CI-201678(HCl), Cpd-201678, 201678

磷酸二氢(3β,5β,14xi,22R)-3,14,25-三羟基-6-羰基胆甾-7-烯-22-酯Chemical Name: (-)-(4S,5aR)-5-Ethyl-9,10-dihydroxy-4-propyl-4,5,5a,6-tetrahydrodibenz[cd,f]indole
CAS No. 82166-77-6, 82188-32-7 ((4S)-trans-isomer, HBr), 82188-33-8 ((4S)-trans-isomer, HCl), 82122-86-9 (rac-trans-isomer)
项目整合开发状态: Phase II
项目研究机构: Novartis (Originator)
合成路线:The acylation of 9-ethylamino-8-bromo-3,4-dimethoxyphenanthrene (I) with butyryl chloride (II) in CH2Cl2 gives 9-(N-ethyl-N-butyrylamino)-8-bromo-3,4-dimethoxyphenanthrene (III),which is cyclized by means of butyllithium in THF yielding 5-ethyl-4,5-dihydro-9,10-dimethoxy-4-n-propyldibenz[cd,f]indole-4-ol (IV).The reduction of (IV) with Zn-HgCl2 in refluxing ethanol water affords 5-ethyl-4,5,5a,6-tetrahydro-9,10-diethoxy-4-n-propyldibenz[cd,f]indole (V),which is finally demethylated by means of refluxing aqueous 47% HBr.

合成路线:The reaction of 3,4-dimethoxyphenanthrene-9-carboxylic acid (VI) first with trifluoroacetic anhydride and then with sodium azide gives 9-amino-3,4-dimethoxyphenanthrene (VII),which is acetylated with acetyl chloride in CH2Cl2 yielding 9-acetylamino-3,4-dimethoxyphenanthrene (VIII).The reduction of (VIII) with diborane in THF affords 9-ethylamino-3,4-dimethoxyphenanthrene (IX),which is cyclized with CO2 by means of n-butyllithium in THF affording 5-ethyl-4,5-dihydro-9,10-dimethoxy-4-oxodibenz[cd,f]indole (X).Finally,this compound is submitted to a Grignard synthesis with propylmagnesium bromide (A) in THF to give (IV),already obtained.