[(S)-1-((R)-1-Hydroxy-ethyl)-butyl]-carbamic acid tert-butyl ester | 599207-03-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: [(S)-1-((R)-1-Hydroxy-ethyl)-butyl]-carbamic acid tert-butyl ester
• 英文别名: tert-butyl N-[(2R,3S)-2-hydroxyhexan-3-yl]carbamate
• CAS: 599207-03-1
• 化学式: C₁₁H₂₃NO₃
• 分子量: 217.309
• InChiKey: YPDFDUAAFOWUDT-BDAKNGLRSA-N

物化性质

• 沸点：
  319.3±25.0 °C(Predicted)
• 密度：
  0.984±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  15
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  58.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  [(S)-1-((R)-1-Hydroxy-ethyl)-butyl]-carbamic acid tert-butyl ester 在 盐酸 、 三乙胺 、 calcium carbonate 作用下， 以 乙醇 、 二氯甲烷 、 氯仿 、 水 为溶剂， 生成 2-isothiocyanato-1-methylpentyl methanesulfonate
  参考文献：
  名称：

  4,5-Dialkylsubstituted 2-imino-1,3-thiazolidine derivatives as potent inducible nitric oxide synthase inhibitors

  摘要：

  In the course of our search for selective iNOS inhibitors, we have previously reported that 2-imino-1,3-oxazolidine derivatives (1) and 2-aminothiazole derivatives (2) are selective iNOS inhibitors. In order to find more potent iNOS inhibitors, we focused our efforts on the synthesis and evaluation of the inhibitory activity against iNOS and selectivity for iNOS both in vitro and in vivo of a series of 2-imino-1,3-thiazolidine derivatives (3), which are analogues of I and 2. Our results show that among the compounds synthesized (4R,5R)-5-ethyl-2-imino-4-methyl-1,3-thiazolidine [(4R,5R)-14a: ES-1537] exhibited potent inhibitory activity and selectivity for iNOS. In addition, ES-1537 had good pharmacokinetic profile in rats with BA value of 80%. It is therefore expected that ES-1537 may be therapeutically useful for the treatment of diseases related to excess production of NO. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.05.031
• 作为产物：
  描述：

  (S)-2-(N,N-Dibenzylamino)-pentanal 在 palladium dihydroxide 氢气 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 生成 [(S)-1-((R)-1-Hydroxy-ethyl)-butyl]-carbamic acid tert-butyl ester
  参考文献：
  名称：

  4,5-Dialkylsubstituted 2-imino-1,3-thiazolidine derivatives as potent inducible nitric oxide synthase inhibitors

  摘要：

  In the course of our search for selective iNOS inhibitors, we have previously reported that 2-imino-1,3-oxazolidine derivatives (1) and 2-aminothiazole derivatives (2) are selective iNOS inhibitors. In order to find more potent iNOS inhibitors, we focused our efforts on the synthesis and evaluation of the inhibitory activity against iNOS and selectivity for iNOS both in vitro and in vivo of a series of 2-imino-1,3-thiazolidine derivatives (3), which are analogues of I and 2. Our results show that among the compounds synthesized (4R,5R)-5-ethyl-2-imino-4-methyl-1,3-thiazolidine [(4R,5R)-14a: ES-1537] exhibited potent inhibitory activity and selectivity for iNOS. In addition, ES-1537 had good pharmacokinetic profile in rats with BA value of 80%. It is therefore expected that ES-1537 may be therapeutically useful for the treatment of diseases related to excess production of NO. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.05.031

