3-(1-benzyl-1,2,5,6-tetrahydro-3-pyridyl)-(S)-alanine t-butyl ester | 184879-72-9

• 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: 3-(1-benzyl-1,2,5,6-tetrahydro-3-pyridyl)-(S)-alanine t-butyl ester
• 英文别名: 3-(1-Benzyl-1,2,5,6-tetrahydro-pyridin-3-yl)-(S)-alanine t-butyl ester；tert-butyl (2S)-2-amino-3-(1-benzyl-3,6-dihydro-2H-pyridin-5-yl)propanoate
• CAS: 184879-72-9
• 化学式: C₁₉H₂₈N₂O₂
• 分子量: 316.444
• InChiKey: PHANMECFAQXPJY-KRWDZBQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  23
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  55.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(1-benzyl-1,2,5,6-tetrahydro-3-pyridyl)-(S)-alanine t-butyl ester 、 1,2,3,4-四氢-2-(三氟乙酰基)异喹啉-7-磺酰氯 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 以88%的产率得到N-(2-trifluoroacetyl-1,2,3,4-tetrahydroisoquinoline-7-sulphonyl)-3-(1-benzyl-1,2,5,6-tetrahydro-3-pyridyl)-(S)-alanine t-butyl ester
  参考文献：
  名称：

  Synthesis of 1,2,5,6-Tetrahydro-3-pyridinylalanine: A Key Intermediate in the Preparation of Thrombin Inhibitor UK-239,326

  摘要：

  A short synthesis of N-protected 1,2,5,6-tetrahydro-3-pyridinylalanine derivatives (8-10) was accomplished using a simple procedure of quaternization of (3-pyridyl)alanine 6 with benzyl bromide followed by reduction with NaBH(4). Amino acid 10 was then converted to thrombin inhibitor UK-239,326 (2), which required the sequential functionalization of four amines to give four different functional groups (viz., sulfonamide, carboxamide, guanidine, and methylamine).

  DOI：

  10.1080/00397910701839210
• 作为产物：
  描述：

  N-t-butoxycarbonyl-3-(1-benzyl-1,2,5,6-tetrahydro-3-pyridyl)-(S)-alanine t-butyl ester 在 甲酸 作用下， 以 水 为溶剂， 反应 22.0h， 以70%的产率得到3-(1-benzyl-1,2,5,6-tetrahydro-3-pyridyl)-(S)-alanine t-butyl ester
  参考文献：
  名称：

  Synthesis of 1,2,5,6-Tetrahydro-3-pyridinylalanine: A Key Intermediate in the Preparation of Thrombin Inhibitor UK-239,326

  摘要：

  A short synthesis of N-protected 1,2,5,6-tetrahydro-3-pyridinylalanine derivatives (8-10) was accomplished using a simple procedure of quaternization of (3-pyridyl)alanine 6 with benzyl bromide followed by reduction with NaBH(4). Amino acid 10 was then converted to thrombin inhibitor UK-239,326 (2), which required the sequential functionalization of four amines to give four different functional groups (viz., sulfonamide, carboxamide, guanidine, and methylamine).

  DOI：

  10.1080/00397910701839210

文献信息

• ANTITHROMBOTIC AMIDINOTETRAHYDROPYRIDYLALANINE DERIVATIVES
  申请人：Pfizer Research and Development Company, N.V./S.A.

  公开号：EP0822934A1

  公开（公告）日：1998-02-11
• US5798352A
  申请人：——

  公开号：US5798352A

  公开（公告）日：1998-08-25
• [EN] ANTITHROMBOTIC AMIDINOTETRAHYDROPYRIDYLALANINE DERIVATIVES<br/>[FR] DERIVES D'AMIDINOTETRAHYDROPYRIDYLALANINE PRESENTANT UNE ACTIVITE ANTITHROMBOTIQUE
  申请人：PFIZER RESEARCH AND DEVELOPMENT COMPANY, N.V./S.A.

