benzyl (2R)-2-((1E)-3-ethoxy-3-oxoprop-1-enyl)pyrrolidine-1-carboxylate | 146727-84-6

• 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: benzyl (2R)-2-((1E)-3-ethoxy-3-oxoprop-1-enyl)pyrrolidine-1-carboxylate
• 英文别名: benzyl (2R)-2-(3-ethoxy-3-oxoprop-1-enyl)pyrrolidine-1-carboxylate；ethyl (R)-3-(N-benzyloxycarbonylpyrrolidin-2-yl)-2-propenoate；1-Pyrrolidinecarboxylic acid, 2-(3-ethoxy-3-oxo-1-propenyl)-, phenylmethyl ester, [R-(E)]-；benzyl (2R)-2-[(E)-3-ethoxy-3-oxoprop-1-enyl]pyrrolidine-1-carboxylate
• CAS: 146727-84-6
• 化学式: C₁₇H₂₁NO₄
• 分子量: 303.358
• InChiKey: GLBKZCJTDIWDCT-AUECHBEKSA-N

物化性质

• 沸点：
  423.8±45.0 °C(Predicted)
• 密度：
  1.211±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  4

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  ——	(2R)-(+)-phenylmethyl 2-formylpyrrolidine-1-carboxylate	50463-82-6	C13H15NO3	233.267
  N-CBZ-吡咯烷-2-甲醛	N-benzyloxycarbonyl-2-pyrrolidinecarbaldehyde	105706-84-1	C13H15NO3	233.267
  N-Cbz-D-脯氨醇	(R)-N-benzyloxycarbonylprolinol	72597-18-3	C13H17NO3	235.283

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  ——	(R)-1-(N-benzyloxycarbonylpyrrolidin-2-yl)-3-hydroxypropene	——	C15H19NO3	261.321
  ——	3-(pyrrolidin-2-yl)prop-2-enol	146727-85-7	C15H19NO3	261.321

反应信息

• 作为反应物：
  描述：

  benzyl (2R)-2-((1E)-3-ethoxy-3-oxoprop-1-enyl)pyrrolidine-1-carboxylate 在 二异丁基氢化铝 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 生成 benzyl (2R)-2-[(E)-3-[2-bromo-4-(methylsulfamoylmethyl)-N-(2,2,2-trifluoroacetyl)anilino]prop-1-enyl]pyrrolidine-1-carboxylate
  参考文献：
  名称：

  抗偏头痛药物舒马曲坦构象受限的类似物的合成

  摘要：

  描述了抗偏头痛药物舒马曲坦的构象受限的类似物5-N-甲基氨基磺酰基甲基-3-（N-甲基吡咯烷基-2-基甲基）吲哚（1）的合成。为了在舒马普坦中合并氨基乙基侧链的新型立体异构替代物，采用了分子内Heck反应作为基石反应的3,5-二取代吲哚（1）的聚合合成方法。

  DOI：

  10.1016/s0040-4039(00)74703-4
• 作为产物：
  描述：

  D-脯氨醇 在 二甲基亚砜 、 三乙胺 、 三氟乙酸酐 作用下， 生成 benzyl (2R)-2-((1E)-3-ethoxy-3-oxoprop-1-enyl)pyrrolidine-1-carboxylate
  参考文献：
  名称：

  抗偏头痛药物舒马曲坦构象受限的类似物的合成

  摘要：

  描述了抗偏头痛药物舒马曲坦的构象受限的类似物5-N-甲基氨基磺酰基甲基-3-（N-甲基吡咯烷基-2-基甲基）吲哚（1）的合成。为了在舒马普坦中合并氨基乙基侧链的新型立体异构替代物，采用了分子内Heck反应作为基石反应的3,5-二取代吲哚（1）的聚合合成方法。

  DOI：

  10.1016/s0040-4039(00)74703-4

文献信息

• Indole derivatives
  申请人：Pfizer, Inc.

