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【结 构 式】

【分子编号】69461

【品名】(3S,8S,9R,10S,13R,E)-17-hydrazono-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-ol

【CA登记号】

【 分 子 式 】C19H30N2O

【 分 子 量 】302.46

【元素组成】C 75.45% H 10.00% N 9.26% O 5.29%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(IV)

Abiraterone acetate has been synthesized by two related routes.
a) Reaction of dehydroepiandrosterone acetate (Ia) with trifluoromethanesulfonic anhydride and triethylamine in dichloromethane gives the enol triflate (II), which is finally coupled with diethyl(3-pyridyl)borane (III) by means of PdCl2(PPh3)4 in tetrahydrofuran .
b) In an improved procedure, dehydroepiandrosterone (Ib) is converted to the corresponding hydrazone (IV) by treatment with hydrazine hydrate and a catalytic amount of hydrazine sulfate in EtOH. Subsequent reaction of hydrazone (IV) with iodine and 1,1,3,3-tetramethylguanidine (TMG) in THF/Et2O gives the vinyl iodide (V), which undergoes palladium–catalyzed cross coupling with diethyl(3-pyridyl)borane (III) to yield abiraterone (VI). Finally, alcohol (VI) is acetylated using acetic anhydride in pyridine .

1 Potter, G.A., Barrie, S.E., Jarman, M., Rowlands, M.G. Novel steroidal inhibitors of human cytochrome P45017α (17α-hydroxylase-C17,20-lyase): potential agents for the treatment of prostatic cancer. J Med Chem 1995, 38(13): 2463-71.
2 Barrie, S.E., Jarman, M., Potter, G.A. (BTG plc.). 17-Substituted steroids useful in cancer treatment. EP 0633893, GB 2265624, US 5604213, WO 1993020097.
3 Hunt, N.J. (BTG International Ltd). Methanesulfonate salts of abiraterone-3-esters and recovery of salts of abiraterone-3-esters from solution in methyl tert-butyl ether. CA 2576922, EP 1789432, JP 2008510780, US 2007249837, WO 2006021776.
4 Bury, P.S. (BTG International Ltd.). Process for the preparation of 17-Ovinyl-triflates as intermediates. EP 1781683, JP 2008510781, US 2007282109, WO 2006021777.
5 Potter, G.A. and Hardcastle, I.R. (BTG International Ltd). Synthesis of 17-(3-pyridyl) steroids. CA 2170286, EP 0721461, GB 2282377, JP 1997502994, WO 1995009178.
6 Potter, G.A., Hardcastle, I.R., Jarman, M. A convenient, large-scale synthesis of abiraterone acetate [3β-acetoxy-17-(3-pyridyl)androsta-5,16-diene], a potential new drug for the treatment of prostate cancer. Org Prep Proced Int 1997, 29: 123.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(Ia) 20083 Prasterone acetate;3b-Hydroxy-5-androstene-17-one acetate;Dehydroisoandrosterone acetate;Dehydroepiandrosterone 3-acetate;Dehydroepiandrosterone acetate;(3S,8R,9S,10R,13S,14S)-10,13-dimethyl-17-oxo-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate 853-23-6 C21H30O3 详情 详情
(Ib) 11713 Dehydroepiandrosterone;prasterone;(3S,8R,9S,10R,13S,14S)-3-Hydroxy-10,13-dimethyl-1,2,3,4,7,8,9,10,11,12,13,14,15,16-tetradecahydro-17H-cyclopenta[a]phenanthren-17-one 53-43-0 C19H28O2 详情 详情
(II) 20085 (3S,8R,9S,10R,13S,14S)-10,13-dimethyl-17-[[(trifluoromethyl)sulfonyl]oxy]-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate C22H29F3O5S 详情 详情
(III) 20086 3-(diethylboryl)pyridine C9H14BN 详情 详情
(IV) 69461 (3S,8S,9R,10S,13R,E)-17-hydrazono-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-ol C19H30N2O 详情 详情
(V) 69460 (3R,8S,9R,10S,13R)-17-iodo-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-3-ol 32138-69-5 C19H27IO 详情 详情
(VI) 69462 (3R,8S,9R,10S,13R)-10,13-dimethyl-17-(pyridin-3-yl)-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-3-ol C24H31NO 详情 详情
Extended Information