(2S)-2-[(1S)-1-(4-bromo-phenyl)-2,2,2-trifluoro-ethylamino]-4-methyl-pentan-1-ol | 603142-80-9

• 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: (2S)-2-[(1S)-1-(4-bromo-phenyl)-2,2,2-trifluoro-ethylamino]-4-methyl-pentan-1-ol
• 英文别名: (1S,2S)-2-[1-(4-bromophenyl)-2,2,2-trifluoro-ethylamino]-4-methyl-pentan-1-ol；(2S)-2-{[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]amino}-4-methylpentan-1-ol；(S)-2-[[(S)-alpha-(Trifluoromethyl)-4-bromobenzyl]amino]-4-methyl-1-pentanol；(2S)-2-[[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]amino]-4-methylpentan-1-ol
• CAS: 603142-80-9
• 化学式: C₁₄H₁₉BrF₃NO
• 分子量: 354.21
• InChiKey: RWNYNOMOENCFPC-STQMWFEESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  32.3
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2S)-2-[(1S)-1-(4-bromo-phenyl)-2,2,2-trifluoro-ethylamino]-4-methyl-pentan-1-ol 在 palladium diacetate chromium(VI) oxide 、 sodium tungstate 、 双氧水 、 四丁基硫酸氢铵 、 sodium carbonate 、 高碘酸 、 三乙胺 、 三苯基膦 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 丙醇 、 水 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 为溶剂， 反应 9.5h， 生成 (2S)-4-methyl-2-[(1S)-2,2,2-trifluoro-1-(4'-methanesulfonyl-biphenyl-4-yl)ethylamino]-pentanoic acid cyanomethyl-amide
  参考文献：
  名称：

  Diastereoselective Arylithium Addition to an α-Trifluoromethyl Imine. Practical Synthesis of a Potent Cathepsin K Inhibitor

  摘要：

  A practical, chromatography-free synthesis of potent cathepsin K inhibitor 1 is described. The addition of 4-bromophenyllithium to an alpha-trifluoromethylimine derived from commercially available (S)-leucinol was accomplished in a highly diastereoselective manner (97.6% de, 91% yield). Subsequent Suzuki cross-coupling afforded biaryl 7. Oxidation of the alcohol and sulfide functionalities led to the formation of carboxylic acid 8. Crystallization of 7 and acid 8 as its dicyclohexylamine salt gave excellent impurity rejection. The final amide coupling with commercially available aminoacetonitrile hydrochloride afforded 1 in excellent purity (99.6A% by HPLC, 100% de, < 3 ppm Pd, W, Cr).

  DOI：

  10.1021/jo052430j
• 作为产物：
  描述：

  L-亮氨醇 在 三甲基氯硅烷 、 4-甲基苯磺酸吡啶 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 7.0h， 生成 (2S)-2-[(1S)-1-(4-bromo-phenyl)-2,2,2-trifluoro-ethylamino]-4-methyl-pentan-1-ol
  参考文献：
  名称：

  Oxazolidine Ring Opening and Isomerization to (E)-Imines. Asymmetric Synthesis of Aryl-α-fluoroalkyl Amino Alcohols

  摘要：

  A base-induced ring opening/imine isomerization/diastereoselective organometallic addition sequence on 4-substituted 2-perfluoroalkyl-1,3-oxazolidines has been developed for the asymmetric synthesis of aryl alpha-perfluoroalkylamine derivatives. This practical method provides chiral amino alcohols in 60-95% yield with uniformely high diastereoselectivities ranging from 35:1 to >100:1.

  DOI：

  10.1021/ol036486g

文献信息

• [EN] CATHEPSIN CYSTEINE PROTEASE INHIBITORS<br/>[FR] INHIBITEURS DE CATHEPSINE ET DE CYSTEINE PROTEASE
  申请人：MERCK FROSST CANADA INC

  公开号：WO2005019161A1

  公开（公告）日：2005-03-03

  This invention relates to a novel class of compounds, represented by the formula below, wherein the meanings of G, E, E, n, R1, R2, R3 et R4 are indicated therein, which are cysteine protease inhibitors, including but not limited to, inhibitors of cathepsins K, L, S and B. These compounds are useful for treating diseases in which inhibition of bone resorption is indicated, such as osteoporosis.

