(3R)-3-(N-叔丁氧羰基氨基)-1-氯-4-苯基-2-丁酮 | 150935-37-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: (3R)-3-(N-叔丁氧羰基氨基)-1-氯-4-苯基-2-丁酮
• 中文别名: Boc-D-苯丙氨酸氯甲基酮；(3R)-3-(n-boc-氨基)-1-氯-4-苯基-2-丁酮
• 英文名称: (R)-(1-benzyl-3-chloro-2-oxopropyl)carbamic acid t-butyl ester
• 英文别名: (R)-tert-butyl 4-chloro-3-oxo-1-phenylbutan-2-ylcarbamate；(3R)-3-tert-butoxycarbonylamino-1-chloro-4-phenyl-2-butanone；t-butyl (R)-(1-benzyl-3-chloro-2-oxopropyl)carbamate；(R)-1-benzyl-3-chloro-2-oxopropylcarbamic acid tert-butyl ester；(R)-3-(tert-Butoxycarbonylamino)-1-chloro-4-phenylbutan-2-one；(3R)-3-(N-Boc-amino)-1-chloro-4-phenyl-2-butanone；tert-butyl N-[(2R)-4-chloro-3-oxo-1-phenylbutan-2-yl]carbamate
• CAS: 150935-37-8
• 化学式: C₁₅H₂₀ClNO₃
• 分子量: 297.782
• InChiKey: JAKDNFBATYIEIE-GFCCVEGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  20
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2924299090

反应信息

• 作为反应物：
  描述：

  (3R)-3-(N-叔丁氧羰基氨基)-1-氯-4-苯基-2-丁酮 在 aluminum isopropoxide 、 三乙胺 、 异丙醇 、 sodium hydroxide 作用下， 以 二氯甲烷 、 丙酮 为溶剂， 反应 9.5h， 生成 N-[(1R,2S)-2-羟基-3-[(2-甲基丙基)[(4-硝基苯基)磺酰基]氨基]-1-(苯基甲基)丙基]氨基甲酸叔丁酯
  参考文献：
  名称：

  Babu, Kilaru Ravendra; Rao, Valasani Koteswara; Sudhakar, Yellapu, Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2012, vol. 51, # 6, p. 849 - 854

  摘要：

  DOI：
• 作为产物：
  描述：

  D-苯丙氨酸甲酯 在 甲基氯化镁 、 碳酸氢钠 作用下， 以 四氢呋喃 为溶剂， 反应 19.25h， 生成 (3R)-3-(N-叔丁氧羰基氨基)-1-氯-4-苯基-2-丁酮
  参考文献：
  名称：

  Babu, Kilaru Ravendra; Rao, Valasani Koteswara; Sudhakar, Yellapu, Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2012, vol. 51, # 6, p. 849 - 854

  摘要：

  DOI：

文献信息

• Method for producing epoxide crystal
  申请人：Ajinomoto Co., Inc.

  公开号：US20020072621A1

  公开（公告）日：2002-06-13

  The invention relates to a method for industrially producing highly pure (2R, 3S)- or (2S, 3R)-N-carbamate-protected &bgr;-aminoepoxide (crystal) or (2R, 3S)- or (2S, 3R)-N-carbamate-protected &bgr;-aminoalcohol. The method for producing N-carbamate-protected &bgr;-aminoepoxide crystal, includes one or more of the following steps (a) to (d): (a) dissolving (2R, 3S)- or (2S, 3R)-N-carbamate-protected &bgr;-aminoalcohol containing at least the diastereomer as an impurity in a solvent including at least one or more selected from aromatic hydrocarbon solvent, saturated hydrocarbon solvent, aqueous mixture solvent, acetone and 2-propanol, to remove insoluble matters; (b) treating the (2R, 3S)- or (2S, 3R)-N-carbamate-protected &bgr;-aminoalcohol with a base, thereby converting the N-carbamate-protected &bgr;-aminoalcohol to (2R, 3S)- or (2S, 3R)-N-carbamate-protected &bgr;-aminoepoxide; (c) treating the (2R, 3S)- or (2S, 3R)-N-carbamate-protected &bgr;-aminoepoxide containing at least the diastereomer as an impurity with an acid, thereby converting the diastereomer as an impurity to (4S, 5R) or (4R, 5S) oxazolidin-2-one derivative, and optionally separating and removing the resulting oxazolidin-2-one derivative in water or an aqueous mixture solvent; and (d) crystallizing the (2R, 3S)- or (2S, 3R)-N-carbamate-protected &bgr;-aminoepoxide in a mixture solvent of water and water-miscible organic solvent. By the methods of the present invention, highly pure (2R, 3S)- or (2S, 3R)-N-carbamate-protected &bgr;-aminoepoxide or (2R, 3S) or (2S, 3R)-N-carbamate-protected &bgr;-aminoalcohol can be efficiently produced.

