(S)-(+)-2-羟基-5,5-二甲基-4-苯基-1,3,2-二噁磷己环2-氧化物 | 98674-81-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: (S)-(+)-2-羟基-5,5-二甲基-4-苯基-1,3,2-二噁磷己环2-氧化物
• 中文别名: 贝达喹啉中间体E
• 英文名称: (S)-(+)-5,5-dimethyl-2-hydroxy-4-phenyl-1,3,2-dioxaphosphorinane 2-oxide
• 英文别名: (S)-(+)-5,5-dimethyl-2-hydroxy-4-phenyl-1,3,2-dioxaphosphorinane-2-oxide；(+)-(S)-2-hydroxy-5,5-dimethyl-4-phenyl-1,3,2-dioxaphosphorinan 2-oxide；(S)-(+)-2-hydroxy-4-(phenyl)-5,5-dimethyl-1,3,2-dioxaphosphinan-2-one；(S)-(+)-1-phenyl-1,3-propanediol-2,2-dimethyl hydrogen phosphate；1,2,3-dioxophosphorinane-5,5-dimethyl-2-hydroxy-4-phenyl-2-oxide；5,5-dimethyl-2-oxo-4-phenyl-[1,3,2]dioxaphosphinan-2-ol；(4S)-2-Hydroxy-5,5-dimethyl-4-phenyl-1,3,2-dioxaphosphinane 2-oxide；(4S)-2-hydroxy-5,5-dimethyl-4-phenyl-1,3,2λ5-dioxaphosphinane 2-oxide
• CAS: 98674-81-8
• 化学式: C₁₁H₁₅O₄P
• 分子量: 242.211
• InChiKey: PSZSDCWNBXVDFG-JTQLQIEISA-N

物化性质

• 熔点：
  223-227 °C(lit.)
• 沸点：
  344.4±45.0 °C(Predicted)
• 密度：
  1.27±0.1 g/cm3(Predicted)
• 稳定性/保质期：
  如果按照规定使用和储存，则不会发生分解，没有已知的危险反应，应避免与强氧化剂接触。

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 危险品标志：
  Xi
• 危险类别码：
  R36/37/38
• 海关编码：
  2934999090
• 安全说明：
  S26,S36
• 储存条件：
  请将贮藏器密封，并将其存放在阴凉、干燥处。确保工作环境具有良好的通风或排气设施。

反应信息

• 作为反应物：
  描述：

  (2R)-2-(4-chlorophenyl)-4,4-dimethylpyrrolidine 、 (S)-(+)-2-羟基-5,5-二甲基-4-苯基-1,3,2-二噁磷己环2-氧化物 以 乙酸乙酯 、 异丙醇 为溶剂， 生成 (4S)-2-hydroxy-5,5-dimethyl-4-phenyl-1,3,2-dioxaphosphinane 2-oxide compound with (R)-2-(4-chlorophenyl)-4,4-dimethylpyrrolidine (1:1)
  参考文献：
  名称：

  Novel 3-O-carbamoyl erythromycin A derivatives (carbamolides) with activity against resistant staphylococcal and streptococcal isolates

  摘要：

  A novel series of 3-O-carbamoyl erythromycin A derived analogs, labeled carbamolides, with activity versus resistant bacterial isolates of staphylococci (including macrolide and oxazolidinone resistant strains) and streptococci are reported. An (R)-2-aryl substituent on a pyrrolidine carbamate appeared to be critical for achieving potency against resistant strains. Crystal structures showed a distinct aromatic interaction between the (R)-2-aryl (3-pyridyl for 4d) substituent on the pyrrolidine and G2484 (G2505, Escherichia coli) of the Deinococcus radiodurans 50S ribosome (3.2 angstrom resolution). (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.01.067
• 作为产物：
  描述：

  5,5-dimethyl-2-hydroxy-4-phenyl-1,3,2-dioxaphosphorinane 2-oxide 生成 (S)-(+)-2-羟基-5,5-二甲基-4-苯基-1,3,2-二噁磷己环2-氧化物
  参考文献：
  名称：

