m-Chloroperbenzoic acid; 3-Chlorobenzenecarboperoxoic acid -Drug Synthesis Database

【结构式】

【分子编号】17888

【品名】m-Chloroperbenzoic acid; 3-Chlorobenzenecarboperoxoic acid

【CA登记号】937-14-4

【分子式】C₇H₅ClO₃

【分子量】172.5676

【元素组成】C 48.72% H 2.92% Cl 20.54% O 27.81%

与该中间体有关的原料药合成路线共 4 条

合成路线1 合成路线2 合成路线3 合成路线4

合成路线1

该中间体在本合成路线中的序号：

The condensation of 2,3-dimethyl-4-nitropyridine N-oxide (I) with 2,2,2-trifluoroethanol (II) by means of K2CO3 in hot HMPT gives 2,3-dimethyl-4-(2,2,2-trifluoroethoxy)pyridine N-oxide (III), which by isomerization in acetic anhydride at 100 C is converted to 2-(hydroxymethyl)-3-methyl-4-(2,2,2-trifluoroethoxy)pyridine (IV). The reaction of (IV) with SOCl2 in refluxing CHCl3 affords the corresponding chloromethyl derivative (V), which is condensed with 2-mercaptobenzimidazole (VI) by means of sodium methoxide in refluxing methanol to yield 2-(2-benzimidazolylthiomethyl)-3-methyl-4-(2,2,2-trifluoroethoxy)pyridin (VII). Finally, this compound is oxidized with m-chloroperbenzoic acid in CHCl3.

参考文献中间体

合成目标

【1】 Makino, T.; Tabata, T.; Hirai, S.; Stabilized pharmaceutical composition comprising a benzimidazole compound, its production and its use as an antiulcer agent.. EP 237200; JP 87277322 .
【2】 Nohara, A.; Maki, Y. (Takeda Chemical Industries, Ltd.); Pyridine derivs. and their production. AU 8545895; EP 0174726; ES 8607288; JP 1986050978; US 4628098; US 4689333 .
【3】 Prous, J.; Castaner, J.; LANSOPRAZOLE < Prop INN >. Drugs Fut 1989, 14, 7, 625.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	17888	m-Chloroperbenzoic acid; 3-Chlorobenzenecarboperoxoic acid	937-14-4	C₇H₅ClO₃	详情	详情
(I)	19482	2,3-dimethyl-4-nitro-1-pyridiniumolate	37699-43-7	C₇H₈N₂O₃	详情	详情
(II)	19483	2,2,2-trifluoro-1-ethanol	75-89-8	C₂H₃F₃O	详情	详情
(III)	19484	2,3-dimethyl-4-(2,2,2-trifluoroethoxy)-1-pyridiniumolate		C₉H₁₀F₃NO₂	详情	详情
(IV)	19485	[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridinyl]methanol		C₉H₁₀F₃NO₂	详情	详情
(V)	19486	2-(chloromethyl)-3-methyl-4-(2,2,2-trifluoroethoxy)pyridine; 2-(chloromethyl)-3-methyl-4-pyridinyl 2,2,2-trifluoroethyl ether	127337-60-4	C₉H₉ClF₃NO	详情	详情
(VI)	12821	2-Mercaptobenzinidiazole; 1H-Benzimidazol-2-ylhydrosulfide; 1H-Benzimidazole-2-thiol; 2-Benzimidazolethiol; o-Phenylenethiourea; 2-Benzimidazolinethione; 1,3-Dihydro-2H-benzimidazole-2-thione	583-39-1	C₇H₆N₂S	详情	详情
(VII)	19488	2-[(1H-benzimidazol-2-ylsulfanyl)methyl]-3-methyl-4-pyridinyl 2,2,2-trifluoroethyl ether; 2-([[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridinyl]methyl]sulfanyl)-1H-benzimidazole	103577-40-8	C₁₆H₁₄F₃N₃OS	详情	详情