  该发明涉及一种工业生产高纯度(2R, 3S)或(2S, 3R)-N-碳酸酯保护的β-氨基环氧乙烷(晶体)或(2R, 3S)或(2S, 3R)-N-碳酸酯保护的β-氨基醇的方法。生产N-碳酸酯保护的β-氨基环氧乙烷晶体的方法包括以下一项或多项步骤(a)至(d)：(a)将至少含有对映异构体作为杂质的(2R, 3S)或(2S, 3R)-N-碳酸酯保护的β-氨基醇溶解于包括至少选择自芳香烃溶剂、饱和烃溶剂、水混合溶剂、丙酮和异丙醇的溶剂中，以去除不溶物质；(b)用碱处理(2R, 3S)或(2S, 3R)-N-碳酸酯保护的β-氨基醇，从而将N-碳酸酯保护的β-氨基醇转化为(2R, 3S)或(2S, 3R)-N-碳酸酯保护的β-氨基环氧乙烷；(c)用酸处理至少含有对映异构体作为杂质的(2R, 3S)或(2S, 3R)-N-碳酸酯保护的β-氨基环氧乙烷，从而将对映异构体作为杂质转化为(4S, 5R)或(4R, 5S)噁唑烷-2-酮衍生物，并可在水或水混合溶剂中分离和去除所得的噁唑烷-2-酮衍生物；(d)在水和水亲和性有机溶剂的混合溶剂中结晶(2R, 3S)或(2S, 3R)-N-碳酸酯保护的β-氨基环氧乙烷。通过本发明的方法，可以高效生产高纯度的(2R, 3S)或(2S, 3R)-N-碳酸酯保护的β-氨基环氧乙烷或(2R, 3S)或(2S, 3R)-N-碳酸酯保护的β-氨基醇。
• Melanocortin receptor ligands
  申请人：Ebetino Hallock Frank

  公开号：US20060128613A1

  公开（公告）日：2006-06-15

  Disclosed are MC-4 and/or MC-3 receptor ligands, the ligands having a structure according to Formula (I): wherein R 2 , R 4 , R 4′ , R 5 , R 6 , R 6′ , R 7 , R 8 , R 8′ , R 9 , R 9′ , R 10 , Ar, Z 1 , Z 2 , Z 3 , X, B, D, p, q, r and s are as described in the specification and claims, and optical isomers, diastereomers or enantiomers thereof; pharmaceutically-acceptable salts, hydrates, and biohydrolyzable esters, amides or imides thereof. Also disclosed are pharmaceutical compositions comprising the ligands of Formula (I), as well as methods of treating diseases mediate by the MC-4/MC-3 receptors, as described in the Detailed Descriptions section of the specification.

  公开了MC-4和/或MC-3受体配体，该配体具有按照式（I）的结构：其中R2、R4、R4'、R5、R6、R6'、R7、R8、R8'、R9、R9'、R10、Ar、Z1、Z2、Z3、X、B、D、p、q、r和s如说明书和索赔中所述，以及其光学异构体、二对映异构体或对映体；药用盐、水合物和生物水解酯、酰胺或亚酰胺。还公开了包括式（I）配体的药物组合物，以及治疗由MC-4/MC-3受体介导的疾病的方法，如说明书的详细描述部分所述。
• 1-Amino Linked Compounds
  申请人：Blaszczak Larry Chris

  公开号：US20080207735A1

  公开（公告）日：2008-08-28

  The present invention is directed to compounds of formula (I): or a pharmaceutically acceptable salt thereof; wherein A is (II); X is selected from CH, CF and N, R8 is selected from H, C 1 -C 6 alkyl, aryl, heteroaryl, C 1 -C 6 alkylaryl, C 1 -C 6 alkylheteroaryl, C 2 -C 6 alkyl-O—C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, hydroxy C 2 -C 6 alkyl, —C(O)R9 and —SO 2 R9, or R7 and R8 combine to form (III), (IV); W is selected from CR1O and CR15, R1O is selected from H, halo, —C(O)NR13R14, C 1 -C 6 alkyl, aryl, heteroaryl, C 1 -C 6 alkylaryl, C 1 -C 6 alkylheteroaryl, C 1 -C 6 alkyl-O—C 1 -C 6 alkyl and hydroxy C 1 -C 6 alkyl; Het is a N-linked 5-membered heteroaryl ring optionally substituted with 1-3 substituents selected from methoxy, Cl, F, CH 3 , CF 3 , aryl, heteroaryl, C 1 -C 4 alkylaryl or C 1 -C 4 alkylheteroaryl, for use as inhibitors of the DPP-IV enzyme in the treatment or prevention of conditions including Type II diabetes.

