanings as in formula I, and Z is a leaving-group, such as chlorine, bromine, iodine, alkylsulfonyloxy or arylsulfonyloxy, with a phenylalkylamine of the formula ##STR6## wherein R.sub.4, R.sub.5, R.sub.6 and R.sub.7 have the same meanings as in formula I. The reaction is carried out in an inert solvent, such as ether, tetrahydrofuran, methylformamide, dimethylformamide, dimethylsulfoxide, chlorobenzene or benzene, and depending upon the reactivity of substituent Z, at a temperature between -50 and +250.degree. C, but preferably at the boiling point of the particular solvent which is used. The presence of an acid-binding agent, such as an alkali metal alcoholate, an alkali metal hydroxide, an alkali metal carbonate, especially potassium carbonate, or a tertiary organic base, particularly triethylamine or pyridine, or of a reaction accelerator, such as potassium iodide, is of advantage. Method B By reacting a compound of the formula ##STR7## wherein A, R.sub.2 and R.sub.3 have the same meanings as in formula I, with a phenylalkylamine of the formula ##STR8## wherein R.sub.4, R.sub.5, R.sub.6 and n have the same meanings as in formula I, and Z has the same meanings as in formula II. The reaction is carried out in an inert solvent, such as acetone, dimethylformamide, dimethylsulfoxide or chlorobenzene, and, depending upon the reactivity of substituent Z, at a temperature between 0 and 150.degree. C, but preferably at the boiling point of the particular solvent which is used. The presence of an acid-binding agent, such as an alkali metal alcoholate, an alkali metal hydroxide, an alkali metal carbonate, especially potassium carbonate, an alkali metal amide or a tertiary organic base, particularly triethylamine or pyridine, or of a reaction accelerator, such as potassium iodide, is of advantage. Method C By reacting an aldehyde of the formula ##STR9## wherein R.sub.2, R.sub.3, A and n have the same meanings as in formula I, or an acetal thereof, with an amine of the formula III in the presence of catalytically activated hydrogen. The reductive amination is carried out with hydrogen in the presence of a hydrogenation catalyst, such as palladized charcoal, at a hydrogen pressure of 5 atmospheres, in a solvent, such as methanol, ethanol or dioxane, and at a temperature between 0 and 100.degree. C, but preferably between 20 and 80.degree. C. Method D By reacting an amine of the formula ##STR10## wherein R.sub.2, R.sub.3, R.sub.4, A and n have the same meanings as in formula I, with a phenylalkyl compound of the formula ##STR11## wherein R.sub.5, R.sub.6 and R.sub.7 have the same meanings as in formula I, and Z has the same meanings as in formula II. The reaction is carried out in an inert solvent, such as acetone, methylene chloride, dimethylformamide, dimethylsulfoxide or chlorobenzene, and, depending upon the reactivity of substituent Z, at a temperature between 0 and 150.degree. C, but preferably at the boiling point of the particular solvent which is used. The presence of an acid-binding agent, such as an alkali metal alcoholate, an alkali metal hydroxide, an alkali metal carbonate, especially potassium carbonate, or a tertiary organic base, particularly triethylamine or pyridine, or of a reaction accelerator, such as potassium iodide, is of advantage. Method E For the preparation of a quinazolinone derivative of the formula I, by reacting a benzoxazin-4-one of the formula ##STR12## wherein R.sub.1, R.sub.2 and R.sub.3 have the same meanings as in formula I, with an alkylenediamine of the formula wherein R.sub.4, R.sub.5, R.sub.6 and R.sub.7 have the same meanings as in formula I. The reaction is advantageously carried out in a solvent, such as benzene, dioxane, a lower alkanoic acid such as glacial acetic acid, or dimethylformamide, and optionally in the presence of an acid catalyst at a temperature between 50 and 150.degree. C, but preferably at the boiling point of the particular solvent which is used. The preferred solvent is glacial acetic acid. The reaction may, however, also be performed without a solvent. If the end product of methods A through E is a compound of the formula I wherein R.sub.4 is benzyl, the same may be de-benzylated to yield the corresponding compound wherein R.sub.4 is hydrogen. The de-benzylation is preferably effected by means of catalytic hydrogenation, for example with hydrogen in the presence of a catalyst such as palladized charcoal, in a solvent such as ethanol or ethylacetate, at a temperature between 25 and 75.degree. C and at a hydrogen pressure of 1 to 7 atmospheres. On the other hand, if the end product of methods A through E is a compound of the formula I wherein R.sub.4 is hydrogen; the same may be alkylated at the bridge nitrogen atom to form the corresponding compound where R.sub.4 is alkyl. The alkylation is carried out with a conventional alkylating agent, for example with an alkyl halide such as methyl iodide, ethyl iodide or isopropyl bromide, or with a dialkylsulfate such a dimethylsulfate, in a solvent such as acetone, dimethylformamide or dioxane, optionally in the presence of an inorganic or tertiary organic base, at a temperature between 0 and 50.degree. C. A methylation may also be effected by reaction with a mixture of formaldehyde and formic acid, preferably at the boiling point of said mixture. The compounds embraced by formula I are organic bases and therefore form acid addition salts with inorganic or organic acids. Examples of non-toxic, pharmacologically acceptable acid addition salts are those formed with hydrochloric acid, phosphoric acid, hydrobromic acid, sulfuric acid, lactic acid, tartaric acid, maleic acid, 8-chlorotheophylline or the like. The starting compounds of the formulas II through X are either described in the literature or may be prepared by known methods, as described in the examples below.

