2-carboethoxy-1,2,3,4-tetrahydro-3-isoquinolinecarboxylic acid | 104882-53-3

• 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: 2-carboethoxy-1,2,3,4-tetrahydro-3-isoquinolinecarboxylic acid
• 英文别名: (3S)-2-ethoxycarbonyl-3,4-dihydro-1H-isoquinoline-3-carboxylic acid
• CAS: 104882-53-3
• 化学式: C₁₃H₁₅NO₄
• 分子量: 249.266
• InChiKey: QTOSEANPJIZQGT-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.384
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  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
• 作为产物：
  描述：

  L-苯丙氨酸 、 alkaline earth salt of/the/ methylsulfuric acid 在 盐酸 、 碳酸氢钠 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 3.0h， 生成 2-carboethoxy-1,2,3,4-tetrahydro-3-isoquinolinecarboxylic acid
  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

• Peptidylaminodiols
  申请人：ABBOTT LABORATORIES

  公开号：EP0189203A2

  公开（公告）日：1986-07-30

  The invention relates to renin inhibiting compounds of the formula: wherein R10 is A is hydrogen or an N-protecting group; w is 0 or 1; B is hydrogen, hydroxy, NH, N-alkyl, loweralkyl or arylalkyl; with the proviso that when w is 1, B is NH and when w is 0, B is hydrogen, hydroxy, loweralkyl or arylalkyl; R1is loweralkyl or lipophilic or aromatic or hydrophilic amino acid side chains; m is 1-3; n is 1-3; p is 1-3; q is 1-3; s is 1-3; t is 0-2; R2 is hydrogen or loweralkyl; R3 and R4 are independently selected from loweralkyl, lipophilic or aromatic amino acid side chains; R5 and R7 are independently selected from hydrogen or loweralkyl; and R6 is hydrogen, loweralkyl, vinyl, arylalkyl or wherein R8 is hydrogen or loweralkyl, X is O, NH or S and R9 is hydrogen, loweralkyl or alkanoyl or XR9 together can be loweralkylsulfonyl, N3 or Cl.

  本发明涉及式中的肾素抑制化合物： 其中 R10 是 A是氢或N-保护基；w是0或1；B是氢、羟基、NH、N-烷基、低级烷基或芳基烷基；但当w是1时，B是NH，当w是0时，B是氢、羟基、低级烷基或芳基烷基；R1是低级烷基或亲油性或芳香性或亲水性氨基酸侧链；m是1-3；n是1-3；p是1-3；q是1-3；s是1-3；t是0-2；R2是氢或低级烷基；R3 和 R4 独立选自低烷基、亲油或芳香族氨基酸侧链；R5 和 R7 独立选自氢或低烷基；R6 是氢、低烷基、乙烯基、芳烷基或其中 R8 是氢或低烷基，X 是 O、NH 或 S，R9 是氢、低烷基或烷酰基或 XR9 合在一起可以是低烷基磺酰基、N3 或 Cl。
• US4680284A
  申请人：——

  公开号：US4680284A

  公开（公告）日：1987-07-14
• Preparation and Diastereoselective Birch Reduction−Alkylation of Chiral 3,4-Dihydro-1(2<i>H</i>)-isoquinolinones. Enantiospecific Syntheses and Opioid Receptor Affinities of Several Hydro-2,3- dimethyl-1<i>H</i>-7,12<i>a</i>-methanobenzo[6,7]cycloocta[1,2-<i>c</i>]pyridine-9-ols
  作者：Arthur G. Schultz、Timothy J. Guzi、Erika Larsson、Rainer Rahm、Kshitij Thakkar、Jean M. Bidlack

  DOI：10.1021/jo980921g

  日期：1998.10.1

  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.