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【结 构 式】

【分子编号】36637

【品名】(1R,2R)-1-(methylamino)-1,2,3,4-tetrahydro-2-naphthalenol

【CA登记号】

【 分 子 式 】C11H15NO

【 分 子 量 】177.24624

【元素组成】C 74.54% H 8.53% N 7.9% O 9.03%

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:(XXIV)

The bromination of tetraline (XIX) with Br2 in hexane gives trans-1,2-dibromotetraline (XX), which by treatment with H2O and NaHCO3 yields trans-2-bromotetralin-1-ol (XXI) [also obtained by reaction of 1,2-dihydronaphthalene (XXII) with 1,3-dibromo-5,5-dimethylhydantoin (DBDH) and perchloric acid]. The reaction of (XXI) with methylamine affords the intermediate epoxide (XXIII), which without isolation with more methylamine gives trans 1-(methylamino) tetralin-2-ol as a racemic mixture rac-(XXIV). The optical resolution of this mixture with (+)-L-tartaric acid yields the desired enantiomer (R,R)(XXIV), which is condensed with 2-bromoacetaldehyde dimethyl acetal (XXV) by means of K2CO3 in acetonitrile furnishing the chiral tertiary amine (XXVI). The cyclization of (XXVI) with BuLi and TsCl provides the intermediate aziridinium salt (XXVII), which without isolation, is condensed with 4-chloro-3-methoxyphenyl-magnesium bromide (X) in THF to give the chiral tertiary amine (XXVIII). The cyclization of (XXVIII) by means of methanesulfonic acid yields the chiral tetracyclic compound (XXIX), which is hydrogenated by means of BH3/t-Bu-NH2 to afford (6aS,13bR)(VIII). Finally, this compound is demethylated with 48% HBr in acetic acid. The chiral secondary amine (XXVI) can also be obtained as follows: The enantioselective epoxidation of 1,2-dihydronaphthalene (XXII) by means of a chiral manganese catalyst and sodium hypochlorite gives the chiral epoxide (1S,2R)(XXIII), which is cleaved with 2-(methylamino)acetaldehyde dimethylacetal (XXX) at 95 C in a pressure vessel to yield the desired chiral secondary amine (XXVI).

1 Berger, J.G.; Clader, J.W.; Chang, W.K.; Gold, E.H. (Schering Corp.); Fused benzazepines. EP 0230270; EP 0254737; JP 1988502348; WO 8704430 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
11021 Methanamine; Methylamine 74-89-5 CH5N 详情 详情
(VIII) 31779 (3aS,9bR)-12-chloro-11-methoxy-3-methyl-2,3,3a,4,5,9b-hexahydro-1H-naphtho[1,2-a][3]benzazepine; (3aS,9bR)-12-chloro-3-methyl-2,3,3a,4,5,9b-hexahydro-1H-naphtho[1,2-a][3]benzazepin-11-yl methyl ether C20H22ClNO 详情 详情
(X) 36324 methyl 2-chloro-3-[4-[4-(2-chloro-3-methoxy-3-oxopropyl)benzyl]phenyl]propanoate C21H22Cl2O4 详情 详情
(XIX) 36632 1,2,3,4-tetrahydronaphthalene 119-64-2 C10H12 详情 详情
(XX) 36633 (1S,2S)-1,2-dibromo-1,2,3,4-tetrahydronaphthalene C10H10Br2 详情 详情
(XXI) 36634 (1S,2S)-2-bromo-1,2,3,4-tetrahydro-1-naphthalenol C10H11BrO 详情 详情
(XXII) 36635 1,2-dihydronaphthalene 447-53-0 C10H10 详情 详情
(XXIII) 36636 (1aR,7bS)-1a,2,3,7b-tetrahydronaphtho[1,2-b]oxirene C10H10O 详情 详情
(XXIV) 36637 (1R,2R)-1-(methylamino)-1,2,3,4-tetrahydro-2-naphthalenol C11H15NO 详情 详情
(XXV) 13183 2-Bromo-1,1-dimethoxyethane; 2-Bromo-1-methoxyethyl methyl ether; Bromoacetaldehyde dimethyl acetal 7252-83-7 C4H9BrO2 详情 详情
(XXVI) 36638 (1R,2R)-1-[(2,2-dimethoxyethyl)(methyl)amino]-1,2,3,4-tetrahydro-2-naphthalenol C15H23NO3 详情 详情
(XXVII) 36639   n/a AB 详情 详情
(XXVIII) 36640 N-[(1S,2S)-1-(4-chloro-3-methoxyphenyl)-1,2,3,4-tetrahydro-2-naphthalenyl]-N-(2,2-dimethoxyethyl)-N-methylamine; (1S,2S)-1-(4-chloro-3-methoxyphenyl)-N-(2,2-dimethoxyethyl)-N-methyl-1,2,3,4-tetrahydro-2-naphthalenamine C22H28ClNO3 详情 详情
(XXIX) 36641 (3aS,9bR)-12-chloro-3-methyl-3a,4,5,9b-tetrahydro-3H-naphtho[1,2-a][3]benzazepin-11-yl methyl ether; (3aS,9bR)-12-chloro-11-methoxy-3-methyl-3a,4,5,9b-tetrahydro-3H-naphtho[1,2-a][3]benzazepine C20H20ClNO 详情 详情
(XXX) 36650 2,2-dimethoxy-N-methyl-1-ethanamine;1,1-Dimethoxy-2-(methylamino)-ethane;Methylaminoacetaldehyde dimethyl acetal;N-(2,2-dimethoxyethyl)-N-methylamine 122-07-6 C5H13NO2 详情 详情
Extended Information