2-(2-Methoxyphenyl)-4,4-dimethyl-2-oxazoline; 2-(2-Methoxyphenyl)-4,4-dimethyl-4,5-dihydro-1,3-oxazole; 2-(4,4-Dimethyl-4,5-dihydro-1,3-oxazol-2-yl)phenyl methyl ether -Drug Synthesis Database

【结构式】

【分子编号】13927

【品名】2-(2-Methoxyphenyl)-4,4-dimethyl-2-oxazoline; 2-(2-Methoxyphenyl)-4,4-dimethyl-4,5-dihydro-1,3-oxazole; 2-(4,4-Dimethyl-4,5-dihydro-1,3-oxazol-2-yl)phenyl methyl ether

【CA登记号】57598-33-1

【分子式】C₁₂H₁₅NO₂

【分子量】205.25664

【元素组成】C 70.22% H 7.37% N 6.82% O 15.59%

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：(VII)

The synthesis of the biphenyl tail involves first the conversion of 2-methoxybenzoic acid (VI) into oxazoline (VII), followed by displacement of the methoxy group by 4-tolylmagnesium bromide to yield biphenyloxazoline (VIII). Oxazoline (VIII) may be converted into biphenylnitrile (IX) by reaction with phosphorous oxychloride in pyridine. Reaction of biphenylnitrile (VIII) with tri-n-butyltin azide in refluxing xylenes, followed by destannylation and protection with a triphenylmethyl group, yields triphenylmethyl-protected biphenyltetrazole (X). Benzylic bromination yields the completed tail (XI)

参考文献中间体

合成目标

【1】 Duncia, J.V.; Carini, D.J.; Chiu, A.T.; Pierce, M.E.; Price, W.A.; Smith, R.D.; Wells, G.J.; Wong, P.C.; Wexler, R.R.; Johnson, A.L.; Timmermans, P.B.M.W.M.; DuP 753. Drugs Fut 1991, 16, 4, 305.
【2】 Carini, D.J.; Duncia, J.V.; Aldrich, P.E.; Chiu, A.T.; Johnson, A.L.; Pierce, M.E.; Santella, J.B.; Wells, G.J.; Wexler, R.R.; Wong, P.C.; Timmermans, P.B.M.W.M.; Nonpeptide angiotensin II receptor antagonists: The discovery of a series of N-(biphenylmethyl)imidazoles as potent, orally-active antihypertensives. J Med Chem 1991, 34, 8, 2225-47.

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)	13926	2-Methoxybenzoic acid; o-Methoxybenzoic Acid	579-75-9	C₈H₈O₃	详情	详情
(VII)	13927	2-(2-Methoxyphenyl)-4,4-dimethyl-2-oxazoline; 2-(2-Methoxyphenyl)-4,4-dimethyl-4,5-dihydro-1,3-oxazole; 2-(4,4-Dimethyl-4,5-dihydro-1,3-oxazol-2-yl)phenyl methyl ether	57598-33-1	C₁₂H₁₅NO₂	详情	详情
(VIII)	13928	4,4-Dimethyl-2-(4'-methyl-2-biphenyllyl)2-oxazoline; 4,4-Dimethyl-2-(4'-methyl[1,1'-biphenyl]-2-yl)-4,5-dihydro-1,3-oxazole	84392-32-5	C₁₈H₁₉NO	详情	详情
(IX)	13929	2-Cyano-4'-methylbiphenyl; 4'-Methyl[1,1'-biphenyl]-2-carbonitrile	114772-53-1	C₁₄H₁₁N	详情	详情
(X)	13930	5-(4'-Methyl[1,1'-biphenyl]-2-yl)-1-trityl-1H-1,2,3,4-tetraazole		C₃₃H₂₆N₄	详情	详情
(XI)	13931	5-(4'-Bromo[1,1'-biphenyl]-2-yl)-1-trityl-1H-1,2,3,4-tetraazole		C₃₂H₂₃BrN₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

2-Methoxybenzoic acid (I) was protected as the oxazoline (II). Further coupling with tolylmagnesium bromide, followed by acid hydrolysis of the oxazoline provided the intermediate biphenyl carboxylic acid (III).

参考文献中间体

合成目标

【1】 Hosogai, N.; Tanaka, H.; Tomita, M.; Ohkawa, T.; Hemmi, K.; Setoi, H.; Zenkoh, O.; Synthesis and characterization of orally active nonpeptide vasopressin V2 receptor antagonists. Chem Pharm Bull 1999, 47, 4, 501.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	35657	bromo(4-methylphenyl)magnesium	4294-57-9	C₇H₇BrMg	详情	详情
(I)	13926	2-Methoxybenzoic acid; o-Methoxybenzoic Acid	579-75-9	C₈H₈O₃	详情	详情
(II)	13927	2-(2-Methoxyphenyl)-4,4-dimethyl-2-oxazoline; 2-(2-Methoxyphenyl)-4,4-dimethyl-4,5-dihydro-1,3-oxazole; 2-(4,4-Dimethyl-4,5-dihydro-1,3-oxazol-2-yl)phenyl methyl ether	57598-33-1	C₁₂H₁₅NO₂	详情	详情
(III)	16915	4'-methyl[1,1'-biphenyl]-2-carboxylic acid	7148-03-0	C₁₄H₁₂O₂	详情	详情

Extended Information