【结 构 式】 |
【分子编号】55860 【品名】(2R)-2-[(methoxycarbonyl)amino]-3-phenylpropanoic acid 【CA登记号】 |
【 分 子 式 】C11H13NO4 【 分 子 量 】223.22856 【元素组成】C 59.19% H 5.87% N 6.27% O 28.67% |
合成路线1
该中间体在本合成路线中的序号:(II)D-Phenylalanine (I) was protected as the methyl carbamate (II) by acylation with methyl chloroformate under Schotten-Baumann conditions. The N-methoxy amide (III) was then prepared by coupling of (II) with O-methyl hydroxylamine in the presence of EDC. Cyclization of (III) to the N-methoxy quinolinone (IV) was accomplished by treatment with bis(trifluoroacetoxy)iodobenzene in the presence of trifluoroacetic acid. Simultaneous reduction of the N-methoxy lactam and carbamate functions of (IV) by means of borane-methyl sulfide complex provided diamine (V). The aliphatic amino group of (V) was then selectively protected as the benzyl carbamate (VI) by using N-(benzyloxycarbonyloxy)succinimide at -40 C. Reaction of (VI) with phosgene, followed by treatment of the intermediate carbamoyl chloride with O-methyl hydroxylamine gave rise to the N-methoxy urea derivative (VII). This was cyclized with bis(trifluoroacetoxy)iodobenzene to the imidazoquinolinone (VIII). The N-methoxy and N-benzyloxycarbonyl groups of (VIII) were then removed by hydrogenolysis in the presence of Pearlman's catalyst, and the title compound was finally converted to the corresponding maleate salt.
【1】 Romero, A.G.; et al.; Synthesis of the selective D2 receptor agonist PNU-95666E from D-phenylalanine using a sequential oxidative cyclization strategy. J Org Chem 1997, 62, 19, 6582. |
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) | 11703 | D-Phenylalanine; (R)-Phenylalanine | 673-06-3 | C9H11NO2 | 详情 | 详情 |
(II) | 55860 | (2R)-2-[(methoxycarbonyl)amino]-3-phenylpropanoic acid | C11H13NO4 | 详情 | 详情 | |
(III) | 55861 | methyl (1R)-1-benzyl-2-(methoxyamino)-2-oxoethylcarbamate | C12H16N2O4 | 详情 | 详情 | |
(IV) | 55862 | methyl (3R)-1-methoxy-2-oxo-1,2,3,4-tetrahydro-3-quinolinylcarbamate | C12H14N2O4 | 详情 | 详情 | |
(V) | 55863 | N-methyl-N-[(3R)-1,2,3,4-tetrahydro-3-quinolinyl]amine; (3R)-N-methyl-1,2,3,4-tetrahydro-3-quinolinamine | C10H14N2 | 详情 | 详情 | |
(VI) | 55864 | benzyl methyl[(3R)-1,2,3,4-tetrahydro-3-quinolinyl]carbamate | C18H20N2O2 | 详情 | 详情 | |
(VII) | 55865 | benzyl (3R)-1-[(methoxyamino)carbonyl]-1,2,3,4-tetrahydro-3-quinolinyl(methyl)carbamate | C20H23N3O4 | 详情 | 详情 | |
(VIII) | 55866 | benzyl (5R)-1-methoxy-2-oxo-1,2,5,6-tetrahydro-4H-imidazo[4,5,1-ij]quinolin-5-yl(methyl)carbamate | C20H21N3O4 | 详情 | 详情 |