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【结 构 式】 
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【药物名称】Prazosin hydrochloride, CP-12299-1, Eurex, Hypovase, Minipress 【化学名称】1-(4-Amino-6,7-dimethoxyquinazolin-2-yl)-4-(2-furanylcarbonyl)piperazine hydrochloride 【CA登记号】19237-84-4, 19216-56-9 (free base) 【 分 子 式 】C19H22ClN5O4 【 分 子 量 】419.87129 |
【开发单位】Pfizer (Originator), Sanofi-synthélabo (Not Determined) 【药理作用】Benign Prostatic Hyperplasia Therapy, CARDIOVASCULAR DRUGS, Heart Failure Therapy, Hypertension, Treatment of, Peripheral Vascular Disease, Treatment of, Raynaud's Phenomenon, Treatment for , RENAL-UROLOGIC DRUGS, alpha1-Adrenoceptor Antagonists |
合成路线1
Treatment of carboxy polystyrene resin (I) with oxalyl chloride in dichloromethane, followed by reaction with Bu4NNCS in THF/DCM, affords isothiocyanate resin (II), to which 2-amino-4,5-dimethoxybenzonitrile (III) is attached by means of NMP to provide derivative (IV). Treatment of resin (IV) with 1-(2-furoyl)-piperazine (V) and EDC in chloroform in the presence of DIEA furnishes resin-bound guanidine (VI), from which prazosin is obtained as its trifluoroacetic acid salt (VII) by acidolysis with TFA/H2O at 80 C. Finally, the hydrochloride salt of prazosin can be obtained by treatment with HCl.
| 【1】 Wilson, L.J.; Traceless solid-phase synthesis of 2,4-diaminoquinazolines. Org Lett 2001, 3, 4, 585. |
| 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) | 10202 | Benzoic acid | 65-85-0 | C7H6O2 | 详情 | 详情 |
| (II) | 23530 | benzoyl isothiocyanate | 532-55-8 | C8H5NOS | 详情 | 详情 |
| (III) | 13038 | 2-Amino-4,5-dimethoxybenzonitrile | 26961-27-3 | C9H10N2O2 | 详情 | 详情 |
| (IV) | 52189 | N-benzoyl-N'-(2-cyano-4,5-dimethoxyphenyl)thiourea | C17H15N3O3S | 详情 | 详情 | |
| (V) | 30751 | 2-furyl(1-piperazinyl)methanone; 2-Furoyl-1-piperazine | 40172-95-0 | C9H12N2O2 | 详情 | 详情 |
| (VI) | 52190 | N-{[(2-cyano-4,5-dimethoxyphenyl)imino][4-(2-furoyl)-1-piperazinyl]methyl}benzamide | C26H25N5O5 | 详情 | 详情 | |
| (VII) | 52191 | [4-(4-amino-6,7-dimethoxy-2-quinazolinyl)-1-piperazinyl](2-furyl)methanone | C19H21N5O4 | 详情 | 详情 |