An Efficient and Scalable Synthesis of (2R,αS)-3,4-Dihydro-2-[3-(1, 1,2,2-tetrafluoroethoxy)phenyl]-5-[3-(trifluoromethoxy)-phenyl]-α-(trifluoromethyl)-1(2H)-quinolineethanol: A Potent CETP Inhibitor

被引：0

作者：

Wang, Aihua ^{[1
]}

Zhang, Yan ^{[1
]}

Lu, Songfeng ^{[1
]}

Murray, William V. ^{[1
]}

Kuo, Gee-Hong ^{[1
]}

机构：

[1] Johnson & Johnson Pharmaceut Res & Dev LLC, Drug Discovery, Spring House, PA 19477 USA

来源：

JOURNAL OF HETEROCYCLIC CHEMISTRY | 2010年 / 47卷 / 06期

关键词：

LIPID TRANSFER PROTEINS; CORONARY-HEART-DISEASE; LIPOPROTEIN CHOLESTEROL; DISCOVERY; REDUCTION; DESIGN;

D O I：

10.1002/jhet.488

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

An efficient and scalable synthesis of the potent CETP inhibitor, (2R,alpha S)-3,4-dihydro-2[3-(,1,2,2-tetrafluoroethoxy)phenyl]-5-[3-(trifluoromethoxy)phenyl]-alpha-(trifluoromethyl)-1(2H)-quinolineethanol 1, is described. One of the important intermediates, tetrahydroquinoline 10, was readily prepared by reductive cyclization of nitroketone 9 in high yield. Asymmetric synthesis of 10 with high enantiomeric excess (>80% ee) was also developed.

引用

页码：1406 / 1410

页数：5

共 25 条

[1] High-density lipoprotein cholesterol as a predictor of coronary heart disease risk. The PROCAM experience and pathophysiological implications for reverse cholesterol transport [J].

Assmann, G ;

Schulte, H ;

vonEckardstein, A ;

Huang, YD .

ATHEROSCLEROSIS, 1996, 124 :S11-S20

[2] Atheroprotective effects of high-density lipoproteins [J].

Assmann, G ;

Nofer, JR .

ANNUAL REVIEW OF MEDICINE, 2003, 54 :321-341

[3] ASYMMETRIC REDUCTION OF 7,8-DIFLUORO-3-METHYL-2H-1,4-BENZOXAZINE - SYNTHESIS OF A KEY INTERMEDIATE OF (S)-(-)-OFLOXACIN (DR-3355) [J].

ATARASHI, S ;

TSURUMI, H ;

FUJIWARA, T ;

HAYAKAWA, I .

JOURNAL OF HETEROCYCLIC CHEMISTRY, 1991, 28 (02) :329-331

[4] Synthesis and antibacterial activity of some 5-(4-biphenylyl)-7-aryl[3,4-d] [1,2,3]-benzothiadiazoles [J].

Balasankar, T ;

Gopalakrishnan, M ;

Nagarajan, S .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2005, 40 (07) :728-731

[5] SELECTIVE REDUCTION OF AROMATIC NITRO-COMPOUNDS WITH STANNOUS CHLORIDE IN NON-ACIDIC AND NON-AQUEOUS MEDIUM [J].

BELLAMY, FD ;

OU, K .

TETRAHEDRON LETTERS, 1984, 25 (08) :839-842

[6] Plasma lipid transfer proteins, high-density lipoproteins, and reverse cholesterol transport [J].

Bruce, C ;

Chouinard, RA ;

Tall, AR .

ANNUAL REVIEW OF NUTRITION, 1998, 18 :297-330

[7] INCIDENCE OF CORONARY HEART-DISEASE AND LIPOPROTEIN CHOLESTEROL LEVELS - THE FRAMINGHAM-STUDY [J].

CASTELLI, WP ;

GARRISON, RJ ;

WILSON, PWF ;

ABBOTT, RD ;

KALOUSDIAN, S ;

KANNEL, WB .

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1986, 256 (20) :2835-2838

[8]

Corey EJ, 1998, ANGEW CHEM INT EDIT, V37, P1987, DOI 10.1002/(SICI)1521-3773(19980817)37:15<1986::AID-ANIE1986>3.0.CO

[9]

2-Z

[10] RANGE OF SERUM-CHOLESTEROL VALUES IN THE POPULATION DEVELOPING CORONARY-ARTERY DISEASE [J].

KANNEL, WB .

AMERICAN JOURNAL OF CARDIOLOGY, 1995, 76 (09) :C69-C77

← 1 2 3 →