Bicalutamide, ICI-176334, Raffolutil, Casodex, -Drug Synthesis Database

【结构式】

【药物名称】Bicalutamide, ICI-176334, Raffolutil, Casodex

【化学名称】(±)-4-[3-(4-Fluorophenylsulfonyl)-2-hydroxy-2-methylpropionamido]-2-(trifluoromethyl)benzonitrile

【CA登记号】90357-06-5

【分子式】C₁₈H₁₄F₄N₂O₄S

【分子量】430.38088

【开发单位】AstraZeneca (Originator)

【药理作用】Oncolytic Drugs, Prostate Cancer Therapy, Androgen Receptor Antagonists

合成路线1 合成路线2

合成路线1

Coupling of methacryloyl chloride (I) with substituted aniline (II) in dimethylacetamide yields amide (III), which is then converted into the epoxy derivative (IV) by oxidation with m-chloroperbenzoic acid (mCPBA) and 4-methyl-2,6-di-tert-butylphenol (A) in refluxing 1,1,1-trichloroethane. Condensation of (IV) with thiol (V) by means of NaH in THF provides fluorophenylthio derivative (VI), which is finally oxidized with mCPBA in CH2Cl2 to furnish the desired compound trichloroethane.

参考文献中间体

【1】 Tucker, H. (AstraZeneca plc); Amide derivs.. EP 0100172; JP 1990131462; US 4636505 .
【2】 Crook, J.W.; Tucker, H.; Chesterson, G.J.; Nonsteroidal antiandrogens. Synthesis and structure-activity relationships of 3-substituted derivatives of 2-hydroxypropionanilides. J Med Chem 1988, 31, 5, 954.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	48072	2,6-di(tert-butyl)-4-methylphenol	128-37-0	C₁₅H₂₄O	详情	详情
(I)	33553	2-methylacryloyl chloride	920-46-7	C₄H₅ClO	详情	详情
(II)	18743	4-amino-2-(trifluoromethyl)benzonitrile；5-Amino-2-cyanobenzotrifluoride	654-70-6	C₈H₅F₃N₂	详情	详情
(III)	48071	N-[4-cyano-3-(trifluoromethyl)phenyl]-2-methylacrylamide		C₁₂H₉F₃N₂O	详情	详情
(IV)	48074	N-[4-cyano-3-(trifluoromethyl)phenyl]-2-methyl-2-oxiranecarboxamide		C₁₂H₉F₃N₂O₂	详情	详情
(V)	22971	4-fluorobenzenethiol; 4-fluorophenylhydrosulfide; 4-Fluorothiophenol	371-42-6	C₆H₅FS	详情	详情
(VI)	48073	N-[4-cyano-3-(trifluoromethyl)phenyl]-3-[(4-fluorophenyl)sulfanyl]-2-hydroxy-2-methylpropanamide		C₁₈H₁₄F₄N₂O₂S	详情	详情

合成路线2

The reaction of 4-amino-2-(trifluoromethyl)benzonitrile (I) with 2-oxopropionic acid (II) by means of SOCl2 gives the corresponding amide (III), which is finally condensed with the methyl sulfone (IV) by means of BuLi in THF.

参考文献中间体

【1】 Ekwuribe, N.N.; James, K.D.; A two-step synthesis of the anti-cancer drug (R,S)-bicalutamide. Synthesis (Stuttgart) 2002, 7, 850.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	18743	4-amino-2-(trifluoromethyl)benzonitrile；5-Amino-2-cyanobenzotrifluoride	654-70-6	C₈H₅F₃N₂	详情	详情
(II)	24066	2-oxopropionic acid	127-17-3	C₃H₄O₃	详情	详情
(III)	58597	N-[4-cyano-3-(trifluoromethyl)phenyl]-2-oxopropanamide		C₁₁H₇F₃N₂O₂	详情	详情
(IV)	46256	4-fluorophenyl methyl sulfone; (4-fluorophenyl)(methyl)dioxo-lambda(6)-sulfane		C₇H₇FO₂S	详情	详情

Extended Information