2-(1-hydroxy-1lambda(5)-pyridin-4-yl)acetic acid -Drug Synthesis Database

【结构式】

【分子编号】17849

【品名】2-(1-hydroxy-1lambda(5)-pyridin-4-yl)acetic acid

【CA登记号】

【分子式】C₇H₉NO₃

【分子量】155.1534

【元素组成】C 54.19% H 5.85% N 9.03% O 30.94%

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：(XI)

Isomerization of (I) in refluxing trifluoromethanesulfonic acid provided the endocyclic olefin (II). Further reaction with ethyl chloroformate and triethylamine in toluene gave carbamate (III), which was then nitrated with a cooled mixture tetra-n-butylammonium nitrate and trifluoroacetic anhydride in dicloromethane, to afford a mixture of nitrocompounds (IV) and (V). After separation by column chromatography on silica gel, nitrocompound (V )was reduced with iron powder and calcium chloride in refluxing aqueous ethanol to amine (VII). Diazotization of amine (VII) with NaNO2 in 48% HBr in the presence of bromine at -5 C gave a mixture of monobromide (VIII) and dibromide (IX), which were separated on column chromatography. The dibromocarbamate (IX) was hydrolyzed in refluxing HCl to amine (X), which was finally coupled with 4-pyridylacetic acid N-oxide (XI) by treatment with EDC and HOBT.

参考文献中间体

合成目标

【1】 Njoroge, F.G.; et al.; Potent, selective, and orally bioavailable tricyclic pyridyl acetamide N-oxide inhibitors of farnesyl protein transferase with enhanced in vivo antitumor activity. J Med Chem 1998, 41, 10, 1561.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	17840	8-chloro-11-(4-piperidinylidene)-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine	C₁₉H₁₉ClN₂	详情	详情
(II)	17841	8-chloro-11-(4-piperidinyl)-11H-benzo[5,6]cyclohepta[1,2-b]pyridine	C₁₉H₁₉ClN₂	详情	详情
(III)	17842	ethyl 4-(8-chloro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl)-1-piperidinecarboxylate	C₂₂H₂₃ClN₂O₂	详情	详情
(IV)	17843	ethyl 4-(8-chloro-6-nitro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl)-1-piperidinecarboxylate	C₂₂H₂₂ClN₃O₄	详情	详情
(V)	17844	ethyl 4-(8-chloro-3-nitro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl)-1-piperidinecarboxylate	C₂₂H₂₂ClN₃O₄	详情	详情
(VII)	17845	ethyl 4-(3-amino-8-chloro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl)-1-piperidinecarboxylate	C₂₂H₂₄ClN₃O₂	详情	详情
(VIII)	17846	ethyl 4-(3-bromo-8-chloro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl)-1-piperidinecarboxylate	C₂₂H₂₂BrClN₂O₂	详情	详情
(IX)	17847	ethyl 4-(3,5-dibromo-8-chloro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl)-1-piperidinecarboxylate	C₂₂H₂₁Br₂ClN₂O₂	详情	详情
(X)	17848	3,5-dibromo-8-chloro-11-(4-piperidinyl)-11H-benzo[5,6]cyclohepta[1,2-b]pyridine	C₁₉H₁₇Br₂ClN₂	详情	详情
(XI)	17849	2-(1-hydroxy-1lambda(5)-pyridin-4-yl)acetic acid	C₇H₉NO₃	详情	详情

Extended Information