(S)-N-methyl-3-hydroxymethyl-1,2,3,4-tetrahydroisoquinoline | 54625-68-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: (S)-N-methyl-3-hydroxymethyl-1,2,3,4-tetrahydroisoquinoline
• 英文别名: (S)-(+)-<(1,2,3,4-tetrahydro-2-methyl)isoquinolin-3-yl>methanol；(3S)-1,2,3,4-tetrahydro-2-methylisoquinoline-3-methanol；2-methyl-1,2,3,4-tetrahydro-3-isoquinolinemethanol；(S)-3-hydroxymethyl-N-methyl-1,2,3,4,-tetrahydroisoquinoline；[(3S)-2-methyl-3,4-dihydro-1H-isoquinolin-3-yl]methanol
• CAS: 54625-68-2
• 化学式: C₁₁H₁₅NO
• 分子量: 177.246
• InChiKey: SWUVPLABKHJMQA-NSHDSACASA-N

物化性质

• 熔点：
  103-105 °C(Solv: dichloromethane (75-09-2); hexane (110-54-3))
• 沸点：
  289.2±20.0 °C(Predicted)
• 密度：
  1.068±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  23.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (S)-N-methyl-3-hydroxymethyl-1,2,3,4-tetrahydroisoquinoline 在 咪唑 、 ruthenium(IV) oxide 、 sodium periodate 作用下， 以 四氯化碳 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 6.5h， 生成 (+)-(3S)-3,4-dihydro-3-tert-butyldimethylsiloxymethyl-2-methyl-1(2H)-isoquinolinone
  参考文献：
  名称：

  Preparation and Diastereoselective Birch Reduction−Alkylation of Chiral 3,4-Dihydro-1(2H)-isoquinolinones. Enantiospecific Syntheses and Opioid Receptor Affinities of Several Hydro-2,3- dimethyl-1H-7,12a-methanobenzo[6,7]cycloocta[1,2-c]pyridine-9-ols

  摘要：

  Synthetic procedures have been developed to provide 2,3-disubstituted-3,4-dihydro-1(2H)-isoquinones 6, 10, and 15 from (1R,2S)-ephedrine, (1R,2R)-pseudoephedrine, and L-phenylalanine. Birch reduction of 6 and 10 gave enantiomerically related lactam enolates that were alkylated with methyl iodide, allyl bromide, benzyl bromide, p-benzyloxybenzyl bromide, and p-methoxybenzyl bromide to give 7a-7e, 11a, and 11b with diastereoselectivities > 20:1. Birch reduction-methylation of 15 gave 19 with a diastereoselectivity of >35:1. Selective reduction of the disubstituted double bond in 19 with diimide and cleavage of the tert-butyldimethylsilyl ether gave 20b, from which iodoetherification under thermodynamic control gave the iodopyran 21a; iodoetherification of 20b under kinetic control gave the iodotetrahydrofuran 22. Enantiospecific syntheses of analogues of 24 (Schultz, A. G.; Kirincich, S. J.; Rahm, R. Tetrahedron Lett. 1995, 36, 4551-4554) have been developed. Tetracycle 24 is isomeric with the potent analgesic agent levorphanol, but the bridging of the hydroisoquinoline ring by the hydroxybenzyl unit in 24 is at C(7, isoquinoline numbering) and C(8a) rather than at C(1) and C(4a) as in levorphanol. The key step in the transformation of 7d and 7e to tetracyclic phenolic amines (-)-26 and (+)-28 is the Grewe-type cyclization of 7d to 25b and 7e to 25c. K-i values for the inhibition of binding to the mu-, delta-, and kappa-opioid receptors by (-)-26, (+)-26, (+)-28, (-)-28, and (+)-32 are reported.

  DOI：

  10.1021/jo980921g
• 作为产物：
  描述：

  2-carboethoxy-1,2,3,4-tetrahydro-3-isoquinolinecarboxylic acid 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 5.0h， 以77%的产率得到(S)-N-methyl-3-hydroxymethyl-1,2,3,4-tetrahydroisoquinoline
  参考文献：
  名称：

  Preparation and Diastereoselective Birch Reduction−Alkylation of Chiral 3,4-Dihydro-1(2H)-isoquinolinones. Enantiospecific Syntheses and Opioid Receptor Affinities of Several Hydro-2,3- dimethyl-1H-7,12a-methanobenzo[6,7]cycloocta[1,2-c]pyridine-9-ols

  摘要：

  Synthetic procedures have been developed to provide 2,3-disubstituted-3,4-dihydro-1(2H)-isoquinones 6, 10, and 15 from (1R,2S)-ephedrine, (1R,2R)-pseudoephedrine, and L-phenylalanine. Birch reduction of 6 and 10 gave enantiomerically related lactam enolates that were alkylated with methyl iodide, allyl bromide, benzyl bromide, p-benzyloxybenzyl bromide, and p-methoxybenzyl bromide to give 7a-7e, 11a, and 11b with diastereoselectivities > 20:1. Birch reduction-methylation of 15 gave 19 with a diastereoselectivity of >35:1. Selective reduction of the disubstituted double bond in 19 with diimide and cleavage of the tert-butyldimethylsilyl ether gave 20b, from which iodoetherification under thermodynamic control gave the iodopyran 21a; iodoetherification of 20b under kinetic control gave the iodotetrahydrofuran 22. Enantiospecific syntheses of analogues of 24 (Schultz, A. G.; Kirincich, S. J.; Rahm, R. Tetrahedron Lett. 1995, 36, 4551-4554) have been developed. Tetracycle 24 is isomeric with the potent analgesic agent levorphanol, but the bridging of the hydroisoquinoline ring by the hydroxybenzyl unit in 24 is at C(7, isoquinoline numbering) and C(8a) rather than at C(1) and C(4a) as in levorphanol. The key step in the transformation of 7d and 7e to tetracyclic phenolic amines (-)-26 and (+)-28 is the Grewe-type cyclization of 7d to 25b and 7e to 25c. K-i values for the inhibition of binding to the mu-, delta-, and kappa-opioid receptors by (-)-26, (+)-26, (+)-28, (-)-28, and (+)-32 are reported.