合成路线2

该中间体在本合成路线中的序号：

The condensation of 4-chloro-2,3-dimethylpyridine N-oxide (I) with 3-methoxypropanol (II) by means of NaH in DMSO gives 4-(3-methoxypropoxy)-2,3-dimethylpyridine N-oxide (III), which is treated with acetic anhydride at 90 C yielding 2-(acetoxymethyl)-4-(3-methoxypropoxy)-3-methylpyridine (IV). The hydrolysis of (IV) with NaOH in ethanol affords 2-(hydroxymethyl)-4-(3-methoxypropoxy)-3-methylpyridine (V), which by treatment with SOCl2 in dichloromethane is converted into 2-(chloromethyl)-4-(3-methoxypropoxy)-3-methylpyridine (VI). The condensation of (VI) with 2-mercaptobenzimidazole (VII) by means of NaOH in ethanol gives 2-[4-(3-methoxypropoxy)-3-methylpyridin-2-ylmethylthio]benzimidazole (VIII), which is oxidized with m-chloroperbenzoic acid in ether - dichloromethane to afford 2-[4-(3-methoxypropoxy)-3-methylpyridin-2-ylsulfinyl]benzimidazole (IX). Finally, this compound is treated wtih aqueous Na2CO3.

参考文献中间体

合成目标

【1】 Souda, S.; Ueda, N.; Miyazawa, S.; Tagami, K.; Nomoto, S.; Okita, M.; Shimomura, N.; Kaneko, T.; Fujimoto, M.; Murakami, M.; Oketani, K.; Fujisaki, H.; Shibata, H.; Wakabayashi, T. (Eisai Co., Ltd.); Pyridine derivs., pharmaceutical compsns. comprising the same, the use of the same for the manufacture of medicaments having therapeutic or preventative value, and a process for preparing the same. AU 8781138; EP 0268956; EP 0475456; EP 0654471; EP 0786461; JP 1989006270; JP 1993247035; JP 1995291967; US 5045552; US 5998445 .
【2】 Castaner, J.; Prous, J.; E-3810. Drugs Fut 1991, 16, 1, 19.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	17888	m-Chloroperbenzoic acid; 3-Chlorobenzenecarboperoxoic acid	937-14-4	C₇H₅ClO₃	详情	详情
(I)	12815	4-chloro-2,3-dimethyl-1-pyridiniumolate		C₇H₈ClNO	详情	详情
(II)	12816	3-Methoxy-1-propanol	1589-49-7	C₄H₁₀O₂	详情	详情
(III)	12817	4-(3-methoxypropoxy)-2,3-dimethyl-1-pyridiniumolate		C₁₁H₁₇NO₃	详情	详情
(IV)	12818	[4-(3-methoxypropoxy)-3-methyl-2-pyridinyl]methyl acetate		C₁₃H₁₉NO₄	详情	详情
(V)	12819	[4-(3-Methoxypropoxy)-3-methyl-2-pyridinyl]methanol		C₁₁H₁₇NO₃	详情	详情
(VI)	12820	2-(Chloromethyl)-4-(3-methoxypropoxy)-3-methylpyridine; 2-(Chloromethyl)-3-methyl-4-pyridinyl 3-methoxypropyl ether	117977-20-5	C₁₁H₁₆ClNO₂	详情	详情
(VII)	12821	2-Mercaptobenzinidiazole; 1H-Benzimidazol-2-ylhydrosulfide; 1H-Benzimidazole-2-thiol; 2-Benzimidazolethiol; o-Phenylenethiourea; 2-Benzimidazolinethione; 1,3-Dihydro-2H-benzimidazole-2-thione	583-39-1	C₇H₆N₂S	详情	详情
(VIII)	12822	2-([[4-(3-Methoxypropoxy)-3-methyl-2-pyridinyl]methyl]sulfanyl)-1H-benzimidazole; 2-[(1H-Benzimidazol-2-ylsulfanyl)methyl]-3-methyl-4-pyridinyl 3-methoxypropyl ether	117977-21-6	C₁₈H₂₁N₃O₂S	详情	详情
(IX)	12823	2-([[4-(3-Methoxypropoxy)-3-methyl-2-pyridinyl]methyl]sulfinyl)-1H-benzimidazole; 1H-Benzimidazol-2-yl [4-(3-methoxypropoxy)-3-methyl-2-pyridinyl]methyl sulfoxide		C₁₈H₂₁N₃O₃S	详情	详情

合成路线3

该中间体在本合成路线中的序号：(III)

Cyclization of N-formyl-alpha,alpha-dimethyl-b-phenethylamine (I) with phosphorous pentoxide in refluxing toluene led to isoquinoline (II), which was oxidized with 3-chloroperbenzoic acid (III) in dichloromethane at 0 C to give oxaziridine (IV). Finally, oxazirine (IV) was rearranged with sulfuric acid in aqueous methanol at room temperature to afford the target N-oxide.

