pentanoic acid -Drug Synthesis Database

【结构式】

【分子编号】19682

【品名】pentanoic acid

【CA登记号】109-52-4

【分子式】C₅H₁₀O₂

【分子量】102.1332

【元素组成】C 58.8% H 9.87% O 31.33%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(V)

Bromination of 6-aminopicoline (I) in aqueous H2SO4 gave bromopyridine (II), which was subsequently nitrated in cold H2SO4 to afford (III). Reduction of the nitro group of (III) with iron powder and HCl provided diamine (IV). The imidazopyridine system (VI) was then synthesized by condensation of (IV) with valeric acid (V) in polyphosphoric acid at 110 C. Alkylation of (VI) with the biphenylmethyl bromide (VII) in the presence of K2CO3 in DMF gave (VIII), which was coupled in turn with 2-(tri-n-butylstannyl)pyridine (IX) in the presence of Pd(PPh3)4 to produce the 6-(2-pyridinyl)-imidazopyridine derivative (X). Further oxidation of (X) with meta-chloroperbenzoic acid yielded the N-oxide (XI). Finally, deprotection of the tetrazole by treatment with methanolic HCl provided the target compound.

参考文献中间体

合成目标

【1】 Kim, N.J.; Seo, H.W.; Lee, S.H.; Shin, W.S.; Yi, K.Y.; Yoo, S.E.; Chan, O.J.; Jung, Y.S.; Lee, H.S.; Shin, Y.A.; Lee, B.H.; Kim, H.R.; Kim, S.J.; Suh, J.H. (Korea Research Institute of Chemical Technology); Pyridyl imidazole derivs. and processes for the preparation thereof. WO 9534564 .

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)	19678	6-methyl-2-pyridinamine; 6-methyl-2-pyridinylamine; 6-amino-2-picoline; 2-Amino-6-methylpyridine	1824-81-3	C₆H₈N₂	详情	详情
(II)	18337	5-bromo-6-methyl-2-pyridinamine; 5-bromo-6-methyl-2-pyridinylamine; 6-AMINO-3-BROMO-2-METHYLPYRIDINE	42753-71-9	C₆H₇BrN₂	详情	详情
(III)	19680	5-bromo-6-methyl-3-nitro-2-pyridinamine; 5-bromo-6-methyl-3-nitro-2-pyridinylamine		C₆H₆BrN₃O₂	详情	详情
(IV)	19681	2-amino-5-bromo-6-methyl-3-pyridinylamine; 5-bromo-6-methyl-2,3-pyridinediamine		C₆H₈BrN₃	详情	详情
(V)	19682	pentanoic acid	109-52-4	C₅H₁₀O₂	详情	详情
(VI)	19683	6-bromo-2-butyl-5-methyl-1H-imidazo[4,5-b]pyridine		C₁₁H₁₄BrN₃	详情	详情
(VII)	19684	1-[5-[4'-(bromomethyl)[1,1'-biphenyl]-2-yl]-1H-1,2,3,4-tetraazol-1-yl]ethyl ethyl ether; 5-[4'-(bromomethyl)[1,1'-biphenyl]-2-yl]-1-(1-ethoxyethyl)-1H-1,2,3,4-tetraazole		C₁₈H₁₉BrN₄O	详情	详情
(VIII)	19685	6-bromo-2-butyl-3-([2'-[1-(1-ethoxyethyl)-1H-1,2,3,4-tetraazol-5-yl][1,1'-biphenyl]-4-yl]methyl)-5-methyl-3H-imidazo[4,5-b]pyridine; 1-(5-[4'-[(6-bromo-2-butyl-5-methyl-3H-imidazo[4,5-b]pyridin-3-yl)methyl][1,1'-biphenyl]-2-yl]-1H-1,2,3,4-tetraazol-1-yl)ethyl ethyl ether		C₂₉H₃₂BrN₇O	详情	详情
(IX)	19686	(2-pyridyl)tributyltin;2-(tributylstannyl)pyridine;(2-Pyridinyl)tributylstannane;2-(1,1,1-Tributylstannyl)pyridine;2-(Tri-n-butylstannyl)pyridine;2-(Tributylstannyl)pyridine;2-(Tributyltin)pyridine;2-Pyridyltri-n-butyltin;2-Pyridyltributylstannane;2-Pyridyltributyltin;Tri-n-butyl(2-pyridyl)tin;Tri-n-butyl-2-pyridylstannane;Tributyl(pyridin-2-yl)stannane;Tributyl-2-pyridylstannane;Tributyl-2-pyridyltin	17997-47-6	C₁₇H₃₁NSn	详情	详情
(X)	19687	2-butyl-3-([2'-[1-(1-ethoxyethyl)-1H-1,2,3,4-tetraazol-5-yl][1,1'-biphenyl]-4-yl]methyl)-5-methyl-6-(2-pyridinyl)-3H-imidazo[4,5-b]pyridine; 1-[5-(4'-[[2-butyl-5-methyl-6-(2-pyridinyl)-3H-imidazo[4,5-b]pyridin-3-yl]methyl][1,1'-biphenyl]-2-yl)-1H-1,2,3,4-tetraazol-1-yl]ethyl ethyl ether		C₃₄H₃₆N₈O	详情	详情
(XI)	19688	2-[2-butyl-3-([2'-[1-(1-ethoxyethyl)-1H-1,2,3,4-tetraazol-5-yl][1,1'-biphenyl]-4-yl]methyl)-5-methyl-3H-imidazo[4,5-b]pyridin-6-yl]-1-pyridiniumolate		C₃₄H₃₆N₈O₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VI)