  该专利涉及一种新型的N-(苯基烷基氨基烷基)取代的喹唑啉酮和邻苯二氮酮及其无毒、药理学可接受的酸盐，以及制备这些化合物的各种方法。该化合物及其盐可用作降低心率和轻度降压剂。其中，化合物的通式为##STR1##其中A是##STR2##其中R.sub.1是1至3个碳原子的氢或烷基；R.sub.2是1至3个碳原子的烷氧基；R.sub.3是1至3个碳原子的烷氧基或与R.sub.2一起形成亚甲二氧基或乙二氧基；R.sub.4是氢、1至3个碳原子的烷基或苄基；R.sub.5是氢或1至3个碳原子的烷基；R.sub.6是氢或1至3个碳原子的烷氧基；R.sub.7是1至3个碳原子的烷氧基或与R.sub.6一起形成亚甲二氧基或乙二氧基；N为2或3；以及其无毒、药理学可接受的酸盐。 其中，特别优选的亚属包括通式I的化合物，其中R.sub.1和R.sub.5均为氢、甲基、乙基、正丙基或异丙基；R.sub.4是氢、甲基、乙基、正丙基、异丙基或苄基；R.sub.2、R.sub.3和R.sub.7均为甲氧基、乙氧基、正丙氧基或异丙氧基；R.sub.6是氢、甲氧基、乙氧基、正丙氧基或异丙氧基；R.sub.2和R.sub.3互相结合，形成亚甲二氧基或乙二氧基；R.sub.6和R.sub.7互相结合，形成亚甲二氧基或乙二氧基；n为2或3；以及其无毒、药理学可接受的酸盐。 其中，特别优选的亚属包括通式I的化合物，其中R.sub.2和R.sub.3分别为6-和7-位的甲氧基，或者互相结合形成亚甲二氧基或乙二氧基；R.sub.4是氢或甲基；R.sub.5是氢；R.sub.6是3-位的氢或甲氧基；R.sub.7是4-位的甲氧基或与R.sub.6一起形成亚甲二氧基或乙二氧基；n为2或3；以及其无毒、药理学可接受的酸盐。 通式I所包含的化合物可以通过以下方法制备： 方法A：通过将通式II的化合物（其中R.sub.2、R.sub.3、A和n的含义与通式I相同，Z是离去基团，例如氯、溴、碘、烷基磺酰氧或芳基磺酰氧）与通式III的苯基烷胺反应，其中R.sub.4、R.sub.5、R.sub.6和R.sub.7的含义与通式I相同。反应在惰性溶剂中进行，例如醚、四氢呋喃、甲基甲酰胺、二甲基甲酰胺、二甲基亚砜、氯苯或苯，具体温度取决于取代基Z的反应性，在-50℃至+250℃之间，但最好在所用溶剂的沸点下进行。有益的是加入酸中和剂，例如碱金属醇盐、碱金属氢氧化物、碱金属碳酸盐（尤其是碳酸钾）或三级有机碱（特别是三乙胺或吡啶），或者加入反应促进剂，例如碘化钾。 方法B：通过将通式IV的化合物（其中A、R.sub.2和R.sub.3的含义与通式I相同）与通式II的苯基烷胺反应，其中R.sub.4、R.sub.5、R.sub.6和n的含义与通式I相同，Z的含义与通式II相同。反应在惰性溶剂中进行，例如丙酮、二甲基甲酰胺、二甲基亚砜或氯苯，具体温度取决于取代基Z的反应性，在0℃至150℃之间，但最好在所用溶剂的沸点下进行。有益的是加入酸中和剂，例如碱金属醇盐、碱金属氢氧化物、碱金属碳酸盐（尤其是碳酸钾）、碱金属氨基或三级有机碱（特别是三乙胺或吡啶），或者加入反应促进剂，例如碘化钾。 方法C：通过在催化活化氢存在下，将通式V的醛（其中R.sub.2、R.sub.3、A和n的含义与通式I相同）或其缩醛与通式III的胺反应进行还原胺化反应。还原胺化反应在氢气存在下进行，使用氢化催化剂，例如钯化木炭，在5大气压下，在溶剂中进行，例如甲醇、乙醇或二噁烷，在0℃至100℃之间进行，但最好在20℃至80℃之间。 方法D：通过将通式VI的胺（其中R.sub.2、R.sub.3、R.sub.4、A和n的含义与通式I相同）与通式II的苯基化合物反应，其中R.sub.5、R.sub.6和R.sub.7的含义与通式I相同，Z的含义与通式II相同。