参考文献中间体

合成目标

【1】 Carr, A.A.; Thomas, C.E.; Bernotas, R.C.; Ku, G. (Merrell Pharmaceuticals, Inc.); Cyclic nitrones, their preparation and pharmaceutical compsns. containing them. EP 0532027; US 5292746 .

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)	17886	1,1-dimethyl-2-phenylethylformamide		C₁₁H₁₅NO	详情	详情
(II)	17887	3,3-dimethyl-3,4-dihydroisoquinoline		C₁₁H₁₃N	详情	详情
(III)	17888	m-Chloroperbenzoic acid; 3-Chlorobenzenecarboperoxoic acid	937-14-4	C₇H₅ClO₃	详情	详情
(IV)	17889	3,3-dimethyl-4,8b-dihydro-3H-[1,2]oxazireno[3,2-a]isoquinoline		C₁₁H₁₃NO	详情	详情

合成路线4

该中间体在本合成路线中的序号：(III)

The selective reduction of methyl nicotinate (I) with simultaneous protection of the resulting NH group with phenyl chloroformate gives the 1,2-dihydropyridine derivative (II), which is treated with MCPBA (III) to afford the hydroxyester (IV). The reduction of (IV) with Tms-OTf and borane/THF complex affords the allylic alcohol (V), which is oxidized with CrO3 in acetone to provide the ketone (VI). The asymmetric reduction of (VI) with LiAlH4 catalyzed by (-)-N-methyl-ephedrine gives the chiral alcohol (VII), which is treated with refluxing 1N HCl to yield the carboxylic acid (VIII).The reduction of (VIII) with borane/THF complex and H2O2 affords the chiral carbinol (IX), which is finally deprotected by treatment with LiOH to provide the target isofagomine.

参考文献中间体

合成目标

【1】 Zhao, G.; et al.; Selective fowler reductions: Asymmetric total synthesis of isofagomine and other 1-azasugars from methyl nicotinate. Org Lett 2001, 3, 2, 201.

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)	13980	methyl nicotinate; Nicotinic acid, methyl ester	93-60-7	C₇H₇NO₂	详情	详情
(II)	52903	3-methyl 1-phenyl 1,3(2H)-pyridinedicarboxylate		C₁₄H₁₃NO₄	详情	详情
(III)	17888	m-Chloroperbenzoic acid; 3-Chlorobenzenecarboperoxoic acid	937-14-4	C₇H₅ClO₃	详情	详情
(IV)	52904	3-methyl 1-phenyl 5-[(3-chlorobenzoyl)oxy]-6-hydroxy-5,6-dihydro-1,3(2H)-pyridinedicarboxylate		C₂₁H₁₈ClNO₇	详情	详情
(V)	52905	3-methyl 1-phenyl 5-hydroxy-5,6-dihydro-1,3(2H)-pyridinedicarboxylate		C₁₄H₁₅NO₅	详情	详情
(VI)	52906	3-methyl 1-phenyl 5-oxo-5,6-dihydro-1,3(2H)-pyridinedicarboxylate		C₁₄H₁₃NO₅	详情	详情
(VII)	52907	3-methyl 1-phenyl (5S)-5-hydroxy-5,6-dihydro-1,3(2H)-pyridinedicarboxylate		C₁₄H₁₅NO₅	详情	详情
(VIII)	52908	(5S)-5-hydroxy-1-(phenoxycarbonyl)-1,2,5,6-tetrahydro-3-pyridinecarboxylic acid		C₁₃H₁₃NO₅	详情	详情
(IX)	52909	phenyl (3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)-1-piperidinecarboxylate		C₁₃H₁₇NO₅	详情	详情

Extended Information