2(R,S)-Methyl-β-alanine tert-butyl ester | 120786-19-8

• 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: 2(R,S)-Methyl-β-alanine tert-butyl ester
• 英文别名: t-butyl-3-amino-2-methylpropionate；tert-butyl 3-amino-2-methylpropanoate；2-tert-butoxycarbonyl-1-propylamine
• CAS: 120786-19-8
• 化学式: C₈H₁₇NO₂
• 分子量: 159.228
• InChiKey: ZCDAFFAFDGDAGL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  11
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  52.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2(R,S)-Methyl-β-alanine tert-butyl ester 在 sodium hydroxide 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 乙醇 、 氯仿 、 水 为溶剂， 反应 7.0h， 生成 (E)-3-(2-tert-Butoxycarbonyl-propylcarbamoyl)-4-phenyl-but-3-enoic acid
  参考文献：
  名称：

  New kelatorphan-related inhibitors of enkephalin metabolism: improved antinociceptive properties

  摘要：

  In order to improve the in vivo protection of enkephalins from enzymatic degradation, a new series of inhibitors derived from kelatorphan [HONHCOCH2CH(CH2Ph)CONHCH(CH3)COOH], the first-described complete inhibitor of enkephalin metabolism, were designed by modification of the C-terminal amino acid. The progressive lengthening of the chain of this residue shows that a beta-alanine seems to be the best basic model for the conception of such types of compounds. On the other hand, the methylation of the amide bond, which is well accepted by aminopeptidase N (EC 3.4.11.2) and dipeptidylaminopeptidase, induced a significant loss of affinity for neutral endopeptidase -24.11. Starting from these data, compounds containing a variously substituted beta-alanine residue and corresponding to the general formula HONHCOCH2CH(CH2Ph)CONHCH(R1)CH(R2)COOH were synthesized. All these molecules inhibit neutral endopeptidase -24.11 and dipeptidylaminopeptidase in the nanomolar range, and those containing an aromatic chain (compound 7A, R1 = CH2Ph,R2 = H, and compound 8A, R1 = Ph, R2 = H) inhibit the biologically relevant aminopeptidase N, with IC50's around 10(-8) M. Intracerebroventricular injection in mice of these multienzyme inhibitors produced an efficient and naloxone-reversible analgesic response (hot plate test): compounds 7A and 8A were shown to be more potent than kelatorphan in increasing the jump latency time, in agreement with their in vitro properties, and these new compounds were found to increase the forepaw lick latency, a reflex considered as a typical morphine response.

  DOI：

  10.1021/jm00127a017
• 作为产物：
  描述：

  甲基丙烯酸叔丁酯 在 20% palladium hydroxide-activated charcoal 、 氢气 、 溶剂黄146 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 甲醇 、 水 为溶剂， 反应 31.0h， 生成 2(R,S)-Methyl-β-alanine tert-butyl ester
  参考文献：
  名称：

  Controlling Intramolecular Interactions in the Design of Selective, High-Affinity Ligands for the CREBBP Bromodomain

  摘要：

  DOI：

  10.1021/acs.jmedchem.1c00348

文献信息

• A Versatile Reagent and Method for Direct Aliphatic Sulfonylation
  作者：Andre Shavnya、Kevin D. Hesp、Andy S. Tsai

  DOI：10.1002/adsc.201800071

  日期：2018.5.2

  methodology has been developed for the two‐step synthesis of aliphatic sulfinate salts, sulfonamides, sulfonyl fluorides, and unsymmetrical sulfones on the basis of alkylation of a new versatile sulfonylating reagent. The new reagent is easily accessible in one step; the developed protocols are conducted under mild conditions and have a broad substrate scope.

  在新型通用磺酰化试剂的烷基化基础上，开发了一种有效的方法，用于脂族亚磺酸盐，磺酰胺，磺酰氟和不对称砜的两步合成。只需一步即可轻松获得新试剂。所开发的方案是在温和的条件下进行的，具有广泛的底物范围。
• Reaction of Alkyl Halides with Rongalite: One-Pot and Telescoped Syntheses of Aliphatic Sulfonamides, Sulfonyl Fluorides, and Unsymmetrical Sulfones
  作者：Andre Shavnya、Steven B. Coffey、Kevin D. Hesp、Stuart C. Ross、Andy S. Tsai

  DOI：10.1021/acs.orglett.6b02894

  日期：2016.11.18

  An efficient methodology has been developed for the one-pot or telescoped synthesis of aliphatic sulfonamides, sulfonyl fluorides, and unsymmetrical sulfones on the basis of interrupted alkylation of sodium hydroxymethylsulfinate (rongalite) with alkyl halides. The protocols are conducted under mild conditions, use inexpensive and shelf-stable reagents, and are not sensitive to air/moisture. These

  已经开发了一种有效的方法，用于在羟甲基亚磺酸钠（荣格石）与烷基卤的间断烷基化的基础上，单锅或望远镜式合成脂族磺酰胺，磺酰氟和不对称砜。该方案是在温和的条件下进行的，使用廉价且耐贮存的试剂，并且对空气/水分不敏感。这些条件可用于快速平行化学合成，这是通过基于抗凝血药替罗非班的核心结构制备小的磺酰胺库证明的。
• Cycloalkyl-substituted glutaramide diuretic agents
  申请人：Pfizer Limited