  公开号：US05747501A1

  公开（公告）日：1998-05-05

  Compounds of the formula ##STR1## where W is ##STR2## n is 0, 1, or 2; m is 0, 1, 2, or 3: Y and G are each independently oxygen or sulfur; Z is --O--, --S--, --NH, or --CH.sub.2 ; R.sub.1 is hydrogen, C.sub.1 to C.sub.8 alkyl, substituted C.sub.1 to C.sub.8 alkyl substituted with one hydroxy, C.sub.3 to C.sub.8 alkenyl, C.sub.3 to C.sub.8 alkynyl, aryl, C.sub.1 to C.sub.3 alkylaryl, C.sub.1 to C.sub.3 alkylheteroaryl, or --Q--R.sub.4 ; R.sub.2 and R.sub.3 are each independently hydrogen, C.sub.1 to C.sub.6 alkyl, aryl, C.sub.1 to C.sub.3 alkylaryl, or C.sub.1 to C.sub.3 alkylheteroaryl; R.sub.4 is cyano, trifluoromethyl, --COR.sub.9, --CO.sub.2 R.sub.9, --CONR.sub.9 R.sub.10, --OR.sub.9, --SO.sub.2 NR.sub.9 R.sub.10, or --S(O).sub.q R.sub.9 ; R.sub.9 and R.sub.10 are each independently hydrogen, C.sub.1 to C.sub.8 alkyl, C.sub.1 to C.sub.3 alkylaryl, aryl, or R.sub.9 and R.sub.10 may together be taken to form a three- to seven-membered alkyl ring or a three- to seven-membered heteroalkyl ring having 1 heteroatom of O; Q is C.sub.1 to C.sub.3 alkyl; R.sub.11 is hydrogen, --OR.sub.12, or --NHCOR.sub.12 ; R.sub.12 is hydrogen, C.sub.1 to C.sub.6 alkyl, aryl, or C.sub.1 to C.sub.3 alkylaryl; q is 0, 1, or 2; a first chiral carbon is designated by an asterisk; a second chiral carbon is designated by #; and the above aryl groups and the aryl moieties of the above alkyl-aryl groups are independently selected from phenyl and substituted phenyl, wherein said substituted phenyl may be substituted with one to three groups selected from C.sub.1 to C.sub.4 alkyl, halogen, hydroxy, cyano, carboxamido, nitro, and C.sub.1 to C.sub.4 alkoxy, and the pharmaceutically acceptable salts thereof. These compounds are useful in treating migraine and other disorders are new. These compounds are useful psychotherapeutics and are potent serotonin (5-HT.sub.1) agonists and may be used in the treatment of depression, anxiety, eating disorders, obesity, drug abuse, cluster headache, migraine, pain, and chronic paroxysmal hemicrania and headache associated with vascular disorders, and other disorders arising from deficient serotonergic neurotransmission. The compounds can also be used as centrally acting antihypertensives and vasodilators.

