2-(2-methylphenyl)-3-methylbutyronitrile | 105902-47-4

• 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: 2-(2-methylphenyl)-3-methylbutyronitrile
• 英文别名: α-isopropyl-2-methylbenzyl cyanide；3-methyl-2-o-tolyl-butyronitrile；3-Methyl-2-o-tolyl-butyronitril；3-Methyl-2-(2-methylphenyl)butanenitrile
• CAS: 105902-47-4
• 化学式: C₁₂H₁₅N
• mdl: MFCD16301515
• 分子量: 173.258
• InChiKey: GTFUVNONPTVSIK-UHFFFAOYSA-N

物化性质

• 沸点：
  91-98 °C(Press: 1.8 Torr)
• 密度：
  0.949±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.416
• 拓扑面积：
  23.8
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  2-(2-methylphenyl)-3-methylbutyronitrile 在 sodium tetrahydroborate 、 草酸 、 sodium amide 作用下， 以 甲醇 为溶剂， 反应 3.5h， 生成 5-[3-(3-methoxyphenoxy)propylamino]-2-(2-methylphenyl)-2-propan-2-ylpentanenitrile
  参考文献：
  名称：

  Novel phenoxyalkylamine derivatives. IV. Synthesis, Ca2+-antagonistic activity and quantitative structure-activity analysis of .ALPHA.-isopropyl-.ALPHA.-(3-(3-(3-methoxyphenoxy)propylamino)propyl)-.ALPHA.-phenylacetonitrile derivatives.

  摘要：

  制备了α-异丙基-α-[3-[3-(3-甲氧基苯氧基)丙氨基]丙基]-α-苯乙腈衍生物，并评估了它们的 Ca2+ 拮抗活性。在这些化合物中，发现在 A 环上具有 m-OMe、p-F、p-Cl、3，4-(OMe) 2 和 3，5-(OMe) 2 取代基的 N-Me 衍生物比维拉帕米具有更高的 Ca2+ 拮抗活性。利用物理化学取代基参数和回归分析对 A 环上取代基的影响进行了定量研究。分析结果表明，π值接近于零的取代基对活性有利，而 m 和 p 取代基存在最佳立体条件，相当于 m-OMe 和 p-F 或 p-Cl。对同时改变 A 环、苯氧基苯环（B 环）和季碳原子上的取代基的全系列类似物进行的分析表明，除了特定位置的立体效应和疏水效应外，还存在最佳的分子疏水性，这可能参与了向作用部位的迁移过程。

  DOI：

  10.1248/cpb.36.4103
• 作为产物：
  描述：

  邻甲基苯乙腈 在 sodium amide 、 甲苯 、 2-溴丙烷 作用下， 生成 2-(2-methylphenyl)-3-methylbutyronitrile
  参考文献：
  名称：

  Azulenes. IX.¹ Migration of the Isopropyl Group during the Synthesis of 1-Isopropyl-8-methylazulene

  摘要：

  DOI：

  10.1021/ja01545a055

文献信息

• Some New Analogues of Verapamil and Mepamil. Synthesis and Basic Pharmacological Properties
  作者：Gabriel Butora、Ludvík Bláha、Miroslav Rajšner、Ivan Helfert

  DOI：10.1135/cccc19921967

  日期：——

  Some new analogues of verapamil (Ia) and mepamil (Ib), calcium antagonists of arylalkylamine type, were synthesized and screened for cardiovascular activities. The basic structure was modified a) on the phenyl ring, attached to the quaternary carbon, b) on the alkyl group, attached to the quaternary carbon and c) on the alkylamino group, attached in position 3 to the n-propyl fragment. Except of 2-(2-chlorophenyl)-2-isopropyl-5-(N-methylhomoveratrylamino)valeronitrile (VIa), all the synthesized compounds exhibited lower hypotensive activity, than the mother compound, verapamil.