  The design of resolving agents. Chiral cyclic phosphoric acids

  摘要：

  DOI：

  10.1021/jo00223a018
• 作为试剂：
  描述：

  (3,5-dimethylphenyl)(pyridin-2-yl)methanol 在 N-甲基吗啉 、 2-氯-4,6-二甲氧基-1,3,5-三嗪 、 硫酸 、 palladium on activated charcoal 、 氢气 、 (S)-(+)-2-羟基-5,5-二甲基-4-苯基-1,3,2-二噁磷己环2-氧化物 作用下， 以 四氢呋喃 、 甲醇 、 水 、 异丙醇 为溶剂， 50.0 ℃ 、310.27 kPa 条件下， 反应 9.0h， 生成 (4S)-6-{2-[(2R)-2-(3,5-dimethylbenzyl)piperidin-1-yl]-2-oxoethyl}-4-(1H-indazol-3-ylmethyl)-1-phenyl-4H-[1,2,4]triazolo[4,3-a][1,5]benzodiazepin-5(6H)-one
  参考文献：
  名称：

  Discovery of new piperidine amide triazolobenzodiazepinones as intestinal-selective CCK1 receptor agonists

  摘要：

  New cholecystokinin-1 receptor (CCK1R) agonist 'triggers' were identified using iterative library synthesis. Structural activity relationship studies led to the discovery of compound 10e, a potent CCK1R agonist that demonstrated robust weight loss in a diet-induced obese rat model with very low systemic exposure. Pharmacokinetic data suggest that efficacy is primarily driven through activation of CCK1R's located within the intestinal wall. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.02.049

文献信息

• Synthesis of Enantiopure 1-Aryl-1-butylamines and 1-Aryl-3-butenylamines by Diastereoselective Addition of Allylzinc Bromide to Imines Derived from (R)-Phenylglycine Amide
  作者：Jan Dalmolen、Marcel van der Sluis、José W. Nieuwenhuijzen、Auke Meetsma、Ben de Lange、Bernard Kaptein、Richard M. Kellogg、Quirinus B. Broxterman

  DOI：10.1002/ejoc.200300662

  日期：2004.4

  The highly diastereoselective addition of allylzinc bromide to imines derived from (R)-phenylglycine amide is reported. Homoallylamines with high enantiomeric purity are obtained from the adducts in three steps on removal of the chiral auxiliary by means of a nonreductive protocol. Removal of the auxiliary by hydrogenation leads to the saturated amines, also in high enantiomeric purity. [reaction: see

  据报道，烯丙基溴化锌以高度非对映选择性加成到衍生自 (R)-苯基甘氨酸酰胺的亚胺中。具有高对映体纯度的高烯丙基胺通过非还原性方案在去除手性助剂的三个步骤中从加合物中获得。通过氢化除去助剂产生饱和胺，也具有高对映体纯度。[反应：见正文]
• [EN] (S)-CSA SALT OF S-KETAMINE, (R)-CSA SALT OF S-KETAMINE AND PROCESSES FOR THE PREPARATION OF S-KETAMINE<br/>[FR] SEL (S)-CSA DE S-KÉTAMINE, SEL (R)-CSA DE S-KÉTAMINE ET PROCÉDÉS PERMETTANT LA PRÉPARATION DE S-KÉTAMINE
  申请人：CHEN CHENG YI

  公开号：WO2016180984A1

  公开（公告）日：2016-11-17

  The present invention is directed to processes for the preparation of esketamine. The present invention is further directed to processes for the resolution of S-ketamine from a racemic or enantiomerically enriched mixture of ketamine. The present invention is further directed to an (S)-CSA salt of S-ketamine, more particularly a monohydrate form of the (S)-CSA salt of S-ketamine; and to an (R)-CSA salt of R-ketamine.

  本发明涉及制备左旋氯胺酮的方法。本发明进一步涉及从消旋或对映体富集混合物中分离S-氯胺酮的方法。本发明还涉及S-氯胺酮的(S)-CSA盐，更具体地是(S)-CSA盐的单水合物形式；以及R-氯胺酮的(R)-CSA盐。
• Four-component α-bromo-β-phosphoalkoxylation of aromatic α,β-unsaturated carbonyl compounds
  作者：Muhammad Sohail、Yixin Zhang、Wujun Liu、Qin Chen、Lei Wang、Zongbao K. Zhao

  DOI：10.1039/c4ra12417k

  日期：——

  Novel α-bromo-β-phosphoalkoxylated carbonyl compounds were produced in moderate to excellent yields via highly selective four-component reaction involving NBS, a cyclic ether, an organic phosphate and an aromatic α,β-unsaturated carbonyl compound.