  化合物的公式为##STR1##其中W为##STR2##n为0、1或2；m为0、1、2或3：Y和G各自独立为氧或硫；Z为—O—、—S—、—NH或—CH.sub.2；R.sub.1为氢、C.sub.1到C.sub.8烷基、取代的C.sub.1到C.sub.8烷基，取代基为一个羟基，C.sub.3到C.sub.8烯基，C.sub.3到C.sub.8炔基，芳基，C.sub.1到C.sub.3烷基芳基，C.sub.1到C.sub.3烷基杂芳基或—Q—R.sub.4；R.sub.2和R.sub.3各自独立为氢、C.sub.1到C.sub.6烷基、芳基、C.sub.1到C.sub.3烷基芳基或C.sub.1到C.sub.3烷基杂芳基；R.sub.4为氰基、三氟甲基、—COR.sub.9、—CO.sub.2R.sub.9、—CONR.sub.9R.sub.10、—OR.sub.9、—SO.sub.2NR.sub.9R.sub.10或—S(O).sub.qR.sub.9；R.sub.9和R.sub.10各自独立为氢、C.sub.1到C.sub.8烷基、C.sub.1到C.sub.3烷基芳基、芳基，或R.sub.9和R.sub.10可一起形成一个有1个O杂原子的三到七元烷基环或三到七元杂烷基环；Q为C.sub.1到C.sub.3烷基；R.sub.11为氢、—OR.sub.12或—NHCOR.sub.12；R.sub.12为氢、C.sub.1到C.sub.6烷基、芳基或C.sub.1到C.sub.3烷基芳基；q为0、1或2；第一个手性碳由星号指定；第二个手性碳由#指定；上述芳基和上述烷基-芳基基团的芳基基团各自独立地选自苯基和取代苯基，其中所述取代苯基可用1到3个选自C.sub.1到C.sub.4烷基、卤素、羟基、氰基、羧酰胺、硝基和C.sub.1到C.sub.4烷氧基的基团取代，并且其药学上可接受的盐。这些化合物在治疗偏头痛和其他疾病方面是新的有用的。这些化合物是有用的心理治疗剂，是有效的5-羟色胺（5-HT.sub.1）激动剂，可用于治疗抑郁症、焦虑症、进食障碍、肥胖症、药物滥用、集群头痛、偏头痛、疼痛、慢性阵发性半侧头痛和与血管紊乱有关的头痛以及其他由5-羟色胺神经递质缺乏引起的疾病。这些化合物也可用作中枢作用的降压剂和扩血管剂。
• Indole derivatives as 5-HT1 agonists
  申请人：Pfizer Inc

  公开号：US05594014A1

  公开（公告）日：1997-01-14

  Compounds of the formula (I) where A represents a direct bond, C.sub.1 -C.sub.4 alkyl, or C.sub.1 -C.sub.4 alkenyl; n is 0, 1, or 2; W, X, Y, and Z are each independently oxygen, sulfur, nitrogen or carbon, provided that at least one of W, X, Y, or Z is nitrogen. These compounds are useful psychotherapeutics and are potent serotonin (5-HT.sub.1) agonists and may be used in the treatment of depression, anxiety, eating disorders, obesity, drug abuse, cluster headache, migraine, pain and chronic paroxysmal hemicrania and headache associated with vascular disorders, and other disorders arising from deficient serotonergic neurotransmission. The compounds can also be used as centrally acting antihypertensives and vasodilators.

  公式（I）的化合物，其中A代表直接键，C.sub.1-C.sub.4烷基或C.sub.1-C.sub.4烯基；n为0、1或2；W、X、Y和Z各自独立地表示氧、硫、氮或碳，但至少有一个是氮。这些化合物是有用的心理治疗药物，是有效的5-羟色胺（5-HT.sub.1）激动剂，可用于治疗抑郁症、焦虑症、进食障碍、肥胖症、药物滥用、集群性头痛、偏头痛、疼痛和慢性阵发性半头痛以及与血管障碍相关的头痛和其他因5-羟色胺能神经递质缺乏引起的疾病。这些化合物还可用作中枢作用的降压药和血管扩张剂。
• EP1746095
  申请人：——

  公开号：——

  公开（公告）日：——
• The synthesis of a conformationally restricted analog of the anti-migraine drug sumatriptan
  作者：John E. Macor、David H. Blank、Ronald J. Post、Kevin Ryan

  DOI：10.1016/s0040-4039(00)74703-4

  日期：1992.12

  The synthesis of 5-N-Methylaminosulfonylmethyl-3-(N-methylpyrrolidin-2-ylmethyl)indole (1), a conformationally restricted analog of the anti-migraine drug, sumatriptan, is described. To incorporate our novel stereogenic replacement for the aminoethyl sidechain in sumatriptan, a convergent synthesis of the 3,5-disubstituted indole (1) was employed which utilized an intramolecular Heck reaction as the

  描述了抗偏头痛药物舒马曲坦的构象受限的类似物5-N-甲基氨基磺酰基甲基-3-（N-甲基吡咯烷基-2-基甲基）吲哚（1）的合成。为了在舒马普坦中合并氨基乙基侧链的新型立体异构替代物，采用了分子内Heck反应作为基石反应的3,5-二取代吲哚（1）的聚合合成方法。