  一些新的维拉帕米（Ia）和美帕米（Ib）的类似物，属于芳基烷胺型钙拮抗剂，已经合成并进行心血管活性筛选。基本结构进行了修改：a）在苯环上，连接到季铵碳上，b）在烷基团上，连接到季铵碳上，c）在烷基氨基团上，连接到n-丙基片段的位置3。除了2-(2-氯苯基)-2-异丙基-5-(N-甲基同位素香豆酰胺)戊腈（VIa）外，所有合成的化合物表现出较低的降压活性，低于母化合物维拉帕米。
• N-arylalkylderivatives of 2-aminomethyl-2,3-dihydro-1,4-benzodioxine and
  申请人：Vyzkumny Ustav Pro Farmacii A Biochemii s.p.

  公开号：US05424456A1

  公开（公告）日：1995-06-13

  New N-Arylalkylderivatives of 2-aminomethyl-2,3-dihydro-1,4-benzodioxine and its (+)- and (-)- enantiomers represented by general formula (I), where R.sub.1, R.sub.2 and R.sub.3 represent H, or R.sub.1 and R.sub.2 represent H and R.sub.3 represent H or R.sub.1 and R.sub.2 represent methoxy and R.sub.3 represents H and their pharmaceutically acceptable organic or inorganic acid addition salts exhibit in pharmacological tests pronounced hypotensive activity as a result of their calcium channel blocking and alpha.sub.1 -adrenergic blocking activity and pronounced antithrombotic action. In a form of pharmaceutical preparations, they are suitable for the treatment and prevention of cardiovascular diseases and other disorders. New compounds of general formula (I) by N-alkylation of 2-aminomethyl-2,3-dihydro-1,4-benzodioxine and its (+)- and (-)-enantiomers by derivatives of 2 phenyl-2-isopropyl-5-oxovaleronitrile under the conditions of reductive alkylation or with derivatives of 5-bromo-2-phenyl-2-isopropylvaleronitrile, which can be prepared by allylation of alpha-isopropylbenzyl cyanide and subsequent addition of hydrogen bromide under free radical conditions to the obtained alpha-allyl-alpha-isopropylbenzyl cyanide and its derivatives.

  2-氨甲基-2,3-二氢-1,4-苯并二氧杂环的新的N-芳基烷基衍生物及其(+)-和(-)-对映异构体由通式(I)表示，其中R.sub.1，R.sub.2和R.sub.3代表H，或者R.sub.1和R.sub.2代表H且R.sub.3代表H，或者R.sub.1和R.sub.2代表甲氧基且R.sub.3代表H，以及它们的药物可接受的有机或无机酸盐，在药理学测试中表现出显著的降压活性，这是由于它们的钙通道阻滞和α.sub.1-肾上腺素能阻滞活性以及显著的抗血栓作用。以药物制剂的形式，它们适用于心血管疾病和其他疾病的治疗和预防。通过2-苯基-2-异丙基-5-氧代戊二腈衍生物的还原烷基化条件或5-溴-2-苯基-2-异丙基戊二腈衍生物的衍生物对2-氨甲基-2,3-二氢-1,4-苯并二氧杂环及其(+)-和(-)-对映异构体进行N-烷基化，这些衍生物可以通过α-异丙基苄基氰化物的联苄反应和对所得的α-烯丙基-α-异丙基苄基氰化物及其衍生物进行自由基条件下的氢溴酸加成来制备。
• 2-Isopropyl-2-(2-methylphenyl)-5-(N-methyl-N-homoveratr
  申请人：Spofa, spojene podniky pro zdravotnickou

  公开号：US04847403A1

  公开（公告）日：1989-07-11

  2-Isopropyl-2-(2-methylphenyl)-5-(N-methylhomoveratrylamino)-valeronitrile ("mepamil") of the Formula I: ##STR1## preferably administered in the form of water-soluble acid addition salts such as e.g. hydrochloride. The claimed compound is advantageously prepared by alkylation of 2-(2-methylphenyl)-3-methylbutyronitrile with 3,3-diethoxypropylchloride. Subsequently, the obtained 5,5-diethoxy-2-isopropyl-2-(2-Methylphenyl)-valeronitrile is mildly, acidically hydrolisized to yield the appropriate aldehye, i.e. 2-isopropyl-2-(2-methylphenyl)-5-oxovaleronitrile. This aldehyde is then reacted with N-methylhomoveratrylamine under conditions of reductive alkylation, suitably by catalytic hydrogenation over a platinum or palladium catalyst or by chemical reduction with the use of formic acid as a reducing agent. The resulting base is optionally converted by neutralization with a pharmaceutically acceptable organic or inorganic acid, i.e. hydrochloric or fumaric acid, into the corresponding acid addition salt.

