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【结 构 式】 
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【分子编号】37387 【品名】5,6-dihydroxy-2-(methylamino)-3,4-dihydro-1(2H)-naphthalenone 【CA登记号】 |
【 分 子 式 】C11H13NO3 【 分 子 量 】207.22916 【元素组成】C 63.76% H 6.32% N 6.76% O 23.16% |
合成路线1
该中间体在本合成路线中的序号：(XIV)The condensation of 2,3-dimethoxybenzaldehyde (VI) with pyruvic acid (VII) by means of KOH in ethanol/water gives 4-(2,3-dimethoxyphenyl)-2-oxo-3-butenoic acid (VIII), which is reductocondensed with methylamine (IV) by means of H2 over Pd/C in ethanol/ acetic acid to yield 4-(2,3-dimethoxyphenyl)-2-methylamino)butyric acid (IX). Reaction of acid (IX) with benzyl chloroformate (X) and NaOH in water affords the carbamate (XI), which is treated with refluxing SOCl2 to provide 4-[2-(2,3-dimethoxyphenyl)ethyl]-3-methyloxazolidine-2,5-dione (XII). Reaction of oxazolidinone (XII) with AlCl3 in dichloromethane provides 5,6-dimethoxy-2-(methylamino)-1,2,3,4-tetrahydronaphthalen-1-one (XIII), which is reduced with H2 over Pd/C in ethanol containing some methanolic HCl in an autoclave at 80 C to yield N-(5,6-dimethoxy-1,2,3,4-tetrahydronaphthalen-2-yl)-N-methylamine (V). Finally, this compound is demethylated by treatment with AlCl3 in hot toluene. Alternatively, 5,6-dimethoxy-2-(methylamino)-1,2,3,4-tetrahydronaphthalen-1-one (XIII) can first be demethylated with 48% HBr to give 5,6-dihydroxy-2-(methylamino)-1,2,3,4-tetrahydronaphthalen-1-one (XIV), which is then reduced by means of H2 over Pd/C in an autoclave at 80 C.
| 【1】 Castaner, J.; Mealy, N.E.; Bayes, M.; Leeson, P.A.; Nolomirole Hydrochloride. Drugs Fut 2001, 26, 11, 1046. |
| 【2】 Servadio, V.; Ventura, P.; Amari, G.; Chiesi, P.; Del Canale, M.; De Fanti, R. (Chiesi Farmaceutici SpA); A process for the preparation of 5,6-dihydroxy-2-amino-1,2,3,4-tetrahydronaphthalene derivs.. WO 9529147 . |
| 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) | 49435 | 6-(methylamino)-5,6,7,8-tetrahydro-1,2-naphthalenediol | C11H15NO2 | 详情 | 详情 | |
| (IV) | 11021 | Methanamine; Methylamine | 74-89-5 | CH5N | 详情 | 详情 |
| (V) | 37381 | N-(5,6-dimethoxy-1,2,3,4-tetrahydro-2-naphthalenyl)-N-methylamine; 5,6-dimethoxy-N-methyl-1,2,3,4-tetrahydro-2-naphthalenamine | C13H19NO2 | 详情 | 详情 | |
| (VI) | 17615 | 2,3-Dimethoxybenzaldehyde | 86-51-1 | C9H10O3 | 详情 | 详情 |
| (VII) | 24066 | 2-oxopropionic acid | 127-17-3 | C3H4O3 | 详情 | 详情 |
| (VIII) | 37376 | (E)-4-(2,3-dimethoxyphenyl)-2-oxo-3-butenoic acid | C12H12O5 | 详情 | 详情 | |
| (IX) | 37377 | 4-(2,3-dimethoxyphenyl)-2-(methylamino)butyric acid | C13H19NO4 | 详情 | 详情 | |
| (X) | 10101 | Benzyloxycarbonyl chloride; Benzyl chloroformate; 1-[[(Chlorocarbonyl)oxy]methyl]benzene | 501-53-1 | C8H7ClO2 | 详情 | 详情 |
| (XI) | 37378 | 2-[[(benzyloxy)carbonyl](methyl)amino]-4-(2,3-dimethoxyphenyl)butyric acid | C21H25NO6 | 详情 | 详情 | |
| (XII) | 37379 | 4-(2,3-dimethoxyphenethyl)-3-methyl-1,3-oxazolidine-2,5-dione | C14H17NO5 | 详情 | 详情 | |
| (XIII) | 37380 | 5,6-dimethoxy-2-(methylamino)-3,4-dihydro-1(2H)-naphthalenone | C13H17NO3 | 详情 | 详情 | |
| (XIV) | 37387 | 5,6-dihydroxy-2-(methylamino)-3,4-dihydro-1(2H)-naphthalenone | C11H13NO3 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IX)Intramolecular acylation of amino acid (IV), with simultaneous deprotection of the hydroxyl groups using concentrated HBr furnished amino tetralone (IX). The keto group of (IX) was then reduced by hydrogenation in the presence of Pd/C.
| 【1】 Servadio, V.; Ventura, P.; Amari, G.; Chiesi, P.; Del Canale, M.; De Fanti, R. (Chiesi Farmaceutici SpA); A process for the preparation of 5,6-dihydroxy-2-amino-1,2,3,4-tetrahydronaphthalene derivs.. WO 9529147 . |