反应在惰性溶剂中进行，例如丙酮、二氯甲烷、二甲基甲酰胺、二甲基亚砜或氯苯，具体温度取决于取代基Z的反应性，在0℃至150℃之间，但最好在所用溶剂的沸点下进行。有益的是加入酸中和剂，例如碱金属醇盐、碱金属氢氧化物、碱金属碳酸盐（尤其是碳酸钾）或三级有机碱（特别是三乙胺或吡啶），或者加入反应促进剂，例如碘化钾。 方法E：用于制备通式I的喹唑啉酮衍生物，通过将通式VII的苯并噁嗪-4-酮（其中R.sub.1、R.sub.2和R.sub.3的含义与通式I相同）与通式VIII的烷基二胺反应，其中R.sub.4、R.sub.5、R.sub.6和R.sub.7的含义与通式I相同。反应最好在溶剂中进行，例如苯、二噁烷、低级烷酸（例如冰醋酸）或二甲基甲酰胺，可选地在酸催化剂的存在下，在50℃至150℃之间进行，但最好在所用溶剂的沸点下进行。最好的溶剂是冰醋酸。但是，该反应也可以在无溶剂情况下进行。 如果方法A到E的最终产物是通式I的化合物，其中R.sub.4是苄基，则可以脱苄基以得到相应的R.sub.4为氢的化合物。最好的脱苄基方法是催化氢化，例如在乙醇或乙酸乙酯中使用氢气和钯化木炭催化剂，在25℃至75℃的温度下，在1至7大气压的氢气压力下进行。另一方面，如果方法A到E的最终产物是通式I的化合物，其中R.sub.4是氢，则可以在桥氮原子上烷基化以形成相应的R.sub.4为烷基的化合物。烷基化是使用传统的烷基化试剂进行的，例如使用烷基卤化物，例如碘化甲基、碘化乙基或溴化异丙基，或使用二烷基硫酸酯，例如二甲基硫酸酯，在丙酮、二甲基甲酰胺或二噁烷中进行，可选地在无机或三级有机碱的存在下，在0℃至50℃之间进行。也可以通过与甲醛和甲酸的混合物反应进行甲基化，最好在该混合物的沸点下进行。 通式I所包含的化合物是有机碱，因此可以与无机或有机酸形成酸加合盐。无毒、药理学可接受的酸加合盐的例子包括与盐酸、磷酸、氢溴酸、硫酸、乳酸、酒石酸、马来酸、8-氯茶碱或类似物形成的盐。通式II到X的起始化合物或已在文献中描述，或可以通过已知方法制备，具体方法如下例所示。
• Butenoic or propenoic acid derivatives
  申请人：Eisai Co., Ltd.

  公开号：EP0344577A2

  公开（公告）日：1989-12-06

  A butenoic or propenoic acid derivative having the following formula in which G is an aryl or a heterocyclic ring, R11 and R12 are hydroben or an alkyl, X is sulfur or oxygen, R2 and R3 are hydrogen, an substituent such as an alkyl and J is pyridyl or phenyl having substituents and a heterocyclic ring may be formed between R2, R3 and J is provided here and is useful in the pharmacological field.

  丁烯酸或丙烯酸衍生物具有下式，其中 G 为芳基或杂环，R11 和 R12 为氢基或烷基，X 为硫或氧，R2 和 R3 为氢，取代基如烷基，J 为吡啶基或苯基，R2、R3 和 J 之间可形成杂环，该衍生物在药理学领域非常有用。
• KUTTER, E.;EBERLEIN, W.;AUSTEL, V.;HEIDER, J.
  作者：KUTTER, E.、EBERLEIN, W.、AUSTEL, V.、HEIDER, J.

  DOI：——

  日期：——
• US3948898A
  申请人：——

  公开号：US3948898A

  公开（公告）日：1976-04-06