1,1-dimethylethyl (3S)-3-[(tetrahydro-2H-pyran-4-yl)amino]pyrrolidine-1-carboxylate | 820985-32-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: 1,1-dimethylethyl (3S)-3-[(tetrahydro-2H-pyran-4-yl)amino]pyrrolidine-1-carboxylate
• 英文别名: tert-butyl (3S)-3-(tetrahydro-2H-pyran-4-ylamino)pyrrolidine-1-carboxylate；tert-butyl (3S)-3-(oxan-4-ylamino)pyrrolidine-1-carboxylate
• CAS: 820985-32-8
• 化学式: C₁₄H₂₆N₂O₃
• 分子量: 270.372
• InChiKey: MDEYRUABSXMTQM-LBPRGKRZSA-N

物化性质

• 沸点：
  373.9±42.0 °C(Predicted)
• 密度：
  1.09±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  50.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1,1-dimethylethyl (3S)-3-[(tetrahydro-2H-pyran-4-yl)amino]pyrrolidine-1-carboxylate 在 potassium carbonate 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 (2-methyl-benzyl)-(S)-pyrrolidin-3-yl-(tetrahydro-pyran-4-yl)-amine
  参考文献：
  名称：

  N-Benzyl-N-(tetrahydro-2H-pyran-4-yl)pyrrolidin-3-amines as selective dual serotonin/noradrenaline reuptake inhibitors

  摘要：

  A series ofN-benzy]-P[-(tetrahydro-2H-pyran-4-yl)pyrrolidin-3-amine monoamine reuptake inhibitors are described. Selective dual 5-HT and NA reuptake inhibition was achieved, and analogues with weak CYP2136 inhibition, good human in vitro metabolic stability and wide ligand selectivity, such as 12b, were identified. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.01.020
• 作为产物：
  描述：

  四氢吡喃酮 、 (3S)-3-(异丙基氨基)吡咯烷-1-甲酸叔丁酯 在 三乙酰氧基硼氢化钠 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 120.33h， 生成 1,1-dimethylethyl (3S)-3-[(tetrahydro-2H-pyran-4-yl)amino]pyrrolidine-1-carboxylate
  参考文献：
  名称：

  [EN] 3-AMINOPYRROLIDINES AS INHIBITORS OF MONOAMINE UPTAKE
  [FR] 3-AMINOPYRROLIDINES UTILISEES COMME INHIBITEURS DE L'APPORT DE MONOAMINE

  摘要：

  本发明提供了式（I）的化合物及其药学上可接受的盐，用于抑制一个或多个生理活性单胺（5-羟色胺、去甲肾上腺素和多巴胺）的摄取。

  公开号：

  WO2005000811A1

文献信息

• Novel compounds
  申请人：Fish Vincent Paul

  公开号：US20060111429A1

  公开（公告）日：2006-05-25

  A compound of Formula (I) and pharmaceutically and/or veterinarily acceptable derivatives thereof, wherein: R 1 , R 2 , R 3 and R 20 are each independently H, Cl, Br, F, I, CF 3 , OCF 3 , Me or Et; R 4 is het or C 3-7 cycloalkyl optionally substituted by C 1-4 alkyl, C 1-4 alkoxy, alkoxyalkyl containing 2 to 4 carbon atoms or —S—(C 1-4 alkyl); a is 0 or 1; and het is a non-aromatic 4-, 5- or 6-membered heterocycle which contains at least one N, O or S heteroatom, optionally fused to a 5- or 6-membered carbocyclic group or a second 4-, 5- or 6-membered heterocycle which contains at least one N, O or S heteroatom, wherein the het group is optionally substituted by at least one substituent independently selected from C 1-8 alkyl, C 1-8 alkoxy, OH, halo, CF 3 , OCF 3 , SCF 3 , hydroxy-C 1-6 alkyl, C 1-4 alkoxy-C 1-6 alkyl and C 1-4 alkyl-S—C 1-4 alkyl; provided that at least one of R 1 , R 2 and R 3 are other than H. The compounds of the invention exhibit activity as both serotonin and noradrenaline re-uptake inhibitors and therefore have utility in a variety of therapeutic areas, for example urinary incontinence.

