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【结 构 式】 
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【药物名称】Foropafant, SR-27417 【化学名称】2-[N-[2-(Dimethylamino)ethyl]-N-(3-pyridylmethyl)amino]-4-(2,4,6-triisopropylphenyl)thiazole 【CA登记号】136468-36-5 【 分 子 式 】C28H40N4S 【 分 子 量 】464.7218 |
【开发单位】Sanofi-synthélabo (Originator) 【药理作用】Antiallergy/Antiasthmatic Drugs, Asthma Therapy, GASTROINTESTINAL DRUGS, Irritable Bowel Syndrome, Agents for, RESPIRATORY DRUGS, Platelet-Activating Factor (PAF) Antagonists |
合成路线1
SR 27417 (N-(2-dimethylaminoethyl)-N-(3-pyridinylmethyl)[4-(2,4,6-triisopropylphenyl)thiazol-2-yl]amine difumarate) was prepared via a convergent route. Reductive amination of N,N-dimethylaminoethanamine (I) and pyridyl-3-carboxaldehyde (II) by sodium borohydride gave the amine (III). Eaction of pivaloyl chloride (IV) and potassium thiocyanate in anhydrous acetone provided the pivaloyl isothiocyanate (V), which was condensed in situ with the amine (III) to afford the protected thiourea (VI). Chlorhydric hydrolysis of (IV) gave the thiourea (VII) with the bromoketene (IX) in refluxing ethanol led to SR 27417.
| 【1】 Herbert, J.M.; Valette, G.; Bernat, A.; Savi, P.; Maffrand, J.P.; Le Fur, G.; SR 27417, a highly potent, selective and long-acting antagonist of the PAF receptor. Drugs Fut 1992, 17, 11, 1011. |
| 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) | 14881 | N-(2-aminoethyl)-N,N-dimethylamine; N(1),N(1)-dimethyl-1,2-ethanediamine; 2-Dimethylaminoethylamine | 108-00-9 | C4H12N2 | 详情 | 详情 |
| (II) | 12849 | Nicotinaldehyde; 3-Pyridinecarboxaldehyde | 500-22-1 | C6H5NO | 详情 | 详情 |
| (III) | 14883 | N-[2-(dimethylamino)ethyl]-N-(3-pyridinylmethyl)amine; N(1),N(1)-dimethyl-N(2)-(3-pyridinylmethyl)-1,2-ethanediamine | C10H17N3 | 详情 | 详情 | |
| (IV) | 13597 | 2,2-Dimethylpropanoyl chloride; Pivaloyl chloride | 3282-30-2 | C5H9ClO | 详情 | 详情 |
| (V) | 14885 | 2,2-dimethylpropanoyl isothiocyanate | C6H9NOS | 详情 | 详情 | |
| (VI) | 14886 | N-[2-(dimethylamino)ethyl]-N'-(2,2-dimethylpropanoyl)-N-(3-pyridinylmethyl)thiourea | C16H26N4OS | 详情 | 详情 | |
| (VII) | 14887 | N-[2-(dimethylamino)ethyl]-N-(3-pyridinylmethyl)thiourea | C11H18N4S | 详情 | 详情 | |
| (VIII) | 14888 | 1,3,5-triisopropylbenzene | 717-74-8 | C15H24 | 详情 | 详情 |
| (IX) | 14889 | 2-bromo-1-(2,4,6-triisopropylphenyl)-1-ethanone | C17H25BrO | 详情 | 详情 |