MDL-10222F(undefined isomer), MDL-101986, -Drug Synthesis Database

【结构式】

【药物名称】MDL-10222F(undefined isomer), MDL-101986

【化学名称】(E)-N'-[4-(2-Chloro-1,2-diphenylvinyl)phenyl]-N,N-diethyl-1,2-ethanediamine citrate (1:1)

【CA登记号】179552-06-8, 179552-05-7 (free base), 179552-10-4 (monoHCl), 155519-89-4 (undefined isomer)

【分子式】C₃₂H₃₇ClN₂O₇

【分子量】597.11389

【开发单位】Aventis Pharma (Originator)

【药理作用】Bone Diseases, Treatment of, ENDOCRINE DRUGS, Gynecological Disorders, Treatment of , METABOLIC DRUGS, Treatment of Osteoporosis, Treatment of Postmenopausal Syndrome , Selective Estrogen Receptor Modulators (SERM)

合成路线1 合成路线2

合成路线1

The reaction of 4-aminobenzophenone (I) with benzylmagnesium bromide (II) in ether gives the carbinol (III), which by reaction with acetic anhydride in hot pyridine yields the olefinic acetamide (IV). The chlorination of (IV) with Cl2 in CCl4 followed by refluxing in the same solvent affords the chlorovinyl acetamide (V), which is alkylated at the amidic nitrogen with 2-chloroethyl(diethyl)amine (VI) by means of KOH in refluxing acetone giving the disubstituted acetamide (VII). Finally, the deacetylation of (VII) with hot 10% HCl and salification with citric acid affords the target compound.

参考文献中间体

【1】 Bitonti, A.J.; Baumann, R.J. (Merrell Pharmaceuticals, Inc.); Non-metabolizable clomiphene analogs for treatment of tamoxifen-resistant tumors. EP 0660821; JP 1997500863; WO 9406762 .

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)	28307	(4-aminophenyl)(phenyl)methanone	1137-41-3	C₁₃H₁₁NO	详情	详情
(II)	28308	benzyl(bromo)magnesium; benzylmagnesium bromide	1589-82-8	C₇H₇BrMg	详情	详情
(III)	28309	1-(4-aminophenyl)-1,2-diphenyl-1-ethanol		C₂₀H₁₉NO	详情	详情
(IV)	28310	N-[4-[(Z)-1,2-diphenylethenyl]phenyl]acetamide		C₂₂H₁₉NO	详情	详情
(V)	28311	N-[4-[(E)-2-chloro-1,2-diphenylethenyl]phenyl]acetamide		C₂₂H₁₈ClNO	详情	详情
(VI)	16194	2-chloro-N,N-diethyl-1-ethanamine; N-(2-chloroethyl)-N,N-diethylamine	100-35-6	C₆H₁₄ClN	详情	详情
(VII)	28312	N-[4-[(E)-2-chloro-1,2-diphenylethenyl]phenyl]-N-[2-(diethylamino)ethyl]acetamide		C₂₈H₃₁ClN₂O	详情	详情

合成路线2

The acetylation of 4-aminobenzophenone (I) with acetic anhydride and TEA in dichloromethane gives the acetamide (II), which is N-alkylated with 2-chlorethyl(diethyl)amine (III) by means of KOH in refluxing acetone yielding the disubstituted acetamide (IV). The reaction of the ketonic group of (IV) with benzylphosphonic acid diethyl ester (V) by means of butyllithium and benzenesulfonyl chloride in THF affords the chlorovinyl acetamide (VI), which is finally hydrolyzed with HCl and salified with citric acid to provide the target compound.

参考文献中间体

【1】 Bitonti, A.J. (Aventis Pharmaceuticals, Inc.); Method of using triaryl-ethylene derivs. in the treatment and prevention of osteoporosis. US 5691384; WO 9616646 .

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)	28307	(4-aminophenyl)(phenyl)methanone	1137-41-3	C₁₃H₁₁NO	详情	详情
(II)	28313	N-(4-benzoylphenyl)acetamide		C₁₅H₁₃NO₂	详情	详情
(III)	16194	2-chloro-N,N-diethyl-1-ethanamine; N-(2-chloroethyl)-N,N-diethylamine	100-35-6	C₆H₁₄ClN	详情	详情
(IV)	28314	N-(4-benzoylphenyl)-N-[2-(diethylamino)ethyl]acetamide		C₂₁H₂₆N₂O₂	详情	详情
(V)	28315	diethyl benzylphosphonate	1080-32-6	C₁₁H₁₇O₃P	详情	详情
(VI)	28312	N-[4-[(E)-2-chloro-1,2-diphenylethenyl]phenyl]-N-[2-(diethylamino)ethyl]acetamide		C₂₈H₃₁ClN₂O	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(1)