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【结 构 式】

【分子编号】65068

【品名】2-(4-{[(2R)-3,4-dihydro-2H-chromen-2-ylmethyl]amino}butyl)-1H-1,2-benzisothiazole-1,1,3(2H)-trione

【CA登记号】

【 分 子 式 】C21H24N2O4S

【 分 子 量 】400.49864

【元素组成】C 62.98% H 6.04% N 6.99% O 15.98% S 8.01%

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:

The synthesis of BAY x 3702 was carried out as outlined: Chroman-2-carboxylic acid (I) was activated with thionyl chloride. The acid chloride (II) was treated with (S)-phenethylamine (III), affording a (1:1)-mixture of diastereomers. Fractional crystallization from ethanol gave the isomer (IV) in high diastereomerical purity; basic epimerization of the undesired diastereomer is feasible. The amide (IV) was reduced with diborane in THF, yielding the amine (V), which was submitted to catalytic hydrogenation over palladium-on-charcoal. The resulting optically pure (R)-2-aminomethyl chroman (VI) was alkylated with 4-bromobutyl saccharin (VII), which is easily available from saccharin sodium and 1,4-dibromobutane. BAY x 3702 was isolated as the hydrochloride salt. White, odorless crystals, m.p. 195 C, alpha(20,D) -42.2 (c 0.9, CHCl3). BAY x 3702 is soluble in water (2.1 g/100 ml), acetone (2.2 g/100 ml) and DMSO. The solid substance is heat-stable, nonhygroscopic and nonsensitive to light. It is unstable in alkaline medium (hydrolysis), sensitive to hydrolysis in aqueous dilute solutions/suspensions at weak acidic and neutral pH, but stable in acidic medium (pH less than or equal to 4). The UV spectrum shows maxima at 272 and 279 nm. BAY x 3702 can be assayed by HPLC.

1 Opitz, W.; Heine, H-G.; Mauler, F.; Schohe-Loop, R.; Maertins, T.; Jork, R.; Dietrich, H.; Glaser, T.; Horvath, E.; Scherling, D.; De Vry, J.; Bay-x-3702. Drugs Fut 1997, 22, 4, 341.
2 Junge, B.; Schohe, R.; Seidel, P.-R.; Glaser, T.; Traber, J.; Benz, U.; Schuurman, T.; De Vry, J.-M.-V. (Bayer AG); Substd. amino methyl tetralines, and their heterocyclic analogous cpds. EP 0352613; JP 1990096552; US 5137901; US 5506246 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
11883 1,4-Dibromobutane; 1,4-Butylene bromide 110-52-1 C4H8Br2 详情 详情
33704 1,1-Dioxide-1,2-benzisothiazol-3(2H)-one, sodium salt; 1,2-Benzisothiazol-3(2H)-one, 1,1-dioxide, sodium salt (1:1) 38279-26-4 C7H4NNaO3S 详情 详情
65068 2-(4-{[(2R)-3,4-dihydro-2H-chromen-2-ylmethyl]amino}butyl)-1H-1,2-benzisothiazole-1,1,3(2H)-trione C21H24N2O4S 详情 详情
(I) 17037 2-chromanecarboxylic acid C10H10O3 详情 详情
(II) 17038 2-chromanecarbonyl chloride C10H9ClO2 详情 详情
(IV) 17040 (2R)-N-[(1S)-1-phenylethyl]-3,4-dihydro-2H-chromene-2-carboxamide C18H19NO2 详情 详情
(V) 17041 (1S)-N-[(2R)-3,4-dihydro-2H-chromen-2-ylmethyl]-1-phenyl-1-ethanamine; N-[(2R)-3,4-dihydro-2H-chromen-2-ylmethyl]-N-[(1S)-1-phenylethyl]amine C18H21NO 详情 详情
(VI) 17042 (2R)-3,4-dihydro-2H-chromen-2-ylmethanamine; (2R)-3,4-dihydro-2H-chromen-2-ylmethylamine C10H13NO 详情 详情
(VII) 17043 2-(4-bromobutyl)-1H-1,2-benzisothiazole-1,1,3(2H)-trione C11H12BrNO3S 详情 详情
Extended Information