tert-butyl(3S,4S)-3-hydroxy-4-(hydroxymethyl)piperidine-1-carboxylate | 1260593-54-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: tert-butyl(3S,4S)-3-hydroxy-4-(hydroxymethyl)piperidine-1-carboxylate
• 英文别名: (3S,4S)-tert-Butyl 3-hydroxy-4-(hydroxymethyl)piperidine-1-carboxylate；tert-butyl (3S,4S)-3-hydroxy-4-(hydroxymethyl)piperidine-1-carboxylate
• CAS: 1260593-54-1
• 化学式: C₁₁H₂₁NO₄
• 分子量: 231.292
• InChiKey: ULXATPSIGBJTPI-DTWKUNHWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  70
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl(3S,4S)-3-hydroxy-4-(hydroxymethyl)piperidine-1-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 生成 (+/-)-trans-4-(Hydroxymethyl)piperidin-3-ol
  参考文献：
  名称：

  (+)-金鸡胺酮及其简化衍生物的设计、合成和单胺氧化酶抑制活性

  摘要：

  通过(+)-金鸡胺酮及其对映体的全合成确定了吲哚生物碱(+)-金鸡胺酮的绝对结构。该研究的主要重点是手性顺式-3,4-二取代哌啶的两种对映异构体的对映选择性合成。我们还评估了这些对映体的单胺氧化酶 (MAO) 抑制活性。此外，合成了其结构简化的衍生物，没有任何手性中心。其中两种衍生物显示出比(+)-金鸡胺酮更强的MAO抑制活性。

  DOI：

  10.1021/acsmedchemlett.1c00310
• 作为产物：
  描述：

  1-哌啶羧酸,4-(甲氧基亚甲基)-,1,1-二甲基乙基酯 在 sodium tetrahydroborate 、 cerium(III) chloride heptahydrate 、 palladium diacetate 、 溶剂黄146 、 (+)-二异松蒎烯基硼烷 、 对苯醌 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 76.5h， 生成 tert-butyl(3S,4S)-3-hydroxy-4-(hydroxymethyl)piperidine-1-carboxylate
  参考文献：
  名称：

  (+)-金鸡胺酮及其简化衍生物的设计、合成和单胺氧化酶抑制活性

  摘要：

  通过(+)-金鸡胺酮及其对映体的全合成确定了吲哚生物碱(+)-金鸡胺酮的绝对结构。该研究的主要重点是手性顺式-3,4-二取代哌啶的两种对映异构体的对映选择性合成。我们还评估了这些对映体的单胺氧化酶 (MAO) 抑制活性。此外，合成了其结构简化的衍生物，没有任何手性中心。其中两种衍生物显示出比(+)-金鸡胺酮更强的MAO抑制活性。

  DOI：

  10.1021/acsmedchemlett.1c00310
• 作为试剂：
  描述：

  (+/-)-trans-4-(Hydroxymethyl)piperidin-3-ol 、 二碳酸二叔丁酯 在 甲醇 、 tert-butyl(3S,4S)-3-hydroxy-4-(hydroxymethyl)piperidine-1-carboxylate 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以yielding 13.7 g (68.8%) of 1,1-dimethylethyl(trans)-3-hydroxy-4-(hydroxymethyl)-1-piperidinecarboxylate (intermediate 1-b)的产率得到tert-butyl(3S,4S)-3-hydroxy-4-(hydroxymethyl)piperidine-1-carboxylate
  参考文献：
  名称：

  Gastrokinetic monocyclic benzamides of 3- or 4-substituted 4-(aminomethyl)-piperidine derivatives