  公式（I）的化合物及其药学和/或兽医学上可接受的衍生物，其中：R1、R2、R3和R20分别独立地为H、Cl、Br、F、I、CF3、OCF3、Me或Et；R4为杂原子或C3-7环烷基，可选择地被C1-4烷基、C1-4烷氧基、含有2至4个碳原子的烷氧基烷基或—S—（C1-4烷基）取代；a为0或1；het为非芳香性4、5或6成员杂环，其中至少含有一个N、O或S杂原子，可选择地与含有至少一个N、O或S杂原子的5或6成员碳环基或第二个含有至少一个N、O或S杂原子的4、5或6成员杂环融合，其中het基可选择地被至少一个从C1-8烷基、C1-8烷氧基、OH、卤素、CF3、OCF3、SCF3、羟基-C1-6烷基、C1-4烷氧基-C1-6烷基和C1-4烷基-S—C1-4烷基中独立选择的取代基取代；但至少其中一个R1、R2和R3不为H。本发明的化合物表现出活性，既作为5-羟色胺又作为去甲肾上腺素的再摄取抑制剂，因此在多种治疗领域具有用途，例如尿失禁。
• N-Pyrrolidin-3YL-Amide Derivatives As Serotonin and Noradrenalin Re-Uptake Inhibitors
  申请人：Fish Paul Vincent

  公开号：US20090239928A1

  公开（公告）日：2009-09-24

  A compound of Formula (I) and pharmaceutically and/or veterinarily acceptable derivatives thereof, wherein: R 1 is H, C 1-6 alkyl, —C(A)D, C 3-8 cycloalkyl, aryl, het, aryl-C 1-4 alkyl or het-C 1-4 alkyl, wherein the cycloalkyl, aryl or het groups are optionally substituted by at least one substituent independently selected from C 1-8 allkyl, C 1-8 alkoxy, OH, halo, CF 3 , OCHF 2 , OCF3, SCF 3 , hydroxy-C 1-6 alkyl, C 1-4 alkoxy-C 1-6 alkyl and C 1-4 alkyl-S—C 1-4 alkyl; A is S or O; D is H, C 1-6 alkyl, aryl, het, aryl-C 1-4 alkyl or het-C 1-4 alkyl; R 2 represents aryl 1 or het 1 , each of which is substituted by at least one substituent independently selected from B, provided that when R 2 is substituted by halo then it is also substituted with at least one other substituent independently selected from B other than halo; B represents aryl 2 , het 2 , Oaryl 2 , Ohet 2 , Sarl 2 , Shet 2 , SC 1-6 alkyl, halogen, CHF 2 , OCHF 2 , CF 2 CF 3 , CH 2 CF 3 , CF2CH 3 , aryl 2 -C 1-4 alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl-C 1-4 alkyl, C 3-6 cycloalkylC 1-4 alkoxy, C 3-6 cycloalkyl-O—C 1-4 alkyl, C 3-6 cycloalkyl-C 1-4 alkoxy-C 1-4 alkyl, OC 3-6 cycloalkyl, SC 3-6 cycloalkyl; wherein the aryl 2 and het 2 groups are optionally substituted by at least one group selected from C 1-6 alkyl, C 3-6 cycloalkyl, C 1-6 alkoxy, OC 3-6 cycloalkyl, halo, CN, OH, CF 3 , CHF 2 , OCF 3 , OCHF 2 , hydroxyC 1 $alkyl, C 1-4 alkoxy-C 1-4 alkyl, SC 1-6 alkyl and SCF 3 ; n is 1 or 2, provided that when n is 1, m is 0 or 1 and when n is 2, m is 0, wherein if m is 0, then * represents a chiral centre; R 3 is H, C 1-6 alkyl, C 3-8 cycloalkyl, C 3-8 cycloalkylC 1-6 alkyl, aryl 3 , het 3 , aryl 3 -C 1-4 alkyl or het 3 -C 1-4 alkyl, wherein the C 3-8 cycloalkyl, aryl 3 or het 3 groups are optionally substituted by at least one substituent independently selected from C 1-6 alkyl, C 1-6 alkoxy, CN, OH, halo, CF 3 , OCF 3 , SCF 3 , hydroxy-C 1-6 alkyl, C 1-4 alkoxy-C 1-6 alkyl and C 1-4 alkyl-S—C 1-4 alkyl; at each occurrence aryl, aryl 1 , aryl 2 and aryl 3 independently represent phenyl, naphthyl, anthracyl or phenanthryl; het 1 represents an aromatic 5- or 6-membered heterocycle which contains at least one N, O or S heteroatom, optionally fused to an aryl group; at each occurrence het, het 2 , and het 3 independently represents an aromatic or non-aromatic 4-, 5- or 6-membered heterocycle which contains at least one N, O or S heteroatom, optionally fused to a 5- or 6-membered carbocyclic group or a second 4-, 5- or 6membered heterocycle which contains at least one N, O or S heteroatom.