  公开号：WO1996033993A1

  公开（公告）日：1996-10-31

  (EN) Compounds of formula (I), pharmaceutically acceptable salts thereof, and pharmaceutically acceptable solvates of either entity, wherein Y is optionally monounsaturated C3-C5 alkylene optionally substituted with C1-C4 alkyl or methylene; R1 is H; C1-C4 alkyl optionally substituded with C1-C4 alkoxy, OH, NR5R6, CONR5R6, C3-C6 cycloalkyl or aryl; or C3-C6 alkenyl; R2 is H; C1-C4 alkyl optionally substituted with C1-C4 alkoxy, OH, NR5R6, CONR5R6, C3-C6 cycloalkyl or aryl; or CONR5R6; R3 and R4 are each independently selected from H; C1-C4 alkyl optionally substituded with NR5R6; C1-C4 alkoxy; halo; CONR5R6 and aryl; aryl is phenyl optionally substituted with one, two or three substituents independently selected from C1-C4 alkyl, C1-C4 alkoxy, OH, halo and CF3; R5 and R6 are each independently selected from H and C1-C4 alkyl; and m and n are each independently 1, 2 or 3; are potent and selective thrombin inhibitors useful in the treatment of, $i(inter alia), deep vein thrombosis; reocclusion following thrombolytic therapy; chronic arterial obstruction; peripheral vascular disease; acute myocardial infarction; unstable angina; atrial fibrillation; thrombotic stroke; transient ischaemic attacks; restenosis and occlusion following angioplasty; or neurodegenerative disorders.(FR) Composés de la formule (I), leurs sels acceptables sur le plan pharmacologique, ainsi que des solvates de ces composés ou sels, également acceptables sur le plan pharmacologique. Dans cette formule, Y représente alkylène C3-C5 mono-insaturé, éventuellement substitué par alkyle C1-C4 ou méthylène; R1 représente H, alkyle C1-C4 éventuellement substitué par alcoxy C1-C4, par OH, NR5R6, CONR5R6, cycloalkyle C3-C6 ou aryle; ou alcényle C3-C6; R2 représente H, alkyle C1-C4 éventuellement substitué par alcoxy C1-C4, par OH, NR5R6, CONR5R6, cycloalkyle C3-C6 ou aryle; ou CONR5R6; R3 et R4 sont choisis chacun indépendamment parmi H, alkyle C1-C4 éventuellement substitué par NR5R6; alcoxy C1-C4, halo, CONR5R6 et aryle; aryle représente phényle éventuellement substitué par un, deux ou trois substituants choisis indépendamment parmi alkyle C1-C4, alcoxy C1-C4, OH, halo et CF3; R5 et R6 sont choisis chacun indépendamment parmi H et alkyle C1-C4; et m et n valent chacun indépendamment 1, 2 ou 3. Ces composés sont des inhibiteurs puissants et sélectifs de la thrombine, utiles dans le traitement, entre autres, de la thrombose des veines profondes, de l'occlusion répétée après thérapie thrombolytique, de l'obstruction artérielle chronique, des maladies vasculaires périphériques, de l'infarctus du myocarde, de l'angor instable, de la fibrillation auriculaire, de l'accident vasculaire cérébral thrombotique, des attaques ischémiques passagères, de la resténose et de l'occlusion suivant une angioplastie, ou des troubles neurodégénératifs.
• Synthesis of 1,2,5,6-Tetrahydro-3-pyridinylalanine: A Key Intermediate in the Preparation of Thrombin Inhibitor UK-239,326
  作者：Paul V. Fish、Alan D. Brown、John C. Danilewicz、David Ellis、J. David Hardstone、Keith James

  DOI：10.1080/00397910701839210

  日期：2008.8.19

  A short synthesis of N-protected 1,2,5,6-tetrahydro-3-pyridinylalanine derivatives (8-10) was accomplished using a simple procedure of quaternization of (3-pyridyl)alanine 6 with benzyl bromide followed by reduction with NaBH(4). Amino acid 10 was then converted to thrombin inhibitor UK-239,326 (2), which required the sequential functionalization of four amines to give four different functional groups (viz., sulfonamide, carboxamide, guanidine, and methylamine).