  本发明涉及以下式(I)的化合物或其药学上可接受的盐;其中A为(II);X选自CH、CF和N，R8选自H、C1-C6烷基、芳基、杂环芳基、C1-C6烷基芳基、C1-C6烷基杂环芳基、C2-C6烷基-O-C1-C6烷基、C1-C6卤代烷基、羟基C2-C6烷基、-C（O）R9和-SO2R9，或R7和R8结合形成(III)、(IV);W选自CR1O和CR15，R1O选自H、卤、-C（O）NR13R14、C1-C6烷基、芳基、杂环芳基、C1-C6烷基芳基、C1-C6烷基杂环芳基、C1-C6烷基-O-C1-C6烷基和羟基C1-C6烷基;Het是一种N-连接的5-成员杂环芳基环，可选地被1-3个取代基所取代，所述取代基选自甲氧基、Cl、F、CH3、CF3、芳基、杂环芳基、C1-C4烷基芳基或C1-C4烷基杂环芳基，用作DPP-IV酶的抑制剂，治疗或预防包括II型糖尿病在内的疾病。
• 1-amino linked compounds
  申请人：Eli Lilly and Company

  公开号：US08106090B2

  公开（公告）日：2012-01-31

  The present invention is directed to compounds of formula (I): or a pharmaceutically acceptable salt thereof; wherein A is (II); X is selected from CH, CF and N, R8 is selected from H, C1-C6 alkyl, aryl, heteroaryl, C1-C6 alkylaryl, C1-C6 alkylheteroaryl, C2-C6 alkyl-O—C1-C6 alkyl, C1-C6 haloalkyl, hydroxy C2-C6 alkyl, —C(O)R9 and —SO2R9, or R7 and R8 combine to form (III), (IV); W is selected from CR1O and CR15, R1O is selected from H, halo, —C(O)NR13R14, C1-C6 alkyl, aryl, heteroaryl, C1-C6 alkylaryl, C1-C6 alkylheteroaryl, C1-C6 alkyl-O—C1-C6 alkyl and hydroxy C1-C6 alkyl; Het is a N-linked 5-membered heteroaryl ring optionally substituted with 1-3 substituents selected from methoxy, Cl, F, CH3, CF3, aryl, heteroaryl, C1-C4 alkylaryl or C1-C4 alkylheteroaryl, for use as inhibitors of the DPP-IV enzyme in the treatment or prevention of conditions including Type II diabetes.

  本发明涉及式(I)的化合物或其药学上可接受的盐；其中A为(II)；X选自CH、CF和N，R8选自H、C1-C6烷基、芳基、杂环芳基、C1-C6烷基芳基、C1-C6烷基杂环芳基、C2-C6烷基-O-C1-C6烷基、C1-C6卤代烷基、羟基C2-C6烷基、-C(O)R9和-SO2R9，或R7和R8结合形成(III)、(IV)；W选自CR1O和CR15，R1O选自H、卤素、-C(O)NR13R14、C1-C6烷基、芳基、杂环芳基、C1-C6烷基芳基、C1-C6烷基杂环芳基、C1-C6烷基-O-C1-C6烷基和羟基C1-C6烷基；Het是一种N-连接的5-成员杂环芳基环，可选地被1-3个取代基所取代，所述取代基选自甲氧基、Cl、F、CH3、CF3、芳基、杂环芳基、C1-C4烷基芳基或C1-C4烷基杂环芳基，用作DPP-IV酶抑制剂，用于治疗或预防包括II型糖尿病在内的疾病。
• KETOREDUCTASE-MEDIATED STEREOSELECTIVE ROUTE TO ALPHA CHLOROALCOHOLS
  申请人：Bong Yong Koy

  公开号：US20120190086A1

  公开（公告）日：2012-07-26

  The present disclosure relates to engineered ketoreductase polypeptides and uses thereof for the preparation of α chloroalcohols from α chloroketones. Also provided are polynucleotides encoding the engineered ketoreductase polypeptides and host cells capable of expressing the engineered ketoreductase polypeptides.

  本公开涉及工程化的酮还原酶多肽及其在制备α-氯代醇中的应用。还提供了编码工程酮还原酶多肽的多核苷酸和能够表达工程酮还原酶多肽的宿主细胞。