  公式（I）的化合物及其药学和/或兽医学上可接受的衍生物，其中：R1为H，C1-6烷基，-C（A）D，C3-8环烷基，芳基，杂环基，芳基-C1-4烷基或杂环基-C1-4烷基，其中环烷基，芳基或杂环基可以选择地被至少一个取代基取代，该取代基独立地选择自C1-8烷基，C1-8烷氧基，OH，卤素，CF3，OCHF2，OCF3，SCF3，羟基-C1-6烷基，C1-4烷氧基-C1-6烷基和C1-4烷基-S-C1-4烷基；A为S或O；D为H，C1-6烷基，芳基，杂环基，芳基-C1-4烷基或杂环基-C1-4烷基；R2代表芳基1或杂环基1，每个都被至少一个取代基独立地选择自B，但当R2被卤素取代时，它还被至少一个取代基独立地选择自B，该取代基不是卤素；B代表芳基2，杂环基2，O芳基2，Ohet2，S芳基2，Shet2，SC1-6烷基，卤素，CHF2，OCHF2，CF2CF3，CH2CF3，CF2CH3，芳基2-C1-4烷基，C3-6环烷基，C3-6环烷基-C1-4烷基，C3-6环烷基C1-4烷氧基，C3-6环烷基-O-C1-4烷基，C3-6环烷基-C1-4烷氧基-C1-4烷基，OC3-6环烷基，SC3-6环烷基；其中芳基2和杂环基2可以选择地被至少一个基团取代，所述基团选择自C1-6烷基，C3-6环烷基，C1-6烷氧基，OC3-6环烷基，卤素，CN，OH，CF3，CHF2，OCF3，OCHF2，羟基C1$烷基，C1-4烷氧基-C1-4烷基，SC1-6烷基和SCF3；n为1或2，但当n为1时，m为0或1，当n为2时，m为0，其中如果m为0，则*表示手性中心；R3为H，C1-6烷基，C3-8环烷基，C3-8环烷基C1-6烷基，芳基3，杂环基3，芳基3-C1-4烷基或杂环基3-C1-4烷基，其中C3-8环烷基，芳基3或杂环基3可以选择地被至少一个取代基取代，该取代基独立地选择自C1-6烷基，C1-6烷氧基，CN，OH，卤素，CF3，OCF3，SCF3，羟基-C1-6烷基，C1-4烷氧基-C1-6烷基和C1-4烷基-S-C1-4烷基；在每次出现中，芳基，芳基1，芳基2和芳基3独立地表示苯基，萘基，蒽基或菲基；het1表示至少含有一个N，O或S杂原子的芳香5-或6元杂环，可选择地与芳基团融合；在每次出现中，het，het2和het3独立地表示至少含有一个N，O或S杂原子的芳香或非芳香4、5或6元杂环，可选择地与5-或6元杂环碳环基或含有至少一个N，O或S杂原子的第二个4、5或6元杂环融合。
• 3-Aminopyrrolidines as inhibitors of monoamine uptake
  申请人：Beadle David Christopher

