methyl 2,3-diaminobenzoate -Drug Synthesis Database

【结构式】

【分子编号】18889

【品名】methyl 2,3-diaminobenzoate

【CA登记号】

【分子式】C₈H₁₀N₂O₂

【分子量】166.17968

【元素组成】C 57.82% H 6.07% N 16.86% O 19.26%

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：(I)

The condensation of methyl 2,3-diaminobenzoate (I) with isatin (II) in refluxing AcOH afforded a mixture of indoloquinoxaline-carboxylates (III) and (IV), which were separated by column chromatography. The desired 4-carboxylate isomer (III) was methylated at the indole N atom with CH3I in the presence of NaH to provide (V). The ester group of (V) was reduced to alcohol (VI) with LiAlH4 and then oxidized with activated MnO2 to yield aldehyde (VII). Subsequent condensation of (VII) with amine (VIII) in refluxing toluene in the presence of p-toluenesulfonic acid produced the corresponding imine (IX), which was finally reduced with NaBH4 in EtOH to the target amine, which was isolated as the hydrochloride salt.

参考文献中间体

合成目标

【1】 Matsumoto, T.; Wada, H.; Migita, Y.; Hatayama, K.; Sekiguchi, Y. (Taisho Pharmaceutical Co., Ltd.); Indolo[2,3-b]quinoxaline derivs.. EP 0695754; JP 1995522993; WO 9424135 .

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)	18889	methyl 2,3-diaminobenzoate		C₈H₁₀N₂O₂	详情	详情
(II)	14098	2,3-Indolinedione; 1H-Indole-2,3-dione; Isatin	91-56-5	C₈H₅NO₂	详情	详情
(III)	18891	methyl 6H-indolo[2,3-b]quinoxaline-4-carboxylate		C₁₆H₁₁N₃O₂	详情	详情
(IV)	18892	methyl 6H-indolo[2,3-b]quinoxaline-1-carboxylate		C₁₆H₁₁N₃O₂	详情	详情
(V)	18893	methyl 6-methyl-6H-indolo[2,3-b]quinoxaline-4-carboxylate		C₁₇H₁₃N₃O₂	详情	详情
(VI)	18894	(6-methyl-6H-indolo[2,3-b]quinoxalin-4-yl)methanol		C₁₆H₁₃N₃O	详情	详情
(VII)	18895	6-methyl-6H-indolo[2,3-b]quinoxaline-4-carbaldehyde		C₁₆H₁₁N₃O	详情	详情
(VIII)	11770	2-Amino-2-methyl-1,3-propanediol	115-69-5	C₄H₁₁NO₂	详情	详情
(IX)	18897	2-methyl-2-[[(Z)-(6-methyl-6H-indolo[2,3-b]quinoxalin-4-yl)methylidene]amino]-1,3-propanediol		C₂₀H₂₀N₄O₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(V)

Regioselective ring opening of 3-nitrophthalic anhydride (I) with ammonia yielded amide (II), which was subjected to a Hofmann degradation with Br2 and KOH to afford 3-nitroanthranilic acid (III). Esterification of (III) to ster (IV) using MeOH/HCl, followed by reduction of the nitro group by catalytic hydrogenation, gave methyl 2,3-diaminobenzoate (V). Alternatively, diamino ester (V) was prepared by reduction of nitro acid (III), followed by catalytic esterification. Methyl 2,3-diaminobenzoate (V) was then selectively acylated at the 3-amino group with 4-methoxybenzoyl chloride (VI) producing amide (VII), which was cyclized to the benzimidazole (VIII) upon refluxing in HOAc. The corresponding amide (IX) was obtained by reaction of ester (VIII) with liquid ammonia at 100 C in a pressure vessel. Finally, the methyl ether group of (IX) was cleaved to the title phenol by treatment with boron tribromide.

参考文献中间体

合成目标

【1】 Wood, M.D.; Taylor, S.G.; Reavill, C.; et al.; Pharmacological actions of a novel, high-affinity, and selective human dopamine D3 receptor antagonist, SB-277011-A. J Pharmacol Exp Ther 2000, 294, 3, 1154.
【2】 Griffin, R.J.; Calvert, A.H.; Newell, D.R.; Curtain, J.N.; Golding, B.T. (University of Newcastle upon Tyne); Benzimidazole cpds.. US 6100283 .

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)	46407	4-nitro-2-benzofuran-1,3-dione；3-nitrophthalic anhydride	641-70-3	C₈H₃NO₅	详情	详情
(II)	46408	2-(aminocarbonyl)-3-nitrobenzoic acid		C₈H₆N₂O₅	详情	详情
(III)	46409	2-amino-3-nitrobenzoic acid		C₇H₆N₂O₄	详情	详情
(IV)	46410	methyl 2-amino-3-nitrobenzoate		C₈H₈N₂O₄	详情	详情
(V)	18889	methyl 2,3-diaminobenzoate		C₈H₁₀N₂O₂	详情	详情
(VI)	22671	4-Methoxybenzoyl chloride; p-Methoxybenzoyl chloride; 4-Anisoyl chloride	100-07-2	C₈H₇ClO₂	详情	详情
(VII)	46411	methyl 2-amino-3-[(4-methoxybenzoyl)amino]benzoate		C₁₆H₁₆N₂O₄	详情	详情
(VIII)	46412	methyl 2-(4-methoxyphenyl)-1H-benzimidazole-4-carboxylate		C₁₆H₁₄N₂O₃	详情	详情
(IX)	46413	2-(4-methoxyphenyl)-1H-benzimidazole-4-carboxamide		C₁₅H₁₃N₃O₂	详情	详情

Extended Information