3-cyclopentyl-1-propanol -Drug Synthesis Database

【结构式】

【分子编号】27752

【品名】3-cyclopentyl-1-propanol

【CA登记号】767-05-5

【分子式】C₈H₁₆O

【分子量】128.21444

【元素组成】C 74.94% H 12.58% O 12.48%

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：(XV)

Cyclopentylpropanol (XV) was converted to mesylate (XVI) and subsequently treated with NaI to give iodide (XVII). Then, alkylation of phenyltetrazolone (XIX), (obtained from phenyl isocyanate (XVIII) and aluminum azide), with iodide (XVII) afforded the substituted tetrazolone (XX). Nitration of the phenyl ring of (XX) employing nitronium tetrafluoborate produced the 4-nitro derivative (XXI) along with minor amounts of the 2-nitro isomer, which was separated by flash chromatography. After catalytic hydrogenation of the nitro group of (XXI) to aniline (XXII), diazotization, followed by treatment with an AcOH solution of SO2 in the presence of CuCl furnished sulfonyl chloride (XXIII). Coupling of this sulfonyl chloride with the intermediate amine (VII) in the presence of pyridine gave sulfonamide (XXIV). Finally, the Boc protecting group of (XXIV) was removed by acidic treatment to provide the title compound.

参考文献中间体

合成目标

【1】 Shih, T.L.; Candelore, M.R.; Cascieri, M.A.; L-770,644: A potent and selective human beta3 adrenergic receptor agonist with improved oral bioavailability. Bioorg Med Chem Lett 1999, 9, 9, 1251.
【2】 Fisher, M.H.; Naylor, E.M.; Ok, D.; Weber, A.E.; Shih, T.; Ok, H. (Merck & Co., Inc.); Substd. sulfonamides as selective beta3 agonists for the treatment of diabetes and obesity. EP 0757674; JP 1997512275; US 5541197; US 5561142; WO 9529159 .
【3】 Smith, R.G. (Merck & Co., Inc.); Combination therapy for the treatment of diabetes and obesity. JP 1999515027; WO 9716189 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VII)	26553	tert-butyl 4-aminophenethyl[(2R)-2-hydroxy-2-(3-pyridinyl)ethyl]carbamate		C₂₀H₂₇N₃O₃	详情	详情
(XV)	27752	3-cyclopentyl-1-propanol	767-05-5	C₈H₁₆O	详情	详情
(XVI)	27753	3-cyclopentylpropyl methanesulfonate		C₉H₁₈O₃S	详情	详情
(XVII)	27754	1-(3-iodopropyl)cyclopentane		C₈H₁₅I	详情	详情
(XVIII)	11289	1-Isocyanatobenzene; phenyl isocyanate; Phenylisocyanate	103-71-9	C₇H₅NO	详情	详情
(XIX)	27755	1-phenyl-1,4-dihydro-5H-1,2,3,4-tetraazol-5-one		C₇H₆N₄O	详情	详情
(XX)	27756	1-(3-cyclopentylpropyl)-4-phenyl-1,4-dihydro-5H-1,2,3,4-tetraazol-5-one		C₁₅H₂₀N₄O	详情	详情
(XXI)	27757	1-(3-cyclopentylpropyl)-4-(4-nitrophenyl)-1,4-dihydro-5H-1,2,3,4-tetraazol-5-one		C₁₅H₁₉N₅O₃	详情	详情
(XXII)	27758	1-(4-aminophenyl)-4-(3-cyclopentylpropyl)-1,4-dihydro-5H-1,2,3,4-tetraazol-5-one		C₁₅H₂₁N₅O	详情	详情
(XXIII)	27759	4-[4-(3-cyclopentylpropyl)-5-oxo-4,5-dihydro-1H-1,2,3,4-tetraazol-1-yl]benzenesulfonyl chloride		C₁₅H₁₉ClN₄O₃S	详情	详情
(XXIV)	27760	tert-butyl 4-[([4-[4-(3-cyclopentylpropyl)-5-oxo-4,5-dihydro-1H-1,2,3,4-tetraazol-1-yl]phenyl]sulfonyl)amino]phenethyl[(2R)-2-hydroxy-2-(3-pyridinyl)ethyl]carbamate		C₃₅H₄₅N₇O₆S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XV)

A further procedure for the synthesis of the intermediate sulfonyl chloride (XXIII) has been reported. Cyclopentylpropanol (XV) was prepared by borane reduction of carboxylic acid (XXV). Subsequent conversion of (XV) to mesylate (XVI), followed by displacement with NaN3 provided azide (XXVI). Then, cycloaddition of isocyanate (XXVIII), (obtained by treatment of sulfanilic acid (XXVII) with phosgene in boiling o-dichlorobenzene), to azide (XXVI) generated the required tetrazolone (XXIII).

参考文献中间体

合成目标

【1】 Ho, G.J. (Merck & Co., Inc.); Process for the preparation of a beta3-agonist. WO 9734880 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XV)	27752	3-cyclopentyl-1-propanol	767-05-5	C₈H₁₆O	详情	详情
(XVI)	27753	3-cyclopentylpropyl methanesulfonate		C₉H₁₈O₃S	详情	详情
(XXIII)	27759	4-[4-(3-cyclopentylpropyl)-5-oxo-4,5-dihydro-1H-1,2,3,4-tetraazol-1-yl]benzenesulfonyl chloride		C₁₅H₁₉ClN₄O₃S	详情	详情
(XXV)	27761	3-cyclopentylpropionic acid	140-77-2	C₈H₁₄O₂	详情	详情
(XXVI)	27762	1-(3-azidopropyl)cyclopentane		C₈H₁₅N₃	详情	详情
(XXVII)	27763	4-aminobenzenesulfonic acid	121-57-3	C₆H₇NO₃S	详情	详情
(XXVIII)	27764	4-isocyanatobenzenesulfonyl chloride		C₇H₄ClNO₃S	详情	详情

Extended Information