(R)-(-)-2-amino-4-hydroxy-6-[2-(4-bromophenyl)ethyl]-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶并嘧啶类
• 英文名称: (R)-(-)-2-amino-4-hydroxy-6-[2-(4-bromophenyl)ethyl]-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidine
• 英文别名: (6R)-2-amino-6-[2-(4-bromophenyl)ethyl]-5,6,7,8-tetrahydro-3H-pyrido[2,3-d]pyrimidin-4-one
• 化学式: C₁₅H₁₇BrN₄O
• 分子量: 349.23
• InChiKey: AWOVINGGMOSUSP-SNVBAGLBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  79.5
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (R)-(-)-2-amino-4-hydroxy-6-[2-(4-bromophenyl)ethyl]-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidine 在 N-甲基吗啉 、 N-甲基吡咯烷酮 、 盐酸 、 potassium cyanide 、 sodium hydroxide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 76.0h， 生成 洛美曲索
  参考文献：
  名称：

  5,10-二氮杂-5,6,7,8-四氢蝶酸和5,10-二氮杂-5,6,7,8-四氢叶酸（DDATHF）的不对称合成和绝对构型

  摘要：

  2-取代的1，3-二醇的脂肪酶催化的对映选择性酯化已用于标题化合物的不对称合成和随后的构型分配中。

  DOI：

  10.1016/s0040-4039(01)93875-4
• 作为产物：
  描述：

  4-溴苯乙醇 在 lithium aluminium tetrahydride 、 sodium azide 、 三丁基膦 、 trimethoxonium tetrafluoroborate 、 sodium hydride 、 溶剂黄146 、 三乙胺 、 sodium iodide 作用下， 以 四氢呋喃 、 乙醚 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 (R)-(-)-2-amino-4-hydroxy-6-[2-(4-bromophenyl)ethyl]-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidine
  参考文献：
  名称：

  5,10-二氮杂-5,6,7,8-四氢蝶酸和5,10-二氮杂-5,6,7,8-四氢叶酸（DDATHF）的不对称合成和绝对构型

  摘要：

  2-取代的1，3-二醇的脂肪酶催化的对映选择性酯化已用于标题化合物的不对称合成和随后的构型分配中。

  DOI：

  10.1016/s0040-4039(01)93875-4

文献信息

• Intermediates for preparing antifolate compounds
  申请人：Eli Lilly and Company

  公开号：US05486614A1

  公开（公告）日：1996-01-23

  This invention relates to intermediates, and processes thereto, for the preparation of tetrahydropyrido[2,3-d]pyrimidines which are useful for the treatment of susceptable neoplasms. The intermediates have the following formula II; ##STR1## wherein the R, R.sup.1 and A groups are as defined in the specification.

  本发明涉及中间体及其制备过程，用于制备四氢吡啶并[2,3-d]嘧啶，该化合物对易感性肿瘤的治疗有用。中间体的化学式为II; ##STR1## 其中R，R.sup.1和A基团如规范中定义。
• Cyclization for preparing antifolate compounds
  申请人：Eli Lilly and Company

  公开号：US05969136A1

  公开（公告）日：1999-10-19

  This invention provides a process for preparing a compound of formula III ##STR1## wherein R.sup.1 is bromo, iodo or COOR.sup.2 ; R.sup.2 is H, C.sub.1 -C.sub.4 alkyl, phenyl which may be substituted or benzyl; and A is a 5- or 6-membered aromatic residue which may contain up to three hetero atoms and which may optionally be substituted with one or two groups selected from the group consisting of halo, hydroxy, C.sub.1 -C.sub.4 alkyl, and C.sub.1 -C.sub.4 alkoxy; or a salt thereof, which comprises (a) reacting a compound of formula I ##STR2## wherein R is C.sub.1 -C.sub.4 alkyl or phenyl which may be substituted; and R.sup.1, R.sup.2, and A are as defined above; or a salt thereof, with a sulfurization agent; (b) cyclizing the reaction product from step (a) with guanidine; and (c) optionally salifying the reaction product from step (b).

  本发明提供了一种制备公式III化合物的方法，其中R.sup.1是溴、碘或COOR.sup.2；R.sup.2是H、C.sub.1-C.sub.4烷基、苯基（可以被取代）或苄基；A是一个含有最多三个杂原子的5-或6-成员芳香残基，可以选用一个或两个从卤素、羟基、C.sub.1-C.sub.4烷基和C.sub.1-C.sub.4烷氧基组成的基团进行取代；或其盐。该方法包括(a)将公式I化合物与硫化剂反应；(b)用脲环化步骤(a)的反应产物；(c)可选地使步骤(b)的反应产物成盐。
• Intermediates for preparing antifolate compounds and processes there to
  申请人：ELI LILLY AND COMPANY

  公开号：EP0593286A2

  公开（公告）日：1994-04-20

  This invention relates to intermediates, and processes thereto, for the preparation of tetrahydropyrido[2,3-d]pyrimidines which are useful for the treatment of susceptable neoplasms.

  本发明涉及用于制备四氢吡啶并[2,3-d]嘧啶的中间体及其工艺。 四氢吡啶并[2,3-d]嘧啶的中间体及其制备方法。
• Asymmetric Synthesis of Lometrexol ((6R)-5,10-Dideaza-5,6,7,8-tetrahydrofolic Acid)
  作者：Charles J. Barnett、Thomas M. Wilson、Samuel R. Wendel、Michael J. Winningham、Jack B. Deeter

  DOI：10.1021/jo00102a031

  日期：1994.11

  An enantioselective synthesis of lometrexol (1) which utilizes (SR)-2-piperidone 18 as a key intermediate is described. Lipase-catalyzed enantioselective esterification of 1,3-propanediol derivative 5 provided (R)-(+)-6, the absolute configuration of which was established by X-ray analysis of the (S)-(alpha-methylbenzyl)carbamate derivative 8. By suitable choice of functional group protection strategies, (R)-(+)-6 could be converted to either enantiomer of azido alcohol 11. The S isomer of 11 was utilized to prepare 18 in three steps. Conversion of 18 to the thiolactam and cyclization with guanidine provided (6R)-5-deaza-5,6,7,8-tetrahydropterin 20. Cyanation of 20 (cuprous cyanide) followed by hydrolysis of the resulting nitrile 21 gave (6R)-5,10-dideaza-5,6,7,8-tetrahydropteroic acid (22). The synthesis of 1 was completed by reaction of 22 with diethyl glutamate via an active ester coupling procedure followed by hydrolysis of the resulting diester.
• Intermediates for preparing antifolate compounds and processes thereto
  申请人：ELI LILLY AND COMPANY

  公开号：EP0593286B1

  公开（公告）日：1999-12-15