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【结 构 式】 
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【药物名称】Tulopafant, RP-59227, 59227-RP 【化学名称】(R)-(+)-N-(3-Benzoylphenyl)-3-(3-pyridyl)-1H,3H-pyrrolo[1,2-c]thiazole-7-carboxamide 【CA登记号】116289-53-3 【 分 子 式 】C25H19N3O2S 【 分 子 量 】425.51308 |
【开发单位】Aventis Pharma (Originator) 【药理作用】Angina pectoris, Treatment of, Antiarrhythmic Drugs, CARDIOVASCULAR DRUGS, Treatment of Disorders of the Coronary Arteries and Atherosclerosis, Platelet-Activating Factor (PAF) Antagonists |
合成路线1
The cyclization of pyridine-3-carbaldehyde (II) with L-cysteine (I) in ethanol gives the thiazolidine derivative (III), which is treated with formic acid, yielding a diastereomeric mixture of formyl derivatives from which the desired (2R,4R)-(IV) is isolated by crystallization. The cyclization of (2R,4R)-(IV) with ethyl 2,3-dichloropropionate (V) by means of TsCl and Et3N affords (2R)-(3-pyridyl)-1H,3H-pyrrolo[1,2-c]thiazole-7-carboxylic acid ethyl ester (VI), which is hydrolyzed with NaOH to the corresponding free acid (VII). Finally, this compound is condensed with 3-aminobenzophenone (VIII) by means of SOCl2 to provide the target amide.
| 【1】 (Aventis SA); 1H,3H-pyrrolo[1,2-c]thiazole derivs.. EP 0253711; FR 2601015; JP 1988022589 . |
| 【2】 Rajoharison, H.G. (Aventis Pharma SA); Process for the preparation of dextrorotatory 3-(3-pyridyl)-1H,3H-pyrrolo[1,2-c]-7-thiazolecarboxylic acid. EP 0297987; US 4906757 . |
| 【3】 Lavé, D.; James, C.; Rajoharison, H.; Bost, P.E.; Cavero, I.; PYRROLO[1,2-c]THIAZOLE DERIVATIVES: POTENT PAF RECEPTOR ANTAGONISTS. Drugs Fut 1989, 14, 9, 891. |
| 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) | 14643 | L-cysteine; (R)-2-Amino-3-mercaptopropionic acid | 52-90-4 | C3H7NO2S | 详情 | 详情 |
| (II) | 12849 | Nicotinaldehyde; 3-Pyridinecarboxaldehyde | 500-22-1 | C6H5NO | 详情 | 详情 |
| (III) | 38634 | (4R)-2-(3-pyridinyl)-1,3-thiazolidine-4-carboxylic acid | C9H10N2O2S | 详情 | 详情 | |
| (IV) | 43713 | (2R,4R)-3-formyl-2-(3-pyridinyl)-1,3-thiazolidine-4-carboxylic acid | C10H10N2O3S | 详情 | 详情 | |
| (V) | 43714 | ethyl 2,3-dichloropropanoate | 6628-21-3 | C5H8Cl2O2 | 详情 | 详情 |
| (VI) | 43715 | ethyl (3R)-3-(3-pyridinyl)-1H-pyrrolo[1,2-c][1,3]thiazole-7-carboxylate | C14H14N2O2S | 详情 | 详情 | |
| (VII) | 43716 | (3R)-3-(3-pyridinyl)-1H-pyrrolo[1,2-c][1,3]thiazole-7-carboxylic acid | C12H10N2O2S | 详情 | 详情 | |
| (VIII) | 39112 | 3-Aminobenzophenone; (3-aminophenyl)(phenyl)methanone | 2835-78-1 | C13H11NO | 详情 | 详情 |