  化合物2-异丙基-2-(2-甲基苯基)-5-(N-甲基同香豆醇基)-戊腈（“mepamil”）的化学式为I：##STR1## 最好以水溶性酸盐的形式（例如盐酸盐）进行给药。所述化合物优选通过将2-(2-甲基苯基)-3-甲基丁腈与3,3-二乙氧基丙基氯化物烷基化制备而得。随后，所得的5,5-二乙氧基-2-异丙基-2-(2-甲基苯基)-戊腈被轻微的酸性水解以得到适当的醛，即2-异丙基-2-(2-甲基苯基)-5-氧代戊腈。然后，在还原烷基化的条件下，将该醛与N-甲基同香豆醇胺反应，适宜地通过铂或钯催化氢化或使用甲酸作为还原剂的化学还原反应。所得到的碱可以通过与药学上可接受的有机或无机酸（如盐酸或富马酸）中和而选择性地转化为相应的酸盐。
• 2-Isopropyl-2-phenyl-5-(N-methyl-2-phenylethylamino)-valeronitrile derivatives and processes for their preparation
  申请人：SPOFA Spojené Podniky Pro Zdravotnickou Vyrobu

  公开号：EP0257768A1

  公开（公告）日：1988-03-02

  2-Isopropyl-2-phenyl-5-1N-methyl-2-phenylethylaminol- valeronitrile derivatives of the general formula I wherein R is a methyl, chlorine, bromine, C1 to C4 alkoxyl or methylthio group, preferably administered in the form of soluble acid addition salts, notablythe 2-methylphenyl analog as its hydrochloride, possess significant calcium-antagonistic and cardiac antiarrythmic activity. Preparation is by alkylation of the corresponding butyroni- triie derivative (obtained from the respective substituted benzyicyanide by alkylation with isopropylbromide) by 3,3-diethoxypropylchloride, subsequent acidic hydrolysis of the 5,5-diethoxy-2-isopropyl-2-phenylvaleronitrile derivative obtained to the appropriate aldehyde, and reductive alkylation of this aldehyde with N-methylhomoveratrylamine by catalytic hydrogenation over a platinum or palladium catalyst or chemical reduction using formic acid. The resulting base is optionally neutralized with a pharmaceutically acceptable organic or inorganic acid, e.g. hydrochloric or fumaric acid, into the corresponding acid addition salt.

  通式 I 的 2-异丙基-2-苯基-5-1N-甲基-2-苯乙基氨基戊腈衍生物，其中 R 是甲基、氯、溴、C1 至 C4 烷氧基或甲硫基。 其中 R 是甲基、氯、溴、C1 至 C4 烷氧基或甲硫基，最好以可溶性酸加成盐的形式给药，特别是 2-甲基苯基类似物盐酸盐，具有显著的钙拮抗剂和抗心律失常活性。 制备方法是用 3,3-二乙氧基丙基盐酸盐烷基化相应的丁腈三酸衍生物（从各自取代的苄基氰化物中用异丙基溴烷基化得到），然后酸性水解 5、5-二乙氧基-2-异丙基-2-苯基戊腈衍生物的酸性水解，得到相应的醛，然后通过铂或钯催化剂上的催化氢化作用或甲酸的化学还原作用，将该醛与 N-甲基高藜芦胺还原烷基化。得到的碱可选择与药学上可接受的有机酸或无机酸（如盐酸或富马酸）中和，生成相应的酸加成盐。
• MITANI, KAZUYA;SAKURAI, SHUNICHIRO;SUZUKI, TOSHIHIRO;NORIKAWA, KOJI;KOSHI+, CHEM. AND PHARM. BULL., 36,(1988) N0, C. 4101-4120
  作者：MITANI, KAZUYA、SAKURAI, SHUNICHIRO、SUZUKI, TOSHIHIRO、NORIKAWA, KOJI、KOSHI+

  DOI：——

  日期：——