【结 构 式】 |
【分子编号】16072 【品名】2',5'-Dioxo-3,4-dihydro-2H-spiro[1-benzopyran-4,4'-imidazolidin]-2-ylcarboxylic acid 【CA登记号】 |
【 分 子 式 】C12H10N2O5 【 分 子 量 】262.22188 【元素组成】C 54.97% H 3.84% N 10.68% O 30.51% |
合成路线1
该中间体在本合成路线中的序号:(XV)2) The cyclization of 6-fluoro-3,4-dihydro-2H-1-benzopyran-2-carboxylic acid (IV) with KCN and ammonium carbonate in hot water (80-90 C) gives 6-fluoro-2',5'-dioxospiro[3,4-dihydro-2H-1-benzopyran-4,4'-imidazolidine]-2-carboxylic acid (X) as a (5:1)-mixture of the (RS,RS)- and (RS,SR)-diastereomers. This mixture is treated with SiCl4 and dry ammonia in pyridine, yielding the corresponding (5:1)-mixture of amides (XI), which is separated by recrystallization, affording the (RS,RS)-diastereomer (XII) as a pure compound. The optical resolution of (XII) with N-methylquininium hydroxide (XIII) and crystallization gives the (2S,4S)-isomer as the N-methylquininium salt (XIV), which is finally treated with 1N aqueous HCl in ethanol/water.
【1】 Mealy, N.; Castaner, J.; SNK-860. Drugs Fut 1996, 21, 3, 261. |
【2】 Kurono, M.; Kondo, Y.; Yamaguchi, T.; Miura, K.; Usui, T.; Terada, N.; Asano, K.; Mizuno, K.; Matsubara, A.; Kato, N.; Sawai, K.; Unno, R.; Ozawa, H.; Fukushima, M. (Sanwa Kagaku Kenkyusho Co., Ltd.); Hydantoin derivs. for treating complications of diabetes. EP 0264586; JP 1988057588; JP 1988126881; JP 1988250373; US 4861792; US 4978758; US 5447946 . |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(IV) | 16060 | 6-fluoro-4-oxo-2-chromanecarboxylic acid | C10H7FO4 | 详情 | 详情 | |
(X) | 16067 | 6-Fluoro-2',5'-dioxo-3,4-dihydro-2H-spiro[1-benzopyran-4,4'-imidazolidin]-2-ylcarboxylic acid | C12H9FN2O5 | 详情 | 详情 | |
(XI) | 16068 | (rac)-(6-Fluoro-2',5'-dioxo-3,4-dihydro-2H-spiro[1-benzopyran-4,4'-imidazolidin]-2-ylcarboxamide) | C12H10FN3O4 | 详情 | 详情 | |
(XII) | 64700 | C12H10FN3O4 | 详情 | 详情 | ||
(XIII) | 64698 | 5-ethenyl-2-{hydroxy[6-(methyloxy)-4-quinolinyl]methyl}-1-methyl-1-azoniabicyclo[2.2.2]octane hydroxide | C21H28N2O3 | 详情 | 详情 | |
(XIV) | 64699 | C33H38FN5O7 | 详情 | 详情 | ||
(XV) | 16072 | 2',5'-Dioxo-3,4-dihydro-2H-spiro[1-benzopyran-4,4'-imidazolidin]-2-ylcarboxylic acid | C12H10N2O5 | 详情 | 详情 |