(S)-3,4,5,6-tetrahydro-5-methylamino-2-ureidopyrimidin-4-one | 765299-25-0

• 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: (S)-3,4,5,6-tetrahydro-5-methylamino-2-ureidopyrimidin-4-one
• 英文别名: [(5S)-5-(methylamino)-6-oxo-4,5-dihydro-1H-pyrimidin-2-yl]urea
• CAS: 765299-25-0
• 化学式: C₆H₁₁N₅O₂
• 分子量: 185.186
• InChiKey: YZYUOXBMEKWXLI-VKHMYHEASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.3
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  109
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-3,4,5,6-tetrahydro-5-methylamino-2-ureidopyrimidin-4-one 在 氢气 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 palladium dichloride 作用下， 以 甲醇 、 N,N-二甲基乙酰胺 为溶剂， 反应 4.5h， 生成 TAN-1057A dihydrochloride
  参考文献：
  名称：

  First enantioselective synthesis of the novel antiinfective TAN-1057A via its aminomethyl-substituted dihydropyrimidinone heterocycle

  摘要：

  Enantiomerically pure N-2-Z-N-2-MeAsnOH [(S)-14], prepared in 8 steps (23% overall yield) from asparaginic acid, was first subjected to a Hofmann degradation with PhI(OCOCF3)(2) yielding (S)-N-2-Z-N-2-methyl-2,3-diaminopropanoic acid [N-2-Z-N-2-Me-L-A(2)pr, (S)-15], and this in turn was protected to give N-2-Z-N-3-Boc-N-2-Me-L-A(2)pr [(S)-17]. Condensation of (S)-17 with HN=C(SMe)NHCONH2 followed by removal of the tert-butoxycarbonyl protecting group, cyclization and hydrogenolytic removal of the Z-group gave the heterocycle of TAN-1057A [(S)-1] with an e.e. of 87 in 36% yield [from (S)-14]. Coupling of (S)-1 with (S)-tris-Z-beta-homoarginine (20a) in the presence of O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (HATU) and iPr(2)NEt in N,N-dimethyl-acetamide followed by hydrogenolysis afforded the most active A-diastereomer of the natural antibiotic TAN-1057 in 52% yield (from (S)-1 and 20a). Similarly, starting from (S)-1, a single diastereomer of the potent, less toxic TAN-1057A analogue 22b with a beta-lysine side chain has been prepared. All described synthetic steps do not require column chromatography for purification of the products. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2004.06.034
• 作为产物：
  描述：

  benzyl N-[(2S)-1-[[(Z)-N-carbamoyl-C-methylsulfanylcarbonimidoyl]amino]-3-[(2-methylpropan-2-yl)oxycarbonylamino]-1-oxopropan-2-yl]-N-methylcarbamate 在 palladium on activated charcoal 三氟乙酸 、 溶剂黄146 、 三乙胺 、 氢气 作用下， 以 二氯甲烷 、 苯甲醚 、 N,N-二甲基乙酰胺 为溶剂， 反应 4.0h， 生成 (R)-3,4,5,6-tetrahydro-5-methylamino-2-ureidopyrimidin-4-one 、 (S)-3,4,5,6-tetrahydro-5-methylamino-2-ureidopyrimidin-4-one
  参考文献：
  名称：

  First enantioselective synthesis of the novel antiinfective TAN-1057A via its aminomethyl-substituted dihydropyrimidinone heterocycle

  摘要：

  Enantiomerically pure N-2-Z-N-2-MeAsnOH [(S)-14], prepared in 8 steps (23% overall yield) from asparaginic acid, was first subjected to a Hofmann degradation with PhI(OCOCF3)(2) yielding (S)-N-2-Z-N-2-methyl-2,3-diaminopropanoic acid [N-2-Z-N-2-Me-L-A(2)pr, (S)-15], and this in turn was protected to give N-2-Z-N-3-Boc-N-2-Me-L-A(2)pr [(S)-17]. Condensation of (S)-17 with HN=C(SMe)NHCONH2 followed by removal of the tert-butoxycarbonyl protecting group, cyclization and hydrogenolytic removal of the Z-group gave the heterocycle of TAN-1057A [(S)-1] with an e.e. of 87 in 36% yield [from (S)-14]. Coupling of (S)-1 with (S)-tris-Z-beta-homoarginine (20a) in the presence of O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (HATU) and iPr(2)NEt in N,N-dimethyl-acetamide followed by hydrogenolysis afforded the most active A-diastereomer of the natural antibiotic TAN-1057 in 52% yield (from (S)-1 and 20a). Similarly, starting from (S)-1, a single diastereomer of the potent, less toxic TAN-1057A analogue 22b with a beta-lysine side chain has been prepared. All described synthetic steps do not require column chromatography for purification of the products. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2004.06.034

文献信息

• TAN-1057 DERIVATE
  申请人：Bayer Aktiengesellschaft

  公开号：EP1117652A1

  公开（公告）日：2001-07-25
• US6617332B1
  申请人：——

  公开号：US6617332B1

  公开（公告）日：2003-09-09
• [DE] TAN-1057 DERIVATE<br/>[EN] TAN-1057 DERIVATIVES<br/>[FR] DERIVES DE TAN 1057
  申请人：BAYER AG

  公开号：WO2000012484A1

  公开（公告）日：2000-03-09

  Die Erfindung betrifft neue Naturstoffderivate, Verfahren zu ihrer Herstellung, sie umfassende pharmazeutische Zusammensetzungen sowie ihre Verwendung bei der Behandlung von Erkrankungen bei Menschen oder Tieren.
• First enantioselective synthesis of the novel antiinfective TAN-1057A via its aminomethyl-substituted dihydropyrimidinone heterocycle
  作者：Vladimir N. Belov、Michael Brands、Siegfried Raddatz、Jochen Krüger、Sofia Nikolskaya、Viktor Sokolov、Armin de Meijere

  DOI：10.1016/j.tet.2004.06.034

  日期：2004.8

  Enantiomerically pure N-2-Z-N-2-MeAsnOH [(S)-14], prepared in 8 steps (23% overall yield) from asparaginic acid, was first subjected to a Hofmann degradation with PhI(OCOCF3)(2) yielding (S)-N-2-Z-N-2-methyl-2,3-diaminopropanoic acid [N-2-Z-N-2-Me-L-A(2)pr, (S)-15], and this in turn was protected to give N-2-Z-N-3-Boc-N-2-Me-L-A(2)pr [(S)-17]. Condensation of (S)-17 with HN=C(SMe)NHCONH2 followed by removal of the tert-butoxycarbonyl protecting group, cyclization and hydrogenolytic removal of the Z-group gave the heterocycle of TAN-1057A [(S)-1] with an e.e. of 87 in 36% yield [from (S)-14]. Coupling of (S)-1 with (S)-tris-Z-beta-homoarginine (20a) in the presence of O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (HATU) and iPr(2)NEt in N,N-dimethyl-acetamide followed by hydrogenolysis afforded the most active A-diastereomer of the natural antibiotic TAN-1057 in 52% yield (from (S)-1 and 20a). Similarly, starting from (S)-1, a single diastereomer of the potent, less toxic TAN-1057A analogue 22b with a beta-lysine side chain has been prepared. All described synthetic steps do not require column chromatography for purification of the products. (C) 2004 Elsevier Ltd. All rights reserved.