  摘要：

  本发明涉及式（I）化合物，其立体化学异构体形式，其N-氧化物形式或其药学上可接受的酸加成盐，其中R1是C1-6烷氧基，C2-6烯氧基或C2-6炔基氧基；R2是氢，C1-6烷基或C1-6烷氧基；R3是氢或卤素；R4是氢或C1-6烷基；R5是氢或C1-6烷基；L是C3-6环烷基，C5-6环烷酮，C2-6烯基，或L是式—Alk—R6—，Alk—X—R7，-Alk-Y—C（═O）—R9或-Alk-Y—C（═O）—NR11R12的基团，其中每个Alk是C1-12烷二基；R6是氢，氰基，C1-6烷基磺酰胺基，C3-6环烷基，C5-6环烷酮或杂环环系；R7是氢，C1-6烷基，羟基C1-6烷基，C3-6环烷基或杂环环系；X是O，S，SO2或NR8；其中R8是氢或C1-6烷基；R9是氢，C1-6烷基，C3-6环烷基，C1-6烷氧基或羟基；Y是NR10或直接键；其中R10是氢或C1-6烷基；R11和R12各自独立地是氢，C1-6烷基，C3-6环烷基，或R11和R12与氮原子结合可形成可选择取代的吡咯烷基，哌啶基，哌嗪基或4-吗啉基环。公开了制备所述产品的方法，包含所述产品的制剂以及它们作为药物的用途，特别是用于治疗与胃排空障碍有关的疾病。

  公开号：

  US06452013B1

文献信息

• [EN] COMPOUNDS ACTIVE TOWARDS NUCLEAR RECEPTORS<br/>[FR] COMPOSÉS ACTIFS VIS-À-VIS DES RÉCEPTEURS NUCLÉAIRES
  申请人：NUEVOLUTION AS

  公开号：WO2021124279A1

  公开（公告）日：2021-06-24

  Disclosed are compounds active towards nuclear receptors, pharmaceutical compositions containing the compounds and use of the compounds in therapy.

  揭示了对核受体活性的化合物，包含这些化合物的药物组合物以及这些化合物在治疗中的用途。
• 4-(aminomethyl)-piperidine benzamides for treating gastrointestinal disorders
  申请人：——

  公开号：US20030181456A1

  公开（公告）日：2003-09-25

  The present invention of compounds of formula (I) 1 a stereochemically isomeric form thereof, an N-oxide form thereof or a pharmaceutically acceptable acid addition salt thereof, —R 1 —R 2 — is a bivalent radical of formula wherein in said bivalent radicals one or two hydrogen atoms may be substituted with C 1-6 alkyl or hydroxy; R 3 is hydrogen or halo; R 4 is hydrogen or C 1-6 alkyl; R 5 is hydrogen or C 1-6 alkyl; L is C 3-6 cycloalkyl, oxoC 5-6 cycloalkyl, C 2-6 alkenyl, or L is a radical of formula -Alk-R 6 —, Alk-X—R 7 , -Alk-Y—C(═O)—R 9 , or -Alk-Y—C(═O)—NR 11 R 12 wherein each Alk is C 1-12 alkanediyl; and R 6 is hydrogen, amino, cyano, C 1-6 alkylsulfonylamino, C 3-6 cycloalkyl, oxoC 5-6 cycloalkyl, aryl or a heterocyclic ringsystem; R 7 is hydrogen, C 1-6 alkyl, hydroxyC 1-6 alkyl, C 3-6 cycloalkyl, aryl or a heterocyclic ringsystem; X is O, S, SO 2 or NR 8 ; said R 8 being hydrogen or C 1-6 alkyl; R 9 is hydrogen, C 1-6 alkyl, C 3-6 cycloalkyl, C 1-6 alkyloxy, hydroxy or aryl; Y is a direct bond or NR 10 ; said R 10 being hydrogen, or C 1-6 alkyl; R 11 and R 12 each independently are hydrogen, C 1-6 alkyl, C 3-6 cycloalkyl, or R 11 and R 12 combined with the nitrogen atom may form an optionally substituted pyrrolidinyl, piperidinyl, piperazinyl or 4 -morpholinyl ring. Processes for preparing said products, formulations comprising said products and their use as a medicine are disclosed, in particular for treating or preventing gastrointestinal disorders.