  本发明涉及一类新颖的化合物，其由下述公式表示，其中G、E、E、n、R1、R2、R3和R4的含义如公式中所示，这些化合物是半胱氨酸蛋白酶抑制剂，包括但不限于组织蛋白酶K、L、S和B的抑制剂。这些化合物可用于治疗那些指示抑制骨吸收的疾病，例如骨质疏松症。
• [EN] CATHEPSIN INHIBITORS<br/>[FR] INHIBITEURS DE LA CATHEPSINE
  申请人：MERCK FROSST CANADA INC

  公开号：WO2005021487A1

  公开（公告）日：2005-03-10

  This invention relates to a novel class of compounds, represented by the formula (I) below, wherein the meanings of R1, R2, R3 and R4 are indicated therein, which are cysteine protease inhibitors, including but not limited to, inhibitors of cathepsins K, L, S and B. These compounds are useful for treating diseases in which inhibition of bone resorption is indicated, such as osteoporosis, osteoarthritis and rheumatoid arthritis.

  这项发明涉及一类新型化合物，由下式（I）表示，其中R1、R2、R3和R4的含义已在其中指示，这些化合物是半胱氨酸蛋白酶抑制剂，包括但不限于对卡特普辛K、L、S和B的抑制剂。这些化合物对于治疗需要抑制骨吸收的疾病非常有用，如骨质疏松症、骨关节炎和类风湿性关节炎。
• Cathepsin cysteine protease inhibitors
  申请人：——

  公开号：US20030232863A1

  公开（公告）日：2003-12-18

  This invention relates to a novel class of compounds which are cysteine protease inhibitors, including but not limited to, inhibitors of cathepsins K, L, S and B. These compounds are useful for treating diseases in which inhibition of bone resorption is indicated, such as osteoporosis.

  这项发明涉及一类新型化合物，它们是半胱氨酸蛋白酶抑制剂，包括但不限于对卡特普辛K、L、S和B的抑制剂。这些化合物可用于治疗需要抑制骨吸收的疾病，如骨质疏松症。
• [EN] 4-AMINO-AZEPAN-3-ONE COMPOUNDS AS CATHEPSIN K INHIBITORS USEFUL IN THE TREATMENT OF OSTEOPOROSIS<br/>[FR] COMPOSES 4-AMINO-AZEPANE-3-ONE COMME INHIBITEURS DE LA CATHEPSINE K, UTILES DANS LE TRAITEMENT DE L'OSTEOPOROSE
  申请人：MERCK FROSST CANADA INC

  公开号：WO2004033445A1

  公开（公告）日：2004-04-22

  This invention relates to compounds of formula (I) which are cysteine protease inhibitors, in particular, inhibitors of cathepsins K, L, S and B. These compounds are useful for treating diseases in which inhibition of bone resorption is indicated, such as osteoporosis.

  这项发明涉及化合物的公式(I)，这些化合物是半胱氨酸蛋白酶抑制剂，特别是对卡特普辛K、L、S和B的抑制剂。这些化合物可用于治疗需要抑制骨吸收的疾病，如骨质疏松症。
• Cathepsin inhibitors
  申请人：Bayly Christopher

  公开号：US20060287402A1

  公开（公告）日：2006-12-21

  This invention relates to a novel class of compounds, represented by the formula (I) below, wherein the meanings of R 1 , R 2 , R 3 and R 4 are indicated therein, which are cysteine protease inhibitors, including but not limited to, inhibitors of cathepsins K, L, S and B. These compounds are useful for treating diseases in which inhibition of bone resorption is indicated, such as osteoporosis, osteoarthritis and rheumatoid arthritis.

  本发明涉及一类新型化合物，其公式表示为(I)，其中R1、R2、R3和R4的含义如下所示，它们是半胱氨酸蛋白酶抑制剂，包括但不限于对卡特普西林K、L、S和B的抑制剂。这些化合物可用于治疗需要抑制骨吸收的疾病，例如骨质疏松症、骨关节炎和类风湿性关节炎。