Synthesis of sibutramine, a novel cyclobutylalkylamine useful in the treatment of obesity, and its major human metabolites

被引：26

作者：

Jeffery, JE ^{[1
]}

Kerrigan, F ^{[1
]}

Miller, TK ^{[1
]}

Smith, GJ ^{[1
]}

Tometzki, GB ^{[1
]}

机构：

[1] KNOLL PHARMACEUT, DEPT RES & DEV, NOTTINGHAM NG1 1GF, ENGLAND

来源：

JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1 | 1996年 / 21期

关键词：

D O I：

10.1039/p19960002583

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

Synthetic routes to N-{1-[1-(4-chlorophenyl)cyclobutyl]-3-methylbutyl}-N, N-dimethylamine(sibutramine) I and its demethylated and hydroxylated human metabolites N-{1-[1-(4-chlorophenyl)cyclobutyl]-3-methylbutyl}-N-methylamine 2, 1-[1-(4-chlorophenyl)cyclobutyl]-3-methylbutylamine 3, 4-amino-4-[1-(4-chlorophenyl)cyclobutyl]-2-methylbutan-1-ol 4 and c-3-(1-amino-3-methylbutyl)-3-(4-chlorophenyl)cyclobutan-r-1-ol 5a are described, Key steps are tandem Grignard-reduction reactions on 1-(4-chlorophenyl)cyclobutanecarbonitrile 7 and its 3-(tetrahydropyran-2-yloxy)substituted analogue 14 and a convenient one-pot conversion of 4-chlorophenylacetonitrile 6 into the 3-hydroxycyclobutanecarbonitrile 13.

引用

页码：2583 / 2589

页数：7

共 28 条

[1] HEALTH IMPLICATIONS OF OBESITY - NATIONAL-INSTITUTES-OF-HEALTH CONSENSUS DEVELOPMENT CONFERENCE STATEMENT [J].

不详 .

ANNALS OF INTERNAL MEDICINE, 1985, 103 (06) :1073-1077

[2]

BOGATSKII AV, 1974, VOPR STEREOKHIM, V4, P49

[3]

Bray G. A., 1994, International Journal of Obesity, V18, P60

[4]

BRAY GA, 1991, PROG OBES R, P639

[5] THE PHARMACOLOGY OF SIBUTRAMINE HYDROCHLORIDE (BTS54524), A NEW ANTIDEPRESSANT WHICH INDUCES RAPID NORADRENERGIC DOWN-REGULATION [J].

BUCKETT, WR ;

THOMAS, PC ;

LUSCOMBE, GP .

PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY, 1988, 12 (05) :575-584

[6] FACILE CYCLOALKYLATION OF ARYLACETONITRILES IN DIMETHYL SULFOXIDE [J].

BUTLER, DE ;

POLLATZ, JC .

JOURNAL OF ORGANIC CHEMISTRY, 1971, 36 (09) :1308-&

[7]

CAHIEZ G, 1978, TETRAHEDRON LETT, P3013

[8]

Clarke H.T., 1933, J AM CHEM SOC, V55, P4571, DOI [10.1021/ja01338a041, DOI 10.1021/JA01338A041]

[9] CONTROL OF RING SIZE RESULTING FROM GAMMA-EPOXY SULFONE AND GAMMA-EPOXYNITRILE CYCLIZATION - FORMATION OF EITHER CYCLOPROPYL OR CYCLOBUTYL DERIVATIVES [J].

CORBEL, B ;

DURST, T .

JOURNAL OF ORGANIC CHEMISTRY, 1976, 41 (22) :3648-3650

[10]

COURTOIS G, 1983, B SOC CHIM FR II-CH, P21

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