  本发明涉及一种化合物，其化学式为（I）1a立体化学异构体形式，其N-氧化物形式或药学上可接受的酸盐形式，其中-R1-R2-是一个化学式的二价基团，在所述的二价基团中，一个或两个氢原子可以被C1-6烷基或羟基取代；R3是氢或卤素；R4是氢或C1-6烷基；R5是氢或C1-6烷基；L是C3-6环烷基，氧代C5-6环烷基，C2-6烯基，或L是化学式-Alk-R6-，Alk-X-R7，-Alk-Y-C(═O)-R9，或-Alk-Y-C(═O)-NR11R12的基团，其中每个Alk是C1-12烷基二亚基；R6是氢，氨基，氰基，C1-6烷基磺酰氨基，C3-6环烷基，氧代C5-6环烷基，芳基或杂环环系统；R7是氢，C1-6烷基，羟基C1-6烷基，C3-6环烷基，芳基或杂环环系统；X是O，S，SO2或NR8；其中R8是氢或C1-6烷基；R9是氢，C1-6烷基，C3-6环烷基，C1-6烷氧基，羟基或芳基；Y是直接键或NR10；其中R10是氢或C1-6烷基；R11和R12各自独立地是氢，C1-6烷基，C3-6环烷基，或R11和R12与氮原子结合可以形成一个可选取代的吡咯烷基，哌啶基，哌嗪基或4-吗啉基环。本发明还公开了制备所述产品的方法，包含所述产品的制剂以及其作为药物的用途，特别是用于治疗或预防胃肠道疾病。
• Bicyclic benzamides of 3- or 4-substituted 4-(aminomethyl)-piperidine derivatives
  申请人：Bosmans Rene Marie Andre Jean-Paul

  公开号：US20060142341A1

  公开（公告）日：2006-06-29

  The present invention of compounds of formula (I) a stereochemically isomeric form thereof, an N-oxide form thereof or a pharmaceutically acceptable acid addition salt thereof, R 1 and R 2 taken together form a bivalent radical of formula wherein in said bivalent radicals one or two hydrogen atoms may be substituted with C 1-6 alkyl; R 3 is hydrogen or halo; R 4 is hydrogen or C 1-6 alkyl; R 5 is hydrogen or C 1-6 alkyl; L is C 3-6 cycloalkyl, C 5-6 cycloalkanone, C 2-6 alkenyl, or L is a radical of formula -Alk-R 6 —, Alk-X—R 7 , -Alk-Y—C(═O)—R 9 , or -Alk-Y—C(═O)—NR 11 R 12 wherein each Alk is C 1-12 alkanediyl; and R 6 is hydrogen, cyano, C 1-6 alkylsulfonylamino, C 3-6 cycloalkyl, C 5-6 cycloalkanone, or a heterocyclic ringsystem; R 7 is hydrogen, C 1-6 alkyl, hydroxyC 1-6 alkyl, C 3-6 cycloalkyl, or a heterocyclic ringsystem; X is O, S, SO 2 or NR 8 ; said R 8 being hydrogen or C 1-6 alkyl; R 9 is hydrogen, C 1-6 alkyl, C 3-6 cycloalkyl, C 1-6 alkyloxy or hydroxy; Y is NR 10 or a direct bond; said R 10 being hydrogen, or C 1-6 alkyl; R 11 and R 12 each independently are hydrogen, C 1-6 alkyl, C 3-6 cycloalkyl, or R 11 and R 12 combined with the nitrogen atom may form an optionally substituted pyrrolidinyl, piperidinyl, piperazinyl or 4-morpholinyl ring. Processes for preparing said products, formulations comprising said products and their use as a medicine are disclosed, in particular for treating conditions which are related to impairment of gastric emptying.

