西力士 [CAS171596-29-5]合成路线图解-原料药厂家东康源.docVIP

西力士 [CAS:171596-29-5]合成路线图解 核心提示：NameTadalafil;GF-196960;IC-351;Cialis Chemical Name 6R,12aR -6- 1,3-Benzodioxol-5-yl -2-methyl-1,2,3,4,6,7,12,12a-octah Chemical Name 6R,12aR -6- 1,3-Benzodioxol-5-yl -2-methyl-1,2,3,4,6,7,12,12a-octahydropyrazino[1,2:1,6]pyrido [3,4-b]indole-1,4-dione CAS 171596-29-5 Related CAS 240822-07-5, 171488-03-2 trans-isomer Formula C22H19N3O4 Structure Formula Weight 389.41443 Tel E-mail Mr Yuan 座机电话号码 1座机电话号码89 chem@ Company GlaxoSmithKline Originator , Lilly Icos Marketer , Lilly Licensee , Lilly Icos Licensee Activity/Mechanism Disorders of Sexual Function and Reproduction, Treatment of, ENDOCRINE DRUGS, RENAL-UROLOGIC DRUGS, Treatment of Diabetic Complications, Treatment of Erectile Dysfunction, Treatment of Female Sexual Dysfunction, Treatment of Male Sexual Dysfunction, Phosphodiesterase V PDE5A Inhibitors Syn. Route 1 Route 1 cyclization of d-tryptophan methyl ester i with piperonal ii by means of tfa in dichloromethane gives, after separation of the undesired trans-isomer by flash chromatography, the 1r,3r-cis -pyrido-indole derivative iii . the acylation of iii with chloroacetyl chloride iv and nahco3 in chloroform yields the chloroacetyl derivative v , which is finally cyclized with methylamine in methanol. List of intermediates No. 1r,4r -4-[[tert-butyl dimethyl silyl]oxy]-2-cyclopenten-1-ol ii 1- methylamino -3-tetracyclo[ 2,7 .0 9,14 ]hexadeca-2,4,6,9,11,13-hexaen-1-yl-2-propanol iv 1- 3-chlorophenyl -2- dimethylamino -1-ethanone i 5,6-dihydrobenzo[h]cinnolin-3-ylamine; 5,6-dihydrobenzo[h]cinnolin-3-amine iii ethyl omega-bromoundecanoate; ethyl 11-bromoundecanoate v Reference 1: daugan, a.; grondin, p.; ruault, c.; et al.; the discovery of tadalafil: a novel and highly selective pde5 inhibitor. 2: 2,3,6,7,12,12a-hexahydropyrazino[1,2:1,6]pyrido[3,4-b]indole-1,4-dione analogues. j med chem 2003, 46, 21, 4533. Reference 2: martin, l.; sorbera, l.a.; leeson, p.a.; castaner, j.;