2-(2-cyclopentylethyl)-5-phenyl-1,3-oxazole -Drug Synthesis Database

【结构式】

【分子编号】26723

【品名】2-(2-cyclopentylethyl)-5-phenyl-1,3-oxazole

【CA登记号】

【分子式】C₁₆H₁₉NO

【分子量】241.333

【元素组成】C 79.63% H 7.94% N 5.8% O 6.63%

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：(XIV)

The intermediate sulfonyl chloride (VIII) has been obtained as follows: The reaction of phenacyl bromide (X) with sodium azide in hot DMF gives the azide (XI), which is condensed with 3-cyclopentylpropionyl chloride (XII) by means of LDA yielding the enol ester (XIII). The cyclization of (XIII) by means of triethyl phosphite in refluxing hexane affords 2-(2-cyclopentylethyl)-5-phenyloxazole (XIV), which is finally sulfonated with chlorosulfonic acid to afford the target sulfonyl chloride (VIII).

参考文献中间体

合成目标

【1】 Ok, H.O.; Candelore, M.R.; Reigle, L.B.; et al.; Substituted oxazole benzenesulfonamides as potent human beta3 adrenergic receptor agonists. 217th ACS Natl Meet (March 21 1999, Anaheim) 1999, Abst MEDI 114.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VIII)	26718	4-[2-(2-cyclopentylethyl)-1,3-oxazol-5-yl]benzenesulfonyl chloride		C₁₆H₁₈ClNO₃S	详情	详情
(X)	10315	2-Bromo-1-phenyl-ethanone; 2-Bromo-1-phenyl-1-ethanone	70-11-1	C₈H₇BrO	详情	详情
(XI)	26720	2-azido-1-phenyl-1-ethanone		C₈H₇N₃O	详情	详情
(XII)	26721	3-cyclopentylpropanoyl chloride	104-97-2	C₈H₁₃ClO	详情	详情
(XIII)	26722	(Z)-2-azido-1-phenylethenyl 3-cyclopentylpropanoate		C₁₆H₁₉N₃O₂	详情	详情
(XIV)	26723	2-(2-cyclopentylethyl)-5-phenyl-1,3-oxazole		C₁₆H₁₉NO	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VII)

The cyclization of phenacyl bromide (I) with acetamide (II) by heating at 130 C gives 2-methyl-5-phenyloxazole (III), which is brominated with NBS in CCl4 to yield the dibromo derivative (IV). The condensation of (IV) with cyclopentylmethylmagnesium bromide (V) by means of Li2CuCl4 affords 4-bromo-2-(2-cyclopentylethyl)-5-phenyloxazole (VI), which is debrominated by hydrogenation with H2 over Pd(OH)2 in methanol, providing 2-(2-cyclopentylethyl)-5-phenyloxazole (VII). The sulfonation of the phenyl ring of (VII) with chlorosulfonic acid gives the sulfonyl chloride (VIII), which is condensed with the aniline derivative (IX) by means of pyridine in dichloromethane to yield the sulfonamide (X). Finally, elimination of the Boc protecting group of (X) by means of HCl in methanol affords the target compound.

参考文献中间体

合成目标

【1】 Candelore, M.R.; Ok, H.O.; Reigle, L.B.; et al.; Substituted oxazole benzenesulfonamides as potent human beta3-adrenergic receptor agonist. Bioorg Med Chem Lett 2000, 10, 14, 1531.

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)	10315	2-Bromo-1-phenyl-ethanone; 2-Bromo-1-phenyl-1-ethanone	70-11-1	C₈H₇BrO	详情	详情
(II)	50352	Acetamide; Acetic acid amide; Ethanamide	60-35-5	C₂H₅NO	详情	详情
(III)	50348	2-methyl-5-phenyl-1,3-oxazole		C₁₀H₉NO	详情	详情
(IV)	50349	4-bromo-2-(bromomethyl)-5-phenyl-1,3-oxazole		C₁₀H₇Br₂NO	详情	详情
(V)	50350	bromo(cyclopentylmethyl)magnesium		C₆H₁₁BrMg	详情	详情
(VI)	50351	4-bromo-2-(2-cyclopentylethyl)-5-phenyl-1,3-oxazole		C₁₆H₁₈BrNO	详情	详情
(VII)	26723	2-(2-cyclopentylethyl)-5-phenyl-1,3-oxazole		C₁₆H₁₉NO	详情	详情
(VIII)	26718	4-[2-(2-cyclopentylethyl)-1,3-oxazol-5-yl]benzenesulfonyl chloride		C₁₆H₁₈ClNO₃S	详情	详情
(IX)	26553	tert-butyl 4-aminophenethyl[(2R)-2-hydroxy-2-(3-pyridinyl)ethyl]carbamate		C₂₀H₂₇N₃O₃	详情	详情
(X)	26718	4-[2-(2-cyclopentylethyl)-1,3-oxazol-5-yl]benzenesulfonyl chloride		C₁₆H₁₈ClNO₃S	详情	详情

Extended Information