  本发明涉及式(I)化合物、其立体化学异构体、N-氧化物形式或其药学上可接受的酸加成盐，其中R1和R2结合形成式的二价基团，其中在所述的二价基团中，一个或两个氢原子可以被C1-6烷基替代；R3为氢或卤素；R4为氢或C1-6烷基；R5为氢或C1-6烷基；L为C3-6环烷基、C5-6环戊酮基、C2-6烯基，或L为式-Alk-R6-、Alk-X-R7、-Alk-Y-C(═O)-R9或-Alk-Y-C(═O)-NR11R12的基团，其中每个Alk为C1-12烷二基；R6为氢、氰基、C1-6烷基磺酰氨基、C3-6环烷基、C5-6环戊酮基或杂环环系统；R7为氢、C1-6烷基、羟基C1-6烷基、C3-6环烷基或杂环环系统；X为O、S、SO2或NR8，其中R8为氢或C1-6烷基；R9为氢、C1-6烷基、C3-6环烷基、C1-6烷氧基或羟基；Y为NR10或直接键，其中R10为氢或C1-6烷基；R11和R12各自独立地为氢、C1-6烷基、C3-6环烷基，或R11和R12与氮原子结合可以形成可选取代的吡咯烷基、哌啶基、哌嗪基或4-吗啉基环。揭示了制备所述产品的方法、包含所述产品的制剂以及其作为药物的用途，特别是用于治疗与胃排空障碍有关的疾病。
• Monocyclic benzamides of 3- or 4-substituted 4-(aminomethyl)-piperidine derivatives
  申请人：——

  公开号：US20030078427A1

  公开（公告）日：2003-04-24

  The present invention of compounds of formula (I) 1 a stereochemically isomeric form thereof, an N-oxide form thereof or a pharmaceutically acceptable acid addition salt thereof, R 1 is C 1-6 alkyloxy, C 2-6 alkenyloxy or C 2-6 alkynyl-oxy; R 2 is hydrogen, C 1-6 alkyl C 1-6 alkyloxy; R 3 is hydrogen or halo; R 4 is hydrogen or C 1-6 alkyl; R 5 is hydrogen or C 1-6 alkyl; L is C 3-6 cycloalkyl, C 5-6 cycloalkanone, C 2-6 alkenyl, or L is a radical of formula-Alk-R 6 —, Alk-X—R 7 , —Alk-Y—C(═O)—R 9 , or —Alk-Y—C(═O)—NR 11 R 12 wherein each Alk is C 1-12 alkanediyl; and R 6 is hydrogen, cyano, C 1-6 alkylsulfonylamino, C 3-6 cycloalkyl, C 5-6 cyclo-alkanone, or a heterocyclic ringsystem; R 7 is hydrogen, C 1-6 alkyl, hydroxyC 1-6 alkyl, C 3-6 cycloalkyl, or a heterocyclic ringsystem; X is O, S, SO 2 or NR 8 ; said R 8 being hydrogen or C 1-6 alkyl; R 9 is hydrogen, C 1-6 alkyl, C 3-6 cycloalkyl, C 1-6 alkyloxy or hydroxy; Y is NR 10 or a direct bond; said R 10 being hydrogen, or C 1-6 alkyl; R 11 and R 12 each independently are hydrogen, C 1-6 alkyl, C 3-6 cycloalkyl, or R 11 and R 12 combined with the nitrogen atom may form an optionally substituted pyrrolidinyl, piperidinyl, piperazinyl or 4-morpholinyl ring. Processes for preparing said products, formulations comprising said products and their use as a medicine are disclosed, in particular for treating conditions which are related to impairment of gastric emptying.

  本发明涉及式（I）化合物，其立体化学异构体形式，其N-氧化物形式或其药学上可接受的酸加成盐，其中R1为C1-6烷氧基，C2-6烯氧基或C2-6炔氧基；R2为氢，C1-6烷基或C1-6烷氧基；R3为氢或卤素；R4为氢或C1-6烷基；R5为氢或C1-6烷基；L为C3-6环烷基，C5-6环戊酮，C2-6烯基，或L为式-Alk-R6—，Alk-X—R7，—Alk-Y—C(═O)—R9或—Alk-Y—C(═O)—NR11R12的基团，其中每个Alk为C1-12烷二基；R6为氢，氰基，C1-6烷基磺酰氨基，C3-6环烷基，C5-6环戊酮或杂环环系；R7为氢，C1-6烷基，羟基C1-6烷基，C3-6环烷基或杂环环系；X为O，S，SO2或NR8；其中R8为氢或C1-6烷基；R9为氢，C1-6烷基，C3-6环烷基，C1-6烷氧基或羟基；Y为NR10或直接键；其中R10为氢或C1-6烷基；R11和R12各自独立地为氢，C1-6烷基，C3-6环烷基，或R11和R12与氮原子结合可以形成可选择取代的吡咯烷基，哌啶基，哌嗪基或4-吗啉基环。公开了制备所述产品的过程，包含所述产品的配方以及其作为药物的用途，特别是用于治疗与胃排空障碍有关的疾病。
• Gastrokinetic monocyclic benzamides of 3-or 4-substituted 4-(aminoethyl)-piperidine derivatives
  申请人：Janssen Pharmaceutics, N.V.

