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【结 构 式】 
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【分子编号】57379 【品名】(2R)-2-[(3,5-dimethylbenzoyl)(methyl)amino]-3-[4-(1H-pyrrol-1-yl)phenyl]propanoic acid 【CA登记号】 |
【 分 子 式 】C23H24N2O3 【 分 子 量 】376.45524 【元素组成】C 73.38% H 6.43% N 7.44% O 12.75% |
合成路线1
该中间体在本合成路线中的序号：(IX)Esterification of 4-nitro-D-phenylalanine (I) with HCl/MeOH provides the amino ester (II). This is subsequently acylated with 3,5-dimethylbenzoyl chloride (III), yielding amide (IV). Alkylation of amide (IV) by means of iodomethane and NaH affords the N-methyl amide (V). The nitro group of (V) is then reduced to amine (VI) by catalytic hydrogenation over Pd/C. Clauson-Kaas condensation of amine (VI) with 2,5-dimethoxytetrahydrofuran (VII) leads to the pyrrole derivative (VIII). The methyl ester function of (VIII) is then hydrolyzed with LiOH to provide the carboxylic acid (IX).
| 【1】 Ksander, G.M.; Kukkola, P.J.; Robinson, L.A. (Novartis AG); N-aroylamino acid amides as endothelin inhibitors. EP 0821670; JP 1999505522; WO 9633170 . |
| 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) | 57380 | (2R)-2-amino-3-(4-nitrophenyl)propanoic acid | C9H10N2O4 | 详情 | 详情 | |
| (II) | 57381 | methyl (2R)-2-amino-3-(4-nitrophenyl)propanoate | C10H12N2O4 | 详情 | 详情 | |
| (III) | 57374 | 3,5-dimethylbenzoyl chloride | C9H9ClO | 详情 | 详情 | |
| (IV) | 57375 | methyl (2R)-2-[(3,5-dimethylbenzoyl)amino]-3-(4-nitrophenyl)propanoate | C19H20N2O5 | 详情 | 详情 | |
| (V) | 57376 | methyl (2R)-2-[(3,5-dimethylbenzoyl)(methyl)amino]-3-(4-nitrophenyl)propanoate | C20H22N2O5 | 详情 | 详情 | |
| (VI) | 57377 | methyl (2R)-3-(4-aminophenyl)-2-[(3,5-dimethylbenzoyl)(methyl)amino]propanoate | C20H24N2O3 | 详情 | 详情 | |
| (VII) | 12132 | 2,5-Dimethoxytetrahydrofuran; 5-Methoxytetrahydro-2-furanyl methyl ether | 696-59-3 | C6H12O3 | 详情 | 详情 |
| (VIII) | 57378 | methyl (2R)-2-[(3,5-dimethylbenzoyl)(methyl)amino]-3-[4-(1H-pyrrol-1-yl)phenyl]propanoate | C24H26N2O3 | 详情 | 详情 | |
| (IX) | 57379 | (2R)-2-[(3,5-dimethylbenzoyl)(methyl)amino]-3-[4-(1H-pyrrol-1-yl)phenyl]propanoic acid | C23H24N2O3 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IX)1-Amino-1-cyclopropanecarboxylic acid (X) is protected as the N-Boc derivative (XI) employing Boc2O and NaOH in aqueous dioxane. Carbonyldiimidazole-mediated coupling of the Boc-aminoacid (XI) with butanesulfonamide (XII) produces the N-acyl sulfonamide (XIII). The N-Boc group of (XIII) is then cleaved under acidic conditions to give amine (XIV). This is finally coupled with acid (IX) in the presence of EDC and HOAt to furnish the corresponding amide.
| 【1】 Ksander, G.M.; Kukkola, P.J.; Robinson, L.A. (Novartis AG); N-aroylamino acid amides as endothelin inhibitors. EP 0821670; JP 1999505522; WO 9633170 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IX) | 57379 | (2R)-2-[(3,5-dimethylbenzoyl)(methyl)amino]-3-[4-(1H-pyrrol-1-yl)phenyl]propanoic acid | C23H24N2O3 | 详情 | 详情 | |
| (X) | 57382 | 1-Amino-1-cyclopropanecarboxylic acid; 1-Aminocyclopropane-1-carboxylic acid; 1-aminocyclopropane carboxylic acid; Carboxycyclopropylamine | 22059-21-8 | C4H7NO2 | 详情 | 详情 |
| (XI) | 57383 | Boc-1-aminocyclopropane-1-carboxylic acid; Boc-aminocyclopropanecarboxylic acid; Boc-L-alpha-aminocyclopropanecarboxylic acid | 88950-64-5 | C9H15NO4 | 详情 | 详情 |
| (XII) | 26780 | 1-butanesulfonamide | C4H11NO2S | 详情 | 详情 | |
| (XIII) | 57384 | tert-butyl 1-{[(butylsulfonyl)amino]carbonyl}cyclopropylcarbamate | C13H24N2O5S | 详情 | 详情 | |
| (XIV) | 57385 | N-[(1-aminocyclopropyl)carbonyl]-1-butanesulfonamide | C8H16N2O3S | 详情 | 详情 |