This compound can be obtained by several related ways: 1.- The cyclization of 3-aminothiophene-2-carboxamide (I) with pentanoyl anhydride (II) by means of DCC, DMAP and pyridine in DMF and NaOH gives 2-butylthieno[3,2-d]pyrimidin-4(3H)-one (III), which by reaction with POCl3 or SOCl2 affords 2-butyl-4-chlorothieno[3,2-d]pyrimidine (IV). Finally, this compound is condensed with cyclohexylamine (V) by means of triethylamine in in THF. 2.- The intermediate 2-butylthieno[3,2-d]pyrimidin-4-(3H)-one (III) can be obtained by other ways: a.- By cyclization of amide (I) with pentanoic acid (VI) by means of DCC, DMAP and pyridine in DMF and NaOH. b.- By cyclization of 3-aminothiophene-2-carboxylic acid methyl ester (VII) with pentanoic acid (VI) by means of DCC, DMAP and ammonia in dichloromethane. c.- By cyclization of 3-aminothiophene-2-carboxylic acid methyl ester (VII) with pentanoyl chloride (VIII) by means of pyridine and ammonia. d.- By cyclization of 3-aminothiophene-2-carboxylic acid (IX) with pentanoic anhydride (II) and ammonia.

参考文献中间体

合成目标

【1】 Crespo, M. I.; Pages, L.; Vega, A.; Segarra, V.; Lopez, M.; Domenech, T.; Miralpeix, M.; Beleta, J.; Ryder, H.; Palacios, J.M.; Design, synthesis, and biological activities of new thieno[3,2-d]pyrimidines as selective type 4 phosphodiesterase inhibitors. J Med Chem 1998, 41, 21, 4021.

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)	27682	3-amino-2-thiophenecarboxamide	147123-47-5	C₅H₆N₂OS	详情	详情
(II)	27683	pentanoic anhydride	2082-59-9	C₁₀H₁₈O₃	详情	详情
(III)	27684	2-butylthieno[3,2-d]pyrimidin-4(3H)-one		C₁₀H₁₂N₂OS	详情	详情
(IV)	27685	2-butyl-4-chlorothieno[3,2-d]pyrimidine		C₁₀H₁₁ClN₂S	详情	详情
(V)	17966	cyclohexanamine; cyclohexyl amine; cyclohexylamine	108-91-8	C₆H₁₃N	详情	详情
(VI)	19682	pentanoic acid	109-52-4	C₅H₁₀O₂	详情	详情
(VII)	27686	3-amino-2-thiophenecarboxylic acid methyl ester; methyl 3-amino-2-thiophenecarboxylate	22288-78-4	C₆H₇NO₂S	详情	详情
(VIII)	15116	pentanoyl chloride; valeryl chloride	638-29-9	C₅H₉ClO	详情	详情
(IX)	27687	3-amino-2-thiophenecarboxylic acid		C₅H₅NO₂S	详情	详情

Extended Information