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【结 构 式】

【分子编号】47603

【品名】(1S)-1,2,2-trimethylpropyl isocyanate; (3S)-3-isocyanato-2,2-dimethylbutane

【CA登记号】

【 分 子 式 】C7H13NO

【 分 子 量 】127.18636

【元素组成】C 66.11% H 10.3% N 11.01% O 12.58%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(VIII)

Esterification of urocanic acid (I) by means of HCl in MeOH affords methyl ester (II), which is then hydrogenated over Pd/C in MeOH to provide compound (III). Protection of the imidazole ring of (III) with triphenylmethyl chloride (trityl chloride) (IV) and Et3N in acetonitrile yields derivative (V), whose carboxylate moiety is reduced with LiAlH4 in refluxing THF to give alcohol (VI). Trityl removal from compound (VI) with HCl in refluxing EtOH furnishes hydrochloride (VII), which is finally converted into the desired product by condensation in refluxing acetonitrile with isocyanate (VIII) (which in turn can be obtained either by treatment of carboxylic acid (IX) with diphenyl phosphorazidate (DPPA) and Et3N in refluxing dioxane or by reaction of amine (X) with diphosgene (XI) and catalytic charcoal in refluxing ethyl acetate).

1 Stark, H.; et al.; [125I]Iodoproxyfan and related compounds: A reversible radioligand and novel classes of antagonists with high affinity and selectivity for the histamine H3 receptor. J Med Chem 1996, 39, 6, 1220.
2 Sasse, A.; Reidemeister, S.; Stark, H.; et al.; Novel partial agonists for the histamine H3 receptor with high in vitro and in vivo activity. J Med Chem 1999, 42, 20, 4269.
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) 27420 Urocanic acid; (E)-3-(1H-imidazol-4-yl)-2-propenoic acid 104-98-3 C6H6N2O2 详情 详情
(II) 39976 methyl (E)-3-(1H-imidazol-4-yl)-2-propenoate C7H8N2O2 详情 详情
(III) 39977 methyl 3-(1H-imidazol-4-yl)propanoate C7H10N2O2 详情 详情
(IV) 28630 Triphenylchloromethane; 1-[Chloro(diphenyl)methyl]benzene; Trityl chloride 76-83-5 C19H15Cl 详情 详情
(V) 47602 methyl 3-(1-trityl-1H-imidazol-4-yl)propanoate C26H24N2O2 详情 详情
(VI) 27424 3-(1-trityl-1H-imidazol-4-yl)-1-propanol C25H24N2O 详情 详情
(VII) 21245 3-(1H-imidazol-4-yl)-1-propanol C6H10N2O 详情 详情
(VIII) 47603 (1S)-1,2,2-trimethylpropyl isocyanate; (3S)-3-isocyanato-2,2-dimethylbutane C7H13NO 详情 详情
(IX) 47604 (2S)-2,3,3-trimethylbutyric acid C7H14O2 详情 详情
(X) 47605 (1S)-1,2,2-trimethylpropylamine; (2S)-3,3-dimethyl-2-butanamine 22526-47-2 C6H15N 详情 详情
(XI) 42918 Chloroformic acid trichloromethyl ester; di-Phosgene; Chloroformic Acid, Trichloromethyl Ester; Trichloromethyl chloroformate; Diphosgene 503-38-8 C2Cl4O2 详情 详情
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