  DOI：

  10.1021/jo980921g

文献信息

• NOVEL COMPOUNDS
  申请人：Gottschling Dirk

  公开号：US20110195954A1

  公开（公告）日：2011-08-11

  The present invention relates to new CGRP-antagonists of general formula I wherein U, V, X, Y, R 1 , R 2 , R 3 and R 4 are defined as mentioned in the description, the tautomers thereof, the isomers thereof, the diastereomers thereof, the enantiomers thereof, the hydrates thereof, the mixtures thereof and the salts thereof as well as the hydrates of the salts, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases, medicaments containing these compounds, the use thereof and processes for the preparation thereof.

  本发明涉及一般式I的新CGRP拮抗剂，其中U、V、X、Y、R1、R2、R3和R4如描述中所述定义，其互变异构体、异构体、顺反异构体、对映异构体、水合物、混合物及其盐，以及其盐的水合物，特别是与无机或有机酸或碱形成的生理上可接受的盐，包含这些化合物的药物、其用途以及其制备方法。
• [EN] TETRAHYDROISOQUINOLINES AS PRMT5 INHIBITORS<br/>[FR] TÉTRAHYDRO-ISOQUINOLÉINES EN TANT QU'INHIBITEURS DE PRMT5
  申请人：CTXT PTY LTD

  公开号：WO2017153513A1

  公开（公告）日：2017-09-14

  A compound of formula (I) wherein: n is 1 or 2; p is 0 or 1; R1a, R1b, R1c and R1d are independently selected from the group consisiting of H, halo, C1-4 alkoxy, C1-4 alkyl, C1-4 fluoroalkyl, C3-4 cycloalkyl, NH-C1-4 alkyl and cyano; R2a and R2b are independently selected from the group consisting of: (i) F; (ii) H; (iii) Me; and (iv) CH2OH; R2c and R2d are independently selected from the group consisting of: (i) F; (ii) H; (iii) Me; and (iv) CH2OH; R2e is H or Me; R3a and R3b are independently selected from H and Me; R4 is either H or Me; R5 is either H or Me; R6a and R6b are independently selected from H and Me; A is either (i) optionally substituted phenyl; (ii) optionally substituted naphthyl; or (iii) optionally substituted C5-12 heteroaryl; wherein when R2e is H, at least one of R1a, R1b, R1c and R1d is selected from C1-4 alkoxy, C2-4 alkyl, C1-4 fluoroalkyl, C3-4 cycloalkyl, NH-C1-4 alkyl and cyano.

  式（I）的化合物中：n为1或2；p为0或1；R1a、R1b、R1c和R1d分别独立地选自H、卤素、C1-4烷氧基、C1-4烷基、C1-4氟烷基、C3-4环烷基、NH-C1-4烷基和氰基组成的群；R2a和R2b分别独立地选自以下组成的群：（i）F；（ii）H；（iii）Me；和（iv）CH2OH；R2c和R2d分别独立地选自以下组成的群：（i）F；（ii）H；（iii）Me；和（iv）CH2OH；R2e为H或Me；R3a和R3b分别独立地选自H和Me；R4为H或Me；R5为H或Me；R6a和R6b分别独立地选自H和Me；A为（i）可选择地取代的苯基；（ii）可选择地取代的萘基；或（iii）可选择地取代的C5-12杂环芳基；其中当R2e为H时，至少有一个R1a、R1b、R1c和R1d选自C1-4烷氧基、C2-4烷基、C1-4氟烷基、C3-4环烷基、NH-C1-4烷基和氰基。
• IAP ANTAGONISTS
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：US20150238558A1

  公开（公告）日：2015-08-27

  There are disclosed compounds that modulate the activity of inhibitors of apoptosis (IAPs), pharmaceutical compositions containing said compounds and methods of treating proliferative disorders and disorders of dysregulated apoptosis, such as cancer, utilizing the compounds of the invention.

  揭示了调节凋亡抑制剂(IAPs)活性的化合物，包含这些化合物的药物组合物以及利用该发明的化合物治疗增生性疾病和失调凋亡疾病（如癌症）的方法。
• Substituted Pteridines
  申请人：Dollinger Horst

  公开号：US20070287704A1

  公开（公告）日：2007-12-13

  The invention relates to new pteridines which are suitable for treating respiratory or gastrointestinal complaints or diseases, inflammatory diseases of the joints, skin or eyes, diseases of the peripheral or central nervous system and cancers. This invention also relates to pharmaceutical compositions containing these compounds.

  该发明涉及新的蚓菌素，适用于治疗呼吸道或消化道的不适或疾病，关节、皮肤或眼睛的炎症性疾病，外周或中枢神经系统的疾病以及癌症。该发明还涉及含有这些化合物的药物组合物。
• Synthesis of Chiral Catalysts for the Enantioselective Addition of Diethylzinc to Aromatic Aldehydes
  作者：Klaus Stingl、Jürgen Martens

  DOI：10.1080/00397919208021539

  日期：1992.11

  Abstract The reaction of diethylzinc with aromatic aldehydes and (S)-porretine derived catalysts was investigated. The synthesis of new chiral catalysts is also described.

  摘要 研究了二乙基锌与芳香醛和(S)-porretine衍生催化剂的反应。还描述了新手性催化剂的合成。