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【结 构 式】

【分子编号】10071

【品名】N-[(1R,4S)-7-Bromo-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-naphthalenyl]-N-methylformamide

【CA登记号】

【 分 子 式 】C18H16BrCl2NO

【 分 子 量 】413.14058

【元素组成】C 52.33% H 3.9% Br 19.34% Cl 17.16% N 3.39% O 3.87%

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:(VII)

A new synthesis of [7-3H]-sertraline has been described: The optical resolution of 7-bromo-1-(methylamino)tetraline (I) with N-acetyl-D-phenylalanine gives the (R)-isomer (II), which is acylated with formic acid - acetic anhydride to the formamide (III). The oxidation of (III) with KMnO4 in acetone - water yields 6-bromo-4(R)-(methylamino)-1,2,3,4-tetrahydronaphthalen-1-one (IV), which, by a Grignard condensation with 3,4-dichlorophenylmagnesium bromide (V) in ether - toluene, affords 6-bromo-1(S)-(3,4-dichlorophenyl)-4(R)-(N-methylformamido)-1,2,3,4-tetrahydronaphthalen-1-ol (VI). The reduction of (VI) with triethylsilane tetrafluoroborate in dichloromethane gives 6-bromo-1(S)-(3,4-dichlorophenyl)-4(R)-(N-methylformamido)tetraline (VII), which is hydrolyzed with HCl in isopropanol to the corresponding methylamine (VIII). Oxidation of (VIII) with NaClO NaOCH3 in methanol - water yields the imine (IX), which is reduced with NaBH4 in THF - methanol to 6-bromo-1(S)-(3,4-dichlorophenyl)-4(S)-(methylamino)tetraline (X), along with starting (VIII). After separation by column chromatography, (X) is reduced with H2 over Pd/C or with T2 over Pd/C in THF containing triethylamine.

1 Williams, M.T.; Welch, W.M.; Synthesis of 7-3H-(IS,4S)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-N-methyl-I-naphthalenamine hydrochloride (7-3H-sertraline). J Label Compd Radiopharm 1993, 33, 2, 119.
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) 10065 N-(7-Bromo-1,2,3,4-tetrahydro-1-naphthalenyl)-N-methylamine; 7-Bromo-N-methyl-1,2,3,4-tetrahydro-1-naphthalenamine C11H14BrN 详情 详情
(II) 10066 (1R)-7-Bromo-N-methyl-1,2,3,4-tetrahydro-1-naphthalenamine; N-[(1R)-7-Bromo-1,2,3,4-tetrahydro-1-naphthalenyl]-N-methylamine C11H14BrN 详情 详情
(III) 10067 N-[(1R)-7-Bromo-1,2,3,4-tetrahydro-1-naphthalenyl]-N-methylformamide C12H14BrNO 详情 详情
(IV) 10068 N-[(1R)-7-Bromo-4-oxo-1,2,3,4-tetrahydro-1-naphthalenyl]-N-methylformamide C12H12BrNO2 详情 详情
(V) 10069 Bromo(3,4-dichlorophenyl)magnesium 79175-35-2 C6H3BrCl2Mg 详情 详情
(VI) 10070 N-[(1R,4S)-7-Bromo-4-(3,4-dichlorophenyl)-4-hydroxy-1,2,3,4-tetrahydro-1-naphthalenyl]-N-methylformamide C18H16BrCl2NO2 详情 详情
(VII) 10071 N-[(1R,4S)-7-Bromo-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-naphthalenyl]-N-methylformamide C18H16BrCl2NO 详情 详情
(VIII) 10072 N-[(1R,4S)-7-Bromo-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-naphthalenyl]-N-methylamine; (1R,4S)-7-Bromo-4-(3,4-dichlorophenyl)-N-methyl-1,2,3,4-tetrahydro-1-naphthalenamine C17H16BrCl2N 详情 详情
(IX) 10073 N-[(4S)-7-Bromo-4-(3,4-dichlorophenyl)-3,4-dihydro-1(2H)-naphthalenylidene]methanamine; N-[(4S)-7-Bromo-4-(3,4-dichlorophenyl)-3,4-dihydro-1(2H)-naphthalenylidene]-N-methylamine C17H14BrCl2N 详情 详情
(X) 10074 N-[(1S,4S)-7-Bromo-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-naphthalenyl]-N-methylamine; (1S,4S)-7-Bromo-4-(3,4-dichlorophenyl)-N-methyl-1,2,3,4-tetrahydro-1-naphthalenamine C17H16BrCl2N 详情 详情
Extended Information