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【结 构 式】

【分子编号】65550

【品名】 

【CA登记号】 

【 分 子 式 】C12H24N2O

【 分 子 量 】212.33544

【元素组成】C 67.88% H 11.39% N 13.19% O 7.53%

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:(V)

Ibodutant is synthesized (1) starting from commercially available methyl tetrahydro-2H-pyran-4-carboxylate (I), which is hydrolyzed to the corresponding carboxylic acid by treatment with sodium hydroxide (1 M) and immediately transformed to the acyl chloride (II) with oxalyl chloride and catalytic DMF in dichloromethane. Reaction of (II) with isonipecotamide (III) in DMF/dichloromethane in the presence of triethylamine gives the diamide (IV), which is successfully reduced to the corresponding diamine (V) using lithium aluminum hydride in refluxing THF. Coupling of (V) with tert-butyloxycarbonyl-(R )-phenylalanine N-hydroxysuccinimide ester (Boc-D-Phe-OSu) in THF and Boc deprotection with HCl/dioxane gives (VI). Further coupling of (VI) with the N-Boc derivative of aminocyclopentanecarboxylic acid (VII) in the presence of EDC.HCl and HOBT, and deprotection of the Boc group with HCl/dioxane, provides 1-aminocyclopentanecarboxylic acid [2-phenyl-1-(R)-[[1-(tetrahydropyran-4-ylmethyl)piperidin-4-ylmethyl]carbamoyl]ethyl]amide (VIII). The free amine compound (VIII) is in turn coupled with 6-methylbenzo[b]thiophene-2-carbonyl chloride (IX), obtained from the corresponding carboxylic acid by reaction with oxalyl chloride under the usual conditions, finally giving ibodutant. Scheme 1.

1 Fedi, V., Altamura, M., Catalioto, R.M. et al. Discovery of a series of potent and selective linear tachykinin NK2 receptor antagonists. J Med Chem 2007, 50(20): 4793-807.
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) 65548 Methyl tetrahydropyran-4-carboxylate; Tetrahydropyran-4-carboxylic acid methyl ester; THPE 110238-91-0 C7H12O3 详情 详情
(II) 50860 tetrahydro-2H-pyran-4-carbonyl chloride 40191-32-0 C6H9ClO2 详情 详情
(III) 11762 4-Piperidinecarboxamide; Isonipecotamide 39546-32-2 C6H12N2O 详情 详情
(IV) 65549     C12H20N2O3 详情 详情
(V) 65550     C12H24N2O 详情 详情
(VI) 65551     C21H33N3O2 详情 详情
(VII) 33149 1-aminocyclopentanecarboxylic acid 52-52-8 C6H11NO2 详情 详情
(VIII) 65552     C27H42N4O3 详情 详情
(IX) 65553 6-Methyl-1-Benzothiophene-2-Carbonyl Chloride; 6-Methyl-Benzo[B]Thiophene-2-Carbonyl Chloride   C10H7ClOS 详情 详情
Extended Information