N~1~-[(10S)-2-{[(4-Fluorophenyl)methyl]carbamoyl}-3-hydroxy-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-a]azepin-10-yl]-N~1~,N~2~,N~2~-trimethylethanediamide | 724444-40-0

• 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: N~1~-[(10S)-2-{[(4-Fluorophenyl)methyl]carbamoyl}-3-hydroxy-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-a]azepin-10-yl]-N~1~,N~2~,N~2~-trimethylethanediamide
• 英文别名: N'-[(10S)-2-[(4-fluorophenyl)methylcarbamoyl]-3-hydroxy-4-oxo-7,8,9,10-tetrahydro-6H-pyrimido[1,2-a]azepin-10-yl]-N,N,N'-trimethyloxamide
• CAS: 724444-40-0
• 化学式: C₂₂H₂₆FN₅O₅
• 分子量: 459.477
• InChiKey: WBQCKUNNRLRPOG-HNNXBMFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  33
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  123
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  [(10S)-10-[[2-(dimethylamino)-2-oxoacetyl]-methylamino]-2-[(4-fluorophenyl)methylcarbamoyl]-4-oxo-7,8,9,10-tetrahydro-6H-pyrimido[1,2-a]azepin-3-yl] methanesulfonate 在 二甲胺 作用下， 以 四氢呋喃 为溶剂， 以24.2 g的产率得到N~1~-[(10S)-2-{[(4-Fluorophenyl)methyl]carbamoyl}-3-hydroxy-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-a]azepin-10-yl]-N~1~,N~2~,N~2~-trimethylethanediamide
  参考文献：
  名称：

  HIV整合酶抑制剂的催化不对称合成

  摘要：

  描述了通过亚胺/烯胺5a - 5b / 5c混合物的独特不对称氢化有效合成HIV整合酶抑制剂（S）-（-）- 1的方​​法。Rh（I）-Josiphos络合物对亚胺/烯胺的氢化反应可得到90％收率和90％ee的收率6。酰胺形成完成的合成1在58％的总收率从2，这是容易获得的由3,4-二氢-2- ħ吡喃在七步序列。氘标记研究表明，不对称氢化主要通过烯胺互变异构体进行。

  DOI：

  10.1021/ol802604v

文献信息

• Synthesis of a hexahydropyrimido[1,2-a]azepine-2-carboxamide derivative useful as an HIV integrase inhibitor
  作者：Marco Ferrara、Benedetta Crescenzi、Monica Donghi、Ester Muraglia、Emanuela Nizi、Silvia Pesci、Vincenzo Summa、Cristina Gardelli

  DOI：10.1016/j.tetlet.2007.09.072

  日期：2007.11

  The hexahydropyrimido[1,2-a]azepine-2-carboxamide derivative 1 could be obtained by three synthetic strategies, which allowed access to multigram amounts of material of high purity and ee. Two strategies involved alternative approaches to the bicyclic pyrimidone core, with the most efficient one being a two-step sequence from commercially available starting materials exploiting a little precedented cyclisation reaction. The remaining steps to 1 included an efficient crystallisation of an intermediate as a single stereoisomer. An alternative strategy employing a chiral starting material led to products of low optical purity but allowed the assignment of the configuration of the stereogenic centre of 1. (c) 2007 Elsevier Ltd. All rights reserved.
• [EN] PROCESS FOR PREPARING HEXAHYDROPYRIMIDO[1,2-A]AZEPINE-2-CARBOXYLATES AND RELATED COMPOUNDS<br/>[FR] PROCEDE DE PREPARATION DE HEXAHYDROPYRIMIDO[1,2-A]AZEPINE-2-CARBOXYLATES ET COMPOSES CONNEXES
  申请人：MERCK & CO INC

  公开号：WO2005061501A3

  公开（公告）日：2006-04-06
• Catalytic Asymmetric Synthesis of an HIV Integrase Inhibitor
  作者：Yong-Li Zhong、Shane W. Krska、Hua Zhou、Robert A. Reamer、Jaemoon Lee、Yongkui Sun、David Askin

  DOI：10.1021/ol802604v

  日期：2009.1.15

  An efficient synthesis of HIV integrase inhibitor (S)-(−)-1 via a unique asymmetric hydrogenation of a mixture of imines/enamine 5a−5b/5c is described. Hydrogenation of the imines/enamine by a Rh(I)−Josiphos complex afforded 6 in 90% yield and 90% ee. Amide formation completed the synthesis of 1 in 58% overall yield from 2, which is readily available from 3,4-dihydro-2H-pyran in a seven-step sequence

  描述了通过亚胺/烯胺5a - 5b / 5c混合物的独特不对称氢化有效合成HIV整合酶抑制剂（S）-（-）- 1的方​​法。Rh（I）-Josiphos络合物对亚胺/烯胺的氢化反应可得到90％收率和90％ee的收率6。酰胺形成完成的合成1在58％的总收率从2，这是容易获得的由3,4-二氢-2- ħ吡喃在七步序列。氘标记研究表明，不对称氢化主要通过烯胺互变异构体进行。