N(1)-[(1R)-4-azido-1-[(1R,2S,6R,8R)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.0(2,6)]dec-4-yl]butyl]-N(1)-phenethyl-1,1-cyclopentanedicarboxamide -Drug Synthesis Database

【结构式】

【分子编号】35563

【品名】N(1)-[(1R)-4-azido-1-[(1R,2S,6R,8R)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.0(2,6)]dec-4-yl]butyl]-N(1)-phenethyl-1,1-cyclopentanedicarboxamide

【CA登记号】

【分子式】C₂₉H₄₂BN₅O₄

【分子量】535.49478

【元素组成】C 65.05% H 7.91% B 2.02% N 13.08% O 11.95%

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：(XV)

Carbethoxylation of cyclopentanecarboxylic acid (VIII) with ethyl chloroformate and LDA afforded monoethyl cyclopentane-1,1-dicarboxylate (IX), which was coupled with phenethylamine (X) in the presence of TBTU, yielding amide (XI). Subsequent saponification of the ethyl ester group of (XI) gave carboxylic acid (XII), which was activated as the mixed anhydride (XIII) with isobutyl chloroformate and triethylamine. Coupling of this anhydride with aminoboronate (VII) produced the bisamide (XIV). After displacement of the bromine of (XIV) with NaN3, the resulting azide (XV) was reduced to amine (XVI) by hydrogenation over Pd/C. The required guanidine (XVII) was then obtained by condensation of (XVI) with cyanamide in refluxing EtOH. Finally, cleavage of the boronate ester by exchange with phenylboronic acid in the presence of benzenesulfonic acid furnished the title compound.

参考文献中间体

合成目标

【1】 Verbeuren, T.; Rupin, A.; De Nanteuil, G.; Gloanec, P.; New dicarbonyl cycloalkyl based thrombin inhibitors with improved activity and selectivity compared to (D)-Phe-Pro-boroArg derivatives . 218th ACS Natl Meet (Aug 22 1999, New Orleans) 1999, Abst MEDI 201.
【2】 Gloanec, P.; Portevin, B.; Lila, C.; Rupin, A.; de Nanteuil, G.; Simonet, S.; Verbeuren, T. (ADIR et Cie.); Cpds. derived from boronic acid. EP 0792883; FR 2745288; US 5814622 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VI)	35561	(1R)-4-bromo-1-[(1R,2S,6R,8R)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.0(2,6)]dec-4-yl]-1-butanamine; (1R)-4-bromo-1-[(1R,2S,6R,8R)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.0(2,6)]dec-4-yl]butylamine		C₁₄H₂₅BBrNO₂	详情	详情
(VIII)	20734	cyclopentanecarboxylic acid	3400-45-1	C₆H₁₀O₂	详情	详情
(IX)	32539	1-(ethoxycarbonyl)cyclopentanecarboxylic acid		C₉H₁₄O₄	详情	详情
(X)	18333	Phenethylamine; 2-Phenyl-1-ethanamine	64-04-0	C₈H₁₁N	详情	详情
(XI)	32540	ethyl 1-[(phenethylamino)carbonyl]cyclopentanecarboxylate		C₁₇H₂₃NO₃	详情	详情
(XII)	32541	1-[(phenethylamino)carbonyl]cyclopentanecarboxylic acid		C₁₅H₁₉NO₃	详情	详情
(XIII)	32542	1-[N-(2-Phenylethyl)carbamoyl]cyclopentylcarbonyl isobutoxycarbonyl anhydride		C₂₀H₂₇NO₅	详情	详情
(XIV)	35562	N(1)-[(1R)-4-bromo-1-[(1R,2S,6R,8R)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.0(2,6)]dec-4-yl]butyl]-N(1)-phenethyl-1,1-cyclopentanedicarboxamide		C₂₉H₄₂BBrN₂O₄	详情	详情
(XV)	35563	N(1)-[(1R)-4-azido-1-[(1R,2S,6R,8R)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.0(2,6)]dec-4-yl]butyl]-N(1)-phenethyl-1,1-cyclopentanedicarboxamide		C₂₉H₄₂BN₅O₄	详情	详情
(XVI)	35564	N(1)-[(1R)-4-amino-1-[(1R,2S,6R,8R)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.0(2,6)]dec-4-yl]butyl]-N(1)-phenethyl-1,1-cyclopentanedicarboxamide		C₂₉H₄₄BN₃O₄	详情	详情
(XVII)	35565	N(1)-[(1R)-4-[[amino(imino)methyl]amino]-1-[(1R,2S,6R,8R)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.0(2,6)]dec-4-yl]butyl]-N(1)-phenethyl-1,1-cyclopentanedicarboxamide		C₃₀H₄₆BN₅O₄	详情	详情

Extended Information