  通过高度选择性的四组分反应，使用NBS、环醚、有机磷酸酯和芳香族α,β-不饱和羰基化合物，制备了产率在中等到优良之间的新颖α-溴-β-磷醚基羰基化合物。
• [EN] TRICYCLIC 1-[(3-INDOL-3-YL)CARBONYL] PIPERAZINE DERIVATIVES AS CANNABINOID CB1 RECEPTOR AGONISTS<br/>[FR] DERIVES TRICYCLIQUES DE PIPERAZINE 1-[(3-INDOL-3-YL)CARBONYL] UTILES EN TANT QU'AGONISTES DU RECEPTEUR CANNABINOIDE CB1
  申请人：AKZO NOBEL NV

  公开号：WO2005058327A1

  公开（公告）日：2005-06-30

  The invention relates to tricyclic 1-[(indol-3-yl)carbonyl]piperazine derivative having the general Formula (I) wherein X is CH2, O or S; R represents 1-3 substituents independently selected from H, (C1-4)alkyl, (C1-4)alkyloxy and halogen; R1 is (C5-8)cycloalkyl; R2 is H or (C1-4)alkyl; R3, R3´, R4’ R4’, R5, R5’ and R6’ are independently hydrogen or (C1-4)-alkyl, optionally substituted with (C1-4)alkyloxy, OH or halogen; R6 is hydrogen or (C1-4)alkyl, optionally substituted with (C1-4)alkyloxy, OH or halogen; or R6 forms together with R7 a 4-7 membered saturated heterocyclic ring, optionally containing a further heteroatom selected from O and S; R7 forms together with R6 a 4-7 membered saturated heterocydic ring, optionally containing a further heteroatom selected from O and S; or R7 is H, (C1-4)alkyl or (C3-5)cycloalkyl, the alkyl groups being optionally substituted with OH, halogen or (C1-4)alkyloxy; or a pharmaceutically acceptable salt thereof. The invention also relates to pharmaceutical compositions comprising said tricyclic 1-[(indol-3-yl)carbonyl]piperazine derivatives, and to the use of these derivatives in the treatment of pain, such as peri-operative pain, chronic pain neuropathic pain, cancer pain, and pain and spasticity associated with multiple sclerosis.

  该发明涉及具有通式（I）的三环1-[(吲哚-3-基)羰基]哌嗪衍生物，其中X为CH2、O或S；R代表1-3个取自H、(C1-4)烷基、(C1-4)烷氧基和卤素的取代基；R1为(C5-8)环烷基；R2为H或(C1-4)烷基；R3、R3'、R4'、R4'、R5、R5'和R6'独立地为氢或(C1-4)烷基，可选地取代为(C1-4)烷氧基、OH或卤素；R6为氢或(C1-4)烷基，可选地取代为(C1-4)烷氧基、OH或卤素；或R6与R7一起形成一个含有O和S等进一步杂原子的4-7元饱和杂环；R7与R6一起形成一个含有O和S等进一步杂原子的4-7元饱和杂环；或R7为H、(C1-4)烷基或(C3-5)环烷基，烷基基团可选地取代为OH、卤素或(C1-4)烷氧基；或其药学上可接受的盐。该发明还涉及包含所述三环1-[(吲哚-3-基)羰基]哌嗪衍生物的药物组合物，并且涉及在治疗疼痛，如围手术疼痛、慢性疼痛、神经痛、癌症疼痛以及与多发性硬化相关的疼痛和痉挛中使用这些衍生物。
• Bromophosphoalkoxylation of olefins with organic phosphates, cyclic ethers and NBS
  作者：Muhammad Sohail、Chang Peng、Siyang Ning、Yixin Zhang、Muhammad Khan、Zongbao K. Zhao

  DOI：10.1016/j.tet.2015.12.008

  日期：2016.2

  A variety of structurally novel phosphoalkoxy ester derivatives were prepared via highly regio- and diastereoselective four-component reaction involving olefin, cyclic ether, halogen reagent and organic phosphate. All components can be varied flexibly and moderate to excellent yields were obtained at room temperature. Several of these ester derivatives showed strong anticancer activity against human

  通过高度区域选择性和非对映选择性的四组分反应，包括烯烃，环醚，卤素试剂和有机磷酸酯，制备了多种结构新颖的磷酸烷氧基酯衍生物。所有组分均可灵活变化，在室温下可获得中等至极好的收率。这些酯衍生物中的几种显示出对人肺腺癌细胞的强抗癌活性。