【结 构 式】 |
【分子编号】63083 【品名】(+)9-amino-8-hydroxy-2,3,5,6,7,8-hexahydro-1H-cyclopenta[b]quinolin-1-one 【CA登记号】 |
【 分 子 式 】C12H14N2O2 【 分 子 量 】218.25544 【元素组成】C 66.04% H 6.47% N 12.84% O 14.66% |
合成路线1
该中间体在本合成路线中的序号:(V)The synthesis of two dihydroxylated metabolites of NIK-247 has been reported: Two diastereomeric isomers 9-amino-2,3,5,6,7,8-hexahydro-1H-cyclopenta[b]quinoline-1,8-diol (VI) and (VII) have been synthesized as follows. The oxidation of 2,3,5,6,7,8-hexahydro-1H-cyclopenta[b]quinolin-9-amine (I) with CrO3.H2SO4 gives 9-amino-2,3,5,6,7,8-hexahydro-1H-cyclopenta[b]quinoline-1,8-dione (II), which is selectively reduced with 1 equivalent of NaBH4 yielding a mixture of the two hydroxyketones (III) and (IV), separated by crystallization. The optical resolution of (III) with (-)-di-p-toluyltartaric acid affords the pre (+)-isomer (V), which is further reduced with NaBH4 to afford a diastereomeric mixture of the 1,8-diols (VI) and (VII), which is separated by HPLC over Chiracel OG in n-hexane ethanol (9:1).
【1】 Komatsu, T.; Yano, M.; Iwamoto, M.; Kobayashi, M.; Suzuki, K.; Synthesis of estimated metabolites of 9-amino-2,3,5,6,7,8-hexahydro-1H-cyclopenta[b]quinoline monohydrochloride monohydrate (NIK-247). II. Synthesis of dihydroxylated metabolites. Yakugaku Zasshi 1995, 115, 12, 1022. |
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) | 11256 | 2,3,5,6,7,8-Hexahydro-1H-cyclopenta[b]quinolin-9-amine; 2,3,5,6,7,8-Hexahydro-1H-cyclopenta[b]quinolin-9-ylamine | C12H16N2 | 详情 | 详情 | |
(II) | 11257 | 9-Amino-2,3,6,7-tetrahydro-1H-cyclopenta[b]quinoline-1,8(5H)-dione | C12H12N2O2 | 详情 | 详情 | |
(III) | 11258 | 9-Amino-8-hydroxy-2,3,5,6,7,8-hexahydro-1H-cyclopenta[b]quinolin-1-one | C12H14N2O2 | 详情 | 详情 | |
(IV) | 11259 | 9-Amino-1-hydroxy-1,2,3,5,6,7-hexahydro-8H-cyclopenta[b]quinolin-8-one | C12H14N2O2 | 详情 | 详情 | |
(V) | 63083 | (+)9-amino-8-hydroxy-2,3,5,6,7,8-hexahydro-1H-cyclopenta[b]quinolin-1-one | C12H14N2O2 | 详情 | 详情 | |
(VI) | 11261 | 9-Amino-2,3,5,6,7,8-hexahydro-1H-cyclopenta[b]quinoline-1,8-diol | C12H16N2O2 | 详情 | 详情 | |
(VII) | 63084 | 9-amino-2,3,5,6,7,8-hexahydro-1H-cyclopenta[b]quinoline-1,8-diol | C12H16N2O2 | 详情 | 详情 |