【结 构 式】 |
【分子编号】10066 【品名】(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 【CA登记号】 |
【 分 子 式 】C11H14BrN 【 分 子 量 】240.1429 【元素组成】C 55.02% H 5.88% Br 33.27% N 5.83% |
合成路线1
该中间体在本合成路线中的序号:(II)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 |