药物详细合成路线
| Name | Droloxifene;FK-435;K-060;K-21060E | | Chemical Name | (E)-3-[1-[4-[2-(Dimethylamino)ethoxy]phenyl]-2-phenyl-1-butenyl]phenol;(E)-1-[4-(2-Dimethylaminoethoxy)phenyl]-1-(3-hydroxyphenyl)-2-phenylbut-1-ene;(E)-alpha-[p-[2-(Dimethylamino)ethoxy]phenyl]-alpha-ethyl-3-stilbenol | | CAS | 82413-20-5 | | Related CAS | 97752-20-0 (citrate (1:1)), 83647-28-3 (HCl) | | Formula | C26H29NO2 | | Structure |  | | Formula Weight | 387.52653 | | Stage | 中止开发 | | Company | Fujisawa (Originator), Fujisawa Deutschland (Originator), Pfizer (Licensee) | | Activity/Mechanism | Atherosclerosis Therapy, Bone Diseases, Treatment of, Breast Cancer Therapy, CARDIOVASCULAR DRUGS, METABOLIC DRUGS, Oncolytic Drugs, Prevention of Osteoporosis, Treatment of Disorders of the Coronary Arteries and Atherosclerosis, Treatment of Osteoporosis, Selective Estrogen Receptor Modulators (SERM) | | Syn. Route | 1 | | Route 1 | | the reaction of 1-(4-methoxyphenyl)-2-phenylethan-1-one (i) with ethyl bromide (a) gave (ii) in nearly quantitative yield. demethoxylation of (ii) with pyridine hydrochloride gave (iii) in about 70% yield. treatment of (iii) with dimethylaminoethyl chloride (b) gave (iv) in more than 60% yield. reaction of (iv) with 3-(2-tetrahydropyranyloxy)phenylmagnesium bromide (c) gave (v) in about 60% yield. refluxing a solution of (v) in ethanolic hydrochloric acid gave the stereoisomeric e- and z-mixture (via, vib) of the hydrochloric salt. fractional crystallization of the mixture in methanol/ether yielded the pure hydrochloric salt of the e-isomer in 48% yield. conversion of the hydrochloric salt into the free base and treatment of the latter with citric acid yielded the appropriate k-21060e citrate. | | |  | | List of intermediates | No. | | ethyl (z)-3-(2-methoxy-4-pyridinyl)-2-propenoate | (b) | | tert-butyl (1s)-2-[[(1s)-2-hydroxy-1-isobutylhexyl]amino]-1-(1h-imidazol-5-ylmethyl)-2-oxoethylcarbamate | (i) | | (2s)-2-amino-n-[(1s)-2-hydroxy-1-isobutylhexyl]-3-(1h-imidazol-5-yl)propanamide | (a) | | (2s)-2-[(tert-butoxycarbonyl)amino]-3-(1h-imidazol-5-yl)propionic acid | (ii) | | (2s)-6-amino-2-[(tert-butoxycarbonyl)amino]hexanoic acid | (iii) | | l-(-)-n-alpha-boc-amino-epsilon-caprolactam; tert-butyl (3s)-2-oxoazepanylcarbamate | (iv) | | benzyl 2-[(3s)-3-[(tert-butoxycarbonyl)amino]-2-oxoazepanyl]acetate | (c) | | benzyl 2-[(3s)-3-([(2s)-2-[(tert-butoxycarbonyl)amino]propanoyl]amino)-2-oxoazepanyl]acetate | (v) | | benzyl 2-[(3s)-3-[((2s)-2-[[(2s)-2-[(tert-butoxycarbonyl)amino]-3-(1h-indol-3-yl)propanoyl]amino]propanoyl)amino]-2-oxoazepanyl]acetate | (via) | | benzyl 2-((3s)-3-[[(2s,5s,8s)-8-(3-amino-3-oxopropyl)-5-(1h-indol-3-ylmethyl)-2,12,12-trimethyl-4,7,10-trioxo-11-oxa-3,6,9-triazatridec-1-anoyl]amino]-2-oxoazepanyl)acetate | (vib) | | | Reference 1: schickaneder, h.; loser, r.; grill, h. (klinge pharma gmbh); 1,1,2-triphenylbut-1-ene derivatives. de 3046719; ep 0054168; us 5047431 . Reference 2: loser, r.; seibel, k.; janiak, p.-st.; k-21060 e. drugs fut 1984, 9, 3, 186. |
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