(1S)-[3-chloro-1-(phenylmethyl)-2-hydroxypropyl]carbamic acid,1,1-dimethylethyl ester | 112739-73-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (1S)-[3-chloro-1-(phenylmethyl)-2-hydroxypropyl]carbamic acid,1,1-dimethylethyl ester
• 英文别名: [1(S)-benzyl-2(S)-hydroxy-3-chloropropyl]carbamic acid t-butyl ester；t-butyl [1(S)-benzyl-2(S)-hydroxy-3-chloropropyl]carbamate；3-tert-butoxycarbonylamino-1-chloro-2-hydroxy-4-phenylbutane；(2R,3S)-3-(Tert-butoxycarbonylamino)-1-chloro-2-hydroxy-4-phenylbutane；tert-butyl N-(4-chloro-3-hydroxy-1-phenylbutan-2-yl)carbamate
• CAS: 112739-73-8
• 化学式: C₁₅H₂₂ClNO₃
• 分子量: 299.798
• InChiKey: GFGQSTIUFXHAJS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  20
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  58.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (1S)-[3-chloro-1-(phenylmethyl)-2-hydroxypropyl]carbamic acid,1,1-dimethylethyl ester 以 四氢呋喃 、 乙酸乙酯 为溶剂， 生成 (S)-[1-(2,3-Epoxypropyl)phenylmethyl]carbamic acid, 1,1 dimethylethyl ester
  参考文献：
  名称：

  Aminocarbonyl renin inhibitors

  摘要：

  揭示了公式##STR1##的化合物。这些化合物通过抑制肾素干预将血管紧张素原转化为血管紧张素II，因此可用作降压药物。

  公开号：

  US04749781A1
• 作为产物：
  描述：

  (S)-[3-Chloro-2-oxo-1-(phenylmethyl)propyl]-carbamic acid,1,1-dimethylethyl ester 在 sodium borohydrid 作用下， 以 四氢呋喃 、 水 为溶剂， 生成 (1S)-[3-chloro-1-(phenylmethyl)-2-hydroxypropyl]carbamic acid,1,1-dimethylethyl ester
  参考文献：
  名称：

  Aminocarbonyl renin inhibitors

  摘要：

  揭示了公式##STR1##的化合物。这些化合物通过抑制肾素干预将血管紧张素原转化为血管紧张素II，因此可用作降压药物。

  公开号：

  US04749781A1

文献信息

• Process for producing alpha-aminoketones
  申请人：AJINOMOTO CO., INC.

  公开号：US20020035288A1

  公开（公告）日：2002-03-21

  A process for producing &agr;-aminohalomethyl ketones or N-protected &agr;-aminohalomethyl ketones from specified 3-oxazolidin-5-one derivatives via 5-halomethyl-5-hydroxy-3-oxazolidine derivatives. By this process, &agr;-aminohalomethyl ketones and compounds relating to them can be obtained efficiently and economically in industrial scale.

  从指定的3-噁唑烷-5-酮衍生物通过5-卤甲基-5-羟基-3-噁唑烷衍生物制备α-氨基卤甲基酮或N-保护的α-氨基卤甲基酮的过程。通过这个过程，可以在工业规模上高效经济地获得α-氨基卤甲基酮及相关化合物。
• Production method of beta-amino-alpha-hydroxycarboxylic acid
  申请人：AJINOMOTO CO. INC

  公开号：US20020151722A1

  公开（公告）日：2002-10-17

  The present invention provides a production method of an optically active &bgr;-amino-&agr;-hydroxycarboxylic acid, which includes the following steps (a)-(c): (a) treating an optically active N-carbamate protected &bgr;-amino epoxide with an acid to give an optically active 5-hydroxymethyl-2-oxazolidinone; (b) oxidizing the resulting compound in the presence of 2,2,6,6-tetramethyl-1-piperidinyloxy and hypochlorite to give an optically active 4-benzyl-2-oxo-5-oxazolidinecarboxylic acid; and (c) treating the 4-benzyl-2-oxo-5-oxazolidinecarboxylic acid with a base, and a production method of an optically active N-carbamate protected &bgr;-amino-&agr;-hydroxycarboxylic acid which includes protection of the amino group with a carbamate type protecting group. The industrial production method of the present invention can produce these compounds efficiently.

  本发明提供了一种光学活性β-氨基-α-羟基羧酸的生产方法，包括以下步骤(a)-(c)：(a) 用酸处理光学活性N-羰基保护的β-氨基环氧化合物，得到光学活性5-羟甲基-2-噁唑烷酮；(b) 在2,2,6,6-四甲基-1-哌啶氧和次氯酸盐存在下氧化所得化合物，得到光学活性4-苄基-2-氧代-5-噁唑烷羧酸；(c) 用碱处理4-苄基-2-氧代-5-噁唑烷羧酸，并且提供了一种光学活性N-羰基保护的β-氨基-α-羟基羧酸的生产方法，其中包括用羰酸酯型保护基保护氨基团。本发明的工业生产方法可以高效地生产这些化合物。
• 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。
• 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。
• PROCESS FOR REDUCING $G(a)-AMINO KETONES
  申请人：KANEKA CORPORATION

  公开号：EP0969000A1

  公开（公告）日：2000-01-05

  The present invention has its objects to provide a method for reducing α-aminoketone derivatives under mild conditions with high stereoselectivity. This invention is a method for reducing α-aminoketone which comprises reacting an α-aminoketone derivative of general formula (1) with a compound prepared from an organoaluminum compound of general formula (4), a sulfonic acid derivative of general formula (5), and an alcohol compound of general formula (6) to give an α-aminoalcohol derivative of general formula (7).

  本发明的目的是提供一种在温和条件下以高立体选择性还原α-氨基酮衍生物的方法。 本发明是一种还原α-氨基酮的方法，它包括将通式(1)的α-氨基酮衍生物与由通式(4)的有机铝化合物、通式(5)的磺酸衍生物和通式(6)的醇化合物制备的化合物反应，得到通式(7)的α-氨基醇衍生物。