  公开号：US20060270713A1

  公开（公告）日：2006-11-30

  The present invention provides compounds of formula (I) and pharmaceutically acceptable salts thereof, which are useful for the inhibition of the uptake of one or more physiologically active monoamines (serotonin, norepinephrine, and dopamine).

  本发明提供了式（I）化合物及其药学上可接受的盐，用于抑制一个或多个生理活性单胺（血清素、去甲肾上腺素和多巴胺）的摄取。
• Amides useful as monoamine re-uptake inhibitors
  申请人：Pfizer Inc.

  公开号：US07122683B2

  公开（公告）日：2006-10-17

  A compound of Formula (I) and pharmaceutically and/or veterinarily acceptable derivatives thereof, wherein: R1, R2, R3 and R20 are each independently H, Cl, Br, F, I, CF3, OCF3, Me or Et; R4 is het or C3-7 cycloalkyl optionally substituted by C1-4 alkyl, C1-4 alkoxy, alkoxyalkyl containing 2 to 4 carbon atoms or —S—(C1-4 alkyl); a is 0 or 1; and het is a non-aromatic 4-, 5- or 6-membered heterocycle which contains at least one N, O or S heteroatom, optionally fused to a 5- or 6-membered carbocyclic group or a second 4-, 5- or 6-membered heterocycle which contains at least one N, O or S heteroatom, wherein the het group is optionally substituted by at least one substituent independently selected from C1-8alkyl, C1-8alkoxy, OH, halo, CF3, OCF3, SCF3, hydroxy-C1-6alkyl, C1-4alkoxy-C1-6alkyl and C1-4alkyl-S—C1-4alkyl; provided that at least one of R1, R2 and R3 are other than H. The compounds of the invention exhibit activity as both serotonin and noradrenaline re-uptake inhibitors and therefore have utility in a variety of therapeutic areas, for example urinary incontinence.

  公式（I）及其药学和/或兽医学上可接受的衍生物的化合物，其中：R1、R2、R3和R20分别独立地为H、Cl、Br、F、I、CF3、OCF3、Me或Et；R4为het或C3-7环烷，可选地被C1-4烷基、C1-4烷氧基、含2至4个碳原子的烷氧基烷基或-S-（C1-4烷基）取代；a为0或1；而het是一种非芳香性4、5或6元杂环，其中至少含有一个N、O或S杂原子，可选地融合到一个5或6元的碳环基团或第二个含有至少一个N、O或S杂原子的4、5或6元杂环中，其中het基团可选地被至少一种取代基独立地选择自C1-8烷基、C1-8烷氧基、OH、卤素、CF3、OCF3、SCF3、羟基-C1-6烷基、C1-4烷氧基-C1-6烷基和C1-4烷基-S-C1-4烷基；但至少有一个R1、R2或R3不为H。该发明的化合物表现出作为5-羟色胺和去甲肾上腺素再摄取抑制剂的活性，因此在多种治疗领域，例如尿失禁中具有实用性。
• [EN] TREATMENT OF PERVASIVE DEVELOPMENTAL DISORDERS WITH NOREPINEPHRINE REUPTAKE INHIBITORS<br/>[FR] TRAITEMENT DES TROUBLES PROFONDS DU DEVELOPPEMENT AU MOYEN D'INHIBITEURS DE LA RECAPTURE DE LA NOREPINEPHRINE
  申请人：LILLY CO ELI

  公开号：WO2005020976A3

  公开（公告）日：2005-06-16