  公开号：US06750349B2

  公开（公告）日：2004-06-15

  The present invention of compounds of formula (I) a stereochemically isomeric form thereof, an N-oxide form thereof or a pharmaceutically acceptable acid addition salt thereof, R1 is C1-6alkyloxy, C2-6alkenyloxy or C2-6alkynyl-oxy; R2 is hydrogen, C1-6alkyl C1-6alkyloxy; R3 is hydrogen or halo; R4 is hydrogen or C1-6alkyl; R5 is hydrogen or C1-6alkyl; L is C3-6cycloalkyl, C5-6cycloalkanone, C2-6alkenyl, or L is a radical of formula —Alk—R6—, Alk-X—R7, —Alk—Y—C(═O)—R9, or —Alk—Y—C(═O)—NR11R12 wherein each Alk is C1-12alkanediyl; and R6 is hydrogen, cyano, C1-6alkylsulfonylamino, C3-6cycloalkyl, C5-6cycloalkanone, or a heterocyclic ringsystem; R7 is hydrogen, C1-6alkyl, hydroxyC1-6alkyl, C3-6cycloalkyl, or a heterocyclic ringsystem; X is O, S, SO2 or NR8; said R8 being hydrogen or C1-6alkyl; R9 is hydrogen, C1-6alkyl, C3-6cycloalkyl, C1-6alkyloxy or hydroxy; Y is NR10 or a direct bond; said R10 being hydrogen, or C1-6alkyl; R11 and R12 each independently are hydrogen, C1-6alkyl, C3-6cycloalkyl, or R11 and R12 combined with the nitrogen atom may form an optionally substituted pyrrolidinyl, piperidinyl, piperazinyl or 4-morpholinyl ring. Processes for preparing said products, formulations comprising said products and their use as a medicine are disclosed, in particular for treating conditions which are related to impairment of gastric emptying.

  本发明涉及公式(I)的化合物及其立体化学异构体，N-氧化物形式或其药学上可接受的酸加成盐，其中R1为C1-6烷氧基，C2-6烯氧基或C2-6炔基氧基；R2为氢，C1-6烷基或C1-6烷氧基；R3为氢或卤素；R4为氢或C1-6烷基；R5为氢或C1-6烷基；L为C3-6环烷基，C5-6环戊酮，C2-6烯基，或L为公式-Alk-R6-，Alk-X-R7，-Alk-Y-C（═O）-R9或-Alk-Y-C（═O）-NR11R12的基团，其中每个Alk为C1-12烷二基；R6为氢，氰基，C1-6烷基磺酰氨基，C3-6环烷基，C5-6环戊酮或杂环环系；R7为氢，C1-6烷基，羟基C1-6烷基，C3-6环烷基或杂环环系；X为O，S，SO2或NR8；其中R8为氢或C1-6烷基；R9为氢，C1-6烷基，C3-6环烷基，C1-6烷氧基或羟基；Y为NR10或直接键；其中R10为氢或C1-6烷基；R11和R12各自独立地为氢，C1-6烷基，C3-6环烷基，或R11和R12与氮原子结合可形成可选取代的吡咯烷基，哌啶基，哌嗪基或4-吗啉基环。本发明还揭示了制备上述产品的过程，包括包含上述产品的制剂以及其作为药物的用途，特别是用于治疗与胃排空障碍有关的疾病。