  公开号：EP0343911A2

  公开（公告）日：1989-11-29

  Compounds having the formula: wherein A completes a 4 to 7 membered carbocyclic ring which may be saturated or mono-unsaturated and which may optionally be fused to a further carbocyclic ring; B is (CH2)m wherein m is 1 to 3; R and R4 are H, C1-C6 alkyl, benzyl or biolabile ester-forming groups; R1 is H or C1-C4 alkyl; R2 and R3 are each H, OH, C1-C6 alkyl or C1-C6 alkoxy, or are linked together and are (CH2)r wherein r is 1 to 4; Y is an optional alkylene group of from 1 to 6 carbon atoms which may be straight or branched-chain; and R5 is R6CONR9-, R6SO2NR9-, R6CO2-, R6CO-, R6SOq-, R7NR9CO-, R7NR9S02- or R70CO-; wherein R6 is a group of the formula R8(R1OR11C-CONR9)nR1OR11C-; R7 is a group of the formula R10R11R12C- and R9 is H, C1-C6 alkyl, aryl, C3-C7 cycloalkyl, heterocyclyl, aryl(C1-C6 alkyl) or heterocyclyl(C1-C6 alkyl); wherein R8 is R9CONR9-, R9SO2NR9-, R13R14-N-(CH2)p-, or R90-, R10 and R11 are H or C1-C6 alkyl; or R10 is H and R11 is C1-C6 alkyl which is substituted by OH, SH, SCH3, NH2, aryl(C1-C6 alkyl)OCONH-, NH2CO-, C02H, guanidino, aryl, or heterocyclyl; or the two groups R10 and R11 are joined to form a five or 6 membered carbocyclic ring which may be saturated, mono-unsaturated, optionally substituted by C1-C4 alkyl or fused to a further carbocylic ring; or R8 and R11 are linked to form a 2-(N-COR9-4-aminopyrrolidinyl) group; R12 is R13R14NCO-, R90CO-, R90CH2- or heterocyclyl, R13 and R14 are H, C1-C6 alkyl, C3-C7 cycloalkyl, aryl, aryl(C1-C6 alkyl), C2-Cs alkoxyalkyl, amino (C1-C6 alkyl), heterocyclyl or heterocyclyl(C1-C6alkyl); or the two groups R13 and R14 form a pyrrolidinyl, piperidino, morpholino, piperazinyl, N-(C1-C4 alkyl) piperazinyl, pyrrolyl, imidazolyl, pyrazolyl or triazolyl group; n is 0 or 1; p is 0 or 1 to 6; and q is 0, 1 or 2; and pharmaceutically acceptable salts thereof and bioprecursors therefor, are diuretic agents of value in the treatment of hypertension, heart failure and renal insufficiency.

  具有以下式子的化合物 其中 A 是一个 4 至 7 个成员的碳环，可以是饱和的或单不饱和的，并可选 择与另一个碳环融合；B 是 (CH2)m，其中 m 是 1 至 3；R 和 R4 是 H、C1-C6 烷基、苄基或可形成生物酯的基团；R1 是 H 或 C1-C4 烷基；R2 和 R3 各自是 H、OH、C1-C6 烷基或 C1-C6 烷氧基，或连接在一起且是 (CH2)r，其中 r 是 1 至 4；Y 是 1 至 6 个碳原子的任选亚烷基，可以是直链或支链； 和 R5 是 R6CONR9-、R6SO2NR9-、R6CO2-、R6CO-、R6SOq-、R7NR9CO-、R7NR9S02- 或 R70CO-； 其中 R6 是式 R8(R1OR11C-CONR9)nR1OR11C-的基团；其中 R7 是式 R10R11R12C- 的基团，R9 是 H、C1-C6 烷基、芳基、C3-C7 环烷基、杂环烷基、芳基（C1-C6 烷基）或杂环烷基（C1-C6 烷基）； 其中 R8 是 R9CONR9-、R9SO2NR9-、R13R14-N-(CH2)p- 或 R90-，R10 和 R11 是 H 或 C1-C6 烷基；或 R10 是 H，R11 是被 OH、SH、SCH3、NH2、芳基（C1-C6 烷基）OCONH-、NH2CO-、C02H、胍基、芳基或杂环取代的 C1-C6 烷基；或两个基团 R10 和 R11 连接形成一个五或六位碳环，该碳环可以是饱和的、单不饱和的、任选被 C1-C4 烷基取代的或与另一个碳环融合的；或 R8 和 R11 连接形成一个 2-(N-COR9-4-氨基吡咯烷基)基团；R12 是 R13R14NCO-、R90CO-、R90CH2- 或杂环烷基，R13 和 R14 是 H、C1-C6 烷基、C3-C7 环烷基、芳基、芳基（C1-C6 烷基）、C2-Cs 烷氧基烷基、氨基（C1-C6 烷基）、杂环烷基或杂环烷基（C1-C6 烷基）；或两个基团 R13 和 R14 形成吡咯烷基、哌啶基、吗啉基、哌嗪基、N-（C1-C4 烷基）哌嗪基、吡咯基、咪唑基、吡唑基或三唑基；n 为 0 或 1；p 为 0 或 1 至 6；和 q 是 0、1 或 2；及其药学上可接受的盐和生物前体，是治疗高血压、心力衰竭和肾功能不全的有价值的利尿剂。
• AGENT FOR TREATMENT OR PREVENTION OF DISEASES ASSOCIATED WITH ACTIVITY OF NEUROTROPHIC FACTORS
  申请人：Sumitomo Chemical Company, Limited

  公开号：EP2436683B1

  公开（公告）日：2014-05-14
• XIE, JUAN;SOLEILHAC, JEAN-MARC;SCHMIDT, CATHERINE;PEYROUX, JACQUES;ROQUES+, J. MED. CHEM., 32,(1989) N, C. 1497-1503
  作者：XIE, JUAN、SOLEILHAC, JEAN-MARC、SCHMIDT, CATHERINE、PEYROUX, JACQUES、ROQUES+

  DOI：——

  日期：——