文献信息

• Process for preparing purine derivatives
  申请人：Cyclacel Limited

  公开号：US10927113B2

  公开（公告）日：2021-02-23

  The present invention relates to a process for preparing a compound of formula [I], said process comprising the steps of: formula [II]+formula [III]→formula [I] (i) forming a reaction mixture comprising (a) a compound of formula [II], (b) a compound of formula [III] and (c) 1,2-propanediol or polyethylene glycol, or a mixture thereof, and optionally (d) a base; (ii) heating said reaction mixture to a temperature of at least about 150° C. to form a compound of formula [I]; (iii) isolating said compound of formula [I]; and (iv) optionally converting said compound of formula [I] into salt form; wherein: R1 and R2 are each independently H, alkyl or haloalkyl; R3 and R4 are each independently H, alkyl, haloalkyl or aryl; R5 is alkyl, alkenyl, cycloalkyl or cycloalkyl-alkyl, each of which may be optionally substituted with one or more OH groups; R6 is selected from cyclopropylamino, cyclopropylmethylamino, cyclobutylamino, cyclobutylmethylamino and formula (A) where one of X, Y and Z is N and the remainder are CR9; R7, R8 and each R9 are independently H, alkyl or haloalkyl, wherein at least one of R7, R8 and R9 is other than H. Further aspects of the invention relate to a highly diastereoselective process for the preparation of compounds of formula [III], a process for preparing intermediates of formula [II], and other intermediates useful in the synthesis of compounds of formula [I], and to a process for preparing the crystalline tartrate salt and free base of compounds of formula [I].

  本发明涉及一种制备式[I]化合物的工艺，所述工艺包括以下步骤： 式[II]+式[III]→式[I] (i) 形成反应混合物，所述反应混合物包括(a)式[II]化合物、(b)式[III]化合物和(c)1,2-丙二醇或聚乙二醇或其混合物，以及任选的(d)碱； (ii) 将所述反应混合物加热至至少约 150°C 的温度，以形成式[I]化合物； (iii) 分离所述式[I]化合物；以及 (iv) 任选地将所述式[I]化合物转化为盐形式； 其中(iii) 分离所述式[I]化合物；以及 (iv) 可选地将所述式[I]化合物转化为盐形式； 其中：R1 和 R2 各自独立地为 H、烷基或卤代烷基； R3 和 R4 各自独立地为 H、烷基、卤代烷基或芳基； R5 为烷基、烯基、环烷基或环烷基-烷基，其中每个环烷基可任选被一个或多个 OH 基团取代；R6选自环丙基氨基、环丙基甲基氨基、环丁基氨基、环丁基甲基氨基和式(A)，其中X、Y和Z之一为N，其余为CR9；R7、R8和每个R9独立地为H、烷基或卤代烷基，其中R7、R8和R9中至少有一个不是H。本发明的其它方面涉及制备式[III]化合物的高非对映选择性工艺、制备式[II]中间体和其它用于合成式[I]化合物的中间体的工艺，以及制备式[I]化合物的酒石酸盐结晶和游离碱的工艺。
• 4,5-Dialkylsubstituted 2-imino-1,3-thiazolidine derivatives as potent inducible nitric oxide synthase inhibitors
  作者：Shigeo Ueda、Hideo Terauchi、Akihiro Yano、Masashi Matsumoto、Taeko Kubo、Yoko Kyoya、Kenji Suzuki、Motoharu Ido、Motoji Kawasaki

  DOI：10.1016/j.bmc.2004.05.031

  日期：2004.8.1

  In the course of our search for selective iNOS inhibitors, we have previously reported that 2-imino-1,3-oxazolidine derivatives (1) and 2-aminothiazole derivatives (2) are selective iNOS inhibitors. In order to find more potent iNOS inhibitors, we focused our efforts on the synthesis and evaluation of the inhibitory activity against iNOS and selectivity for iNOS both in vitro and in vivo of a series of 2-imino-1,3-thiazolidine derivatives (3), which are analogues of I and 2. Our results show that among the compounds synthesized (4R,5R)-5-ethyl-2-imino-4-methyl-1,3-thiazolidine [(4R,5R)-14a: ES-1537] exhibited potent inhibitory activity and selectivity for iNOS. In addition, ES-1537 had good pharmacokinetic profile in rats with BA value of 80%. It is therefore expected that ES-1537 may be therapeutically useful for the treatment of diseases related to excess production of NO. (C) 2004 Elsevier Ltd. All rights reserved.