N-[2-(benzyloxy)phenyl]acetamide -Drug Synthesis Database

【结构式】

【分子编号】56977

【品名】N-[2-(benzyloxy)phenyl]acetamide

【CA登记号】

【分子式】C₁₅H₁₅NO₂

【分子量】241.28964

【元素组成】C 74.67% H 6.27% N 5.8% O 13.26%

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：(II)

The reaction of 2-(benzyloxy)aniline (I) with acetic anhydride and pyridine gives the acetanilide (II), which is treated with P2S5 in hot toluene to yield the thioacetamide (III). The reaction of (III) with methyl iodide and K2CO3 in hot acetonitrile affords the methylated thioimidate (IV), which is cyclized with biphenyl-4-carbohydrazide (V) in hot DMF to provide 4-(2-benzyloxyphenyl)-3-(4-biphenylyl)-5-methyl-4H-1,2,4-triazole (VI). The hydrogenation of (VI) with H2 over Pd/C in methanol gives the corresponding phenol (VII), which is finally alkylated by means of 4-(2-chloroethyl)morpholine (VIII) and NaH in hot DMF to yield the target triazole. (1,2)

参考文献中间体

合成目标

【1】 Kakefuda, A.; Suzuki, T.; Tobe, T.; Tahara, A.; Sakamoto, S.; Tsukamoto, S.-I.; Discovery of 4,5-diphenyl-1,2,4-triazole derivatives as a novel class of selective antagonists for the human V1A receptor. Bioorg Med Chem 2002, 10, 6, 1905.
【2】 Suzuki, T.; Murakami, T.; Tobe, T.; Tahara, A. (Yamanouchi Pharmaceutical Co., Ltd.); Novel triazole derivs.. WO 0158880 .

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)	18065	2-(benzyloxy)aniline; 2-(benzyloxy)phenylamine		C₁₃H₁₃NO	详情	详情
(II)	56977	N-[2-(benzyloxy)phenyl]acetamide		C₁₅H₁₅NO₂	详情	详情
(III)	56978	N-[2-(benzyloxy)phenyl]ethanethioamide		C₁₅H₁₅NOS	详情	详情
(IV)	56979	methyl N-[2-(benzyloxy)phenyl]ethanimidothioate		C₁₆H₁₇NOS	详情	详情
(V)	56980	4-Biphenylcarboxylic acid hydrazide; 4-Phenylbenzhydrazide	18622-23-6	C₁₃H₁₂N₂O	详情	详情
(VI)	56981	benzyl 2-(3-[1,1'-biphenyl]-4-yl-5-methyl-4H-1,2,4-triazol-4-yl)phenyl ether; 4-[2-(benzyloxy)phenyl]-3-[1,1'-biphenyl]-4-yl-5-methyl-4H-1,2,4-triazole		C₂₈H₂₃N₃O	详情	详情
(VII)	56982	2-(3-[1,1'-biphenyl]-4-yl-5-methyl-4H-1,2,4-triazol-4-yl)phenol		C₂₁H₁₇N₃O	详情	详情
(VIII)	27355	4-(2-chloroethyl)morpholine	3647-69-6	C₆H₁₂ClNO	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

Acetylation of o-aminophenol (I) gives o-hydroxy acetanilide (II), which is then protected as the benzyl ether (III) with benzyl bromide and K2CO3. Treatment of acetamide (III) with P2S5 affords the corresponding thioamide (IV), and subsequent S-methylation of (IV) gives rise to the thioimidate (V). Cyclization of thioimidate (V) with 4-biphenylcarboxylic acid hydrazide (VI) in hot DMF leads to the triazole derivative (VII). After benzyl group hydrogenolysis in (VII), the resultant phenol (VIII) is alkylated with 1,6-dibromohexane (IX) to produce the bromohexyl ether (X). Finally, condensation of bromide (X) with N-methylpiperazine (XI) furnishes the title compound.

参考文献中间体

合成目标

【1】 Kakefuda, A.; et al.; Synthesis and pharmacological evaluation of 5-(4-biphenyl)-3-methyl-4-phenyl-1,2,4-triazole derivatives as a novel class of selective antagonists for the human vasopressin V1A receptor. J Med Chem 2002, 45, 12, 2589.

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)	18663	o-aminophenol; 2-aminophenol	95-55-6	C₆H₇NO	详情	详情
(II)	56976	2-Acetamidophenol; 2-Hydroxyacetanilide; o-Acetamidophenol; o-Hydroxyacetanilide	614-80-2	C₈H₉NO₂	详情	详情
(III)	56977	N-[2-(benzyloxy)phenyl]acetamide		C₁₅H₁₅NO₂	详情	详情
(IV)	56978	N-[2-(benzyloxy)phenyl]ethanethioamide		C₁₅H₁₅NOS	详情	详情
(V)	56979	methyl N-[2-(benzyloxy)phenyl]ethanimidothioate		C₁₆H₁₇NOS	详情	详情
(VI)	56980	4-Biphenylcarboxylic acid hydrazide; 4-Phenylbenzhydrazide	18622-23-6	C₁₃H₁₂N₂O	详情	详情
(VII)	56981	benzyl 2-(3-[1,1'-biphenyl]-4-yl-5-methyl-4H-1,2,4-triazol-4-yl)phenyl ether; 4-[2-(benzyloxy)phenyl]-3-[1,1'-biphenyl]-4-yl-5-methyl-4H-1,2,4-triazole		C₂₈H₂₃N₃O	详情	详情
(VIII)	56982	2-(3-[1,1'-biphenyl]-4-yl-5-methyl-4H-1,2,4-triazol-4-yl)phenol		C₂₁H₁₇N₃O	详情	详情
(IX)	24786	1,6-dibromohexane	629-03-8	C₆H₁₂Br₂	详情	详情
(X)	56983	3-[1,1'-biphenyl]-4-yl-4-{2-[(6-bromohexyl)oxy]phenyl}-5-methyl-4H-1,2,4-triazole; 2-(3-[1,1'-biphenyl]-4-yl-5-methyl-4H-1,2,4-triazol-4-yl)phenyl 6-bromohexyl ether		C₂₇H₂₈BrN₃O	详情	详情
(XI)	10061	1-Methylpiperazine; 1-Methyl piperazine; N-Methylpiperazine	109-01-3	C₅H₁₂N₂	详情	详情

Extended Information