methyl 2-amino-3-methylbenzoate -Drug Synthesis Database

【结构式】

【分子编号】48424

【品名】methyl 2-amino-3-methylbenzoate

【CA登记号】

【分子式】C₉H₁₁NO₂

【分子量】165.19188

【元素组成】C 65.44% H 6.71% N 8.48% O 19.37%

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)

Sulfonylation of methyl 3-methylanthranilate (I) with 4-methoxybenzenesulfonyl chloride (II) provided the sulfonamide (III). This was then N-alkylated with 3-picolyl chloride hydrochloride (IV) in the presence of K2CO3 to afford (V). Ester (V) hydrolysis with LiOH or NaOH provided carboxylic acid (VI), which was further activated as the corresponding acid chloride (VII) using oxalyl chloride in the presence of DMF. Coupling of acid chloride (VII) with hydroxylamine hydrochloride furnished the target hydroxamic acid, which was finally treated with HCl to produce the title hydrochloride salt.

参考文献中间体

合成目标

【1】 Levin, J.I.; DiJoseph, J.F.; Du, M.T.; et al.; The discovery of anthranilic acid-based MMP inhibitors. Part 1. SAR of the 3-position. Bioorg Med Chem Lett 2001, 11, 2, 235.
【2】 Gu, Y.; Nelson, F.C.; Zask, A.; Du, M.T.; Levin, J.I.; Venkatesan, M. (American Cyanamid Co.); Preparation and use of orthosulfonamido aryl hydroxamic acids as matrix metalloproteinase and TACE inhibitors. US 5929097 .
【3】 Nelson, F.C.; Venkatesan, A.M.; Levin, J.I.; Du, M.T.; Gu, Y.; Zask, A. (American Cyanamid Co.); The preparation and use of ortho-sulfonamido aryl hydroxamic acids as matrix metalloproteinase and TACE inhibitors. WO 9816503 .

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)	48424	methyl 2-amino-3-methylbenzoate		C₉H₁₁NO₂	详情	详情
(II)	15719	4-methoxybenzenesulfonyl chloride	98-68-0	C₇H₇ClO₃S	详情	详情
(III)	48425	methyl 2-[[(4-methoxyphenyl)sulfonyl]amino]-3-methylbenzoate		C₁₆H₁₇NO₅S	详情	详情
(IV)	15793	3-(Chloromethyl)pyridine	3099-31-8	C₆H₆ClN	详情	详情
(V)	48426	methyl 2-[[(4-methoxyphenyl)sulfonyl](3-pyridinylmethyl)amino]-3-methylbenzoate		C₂₂H₂₂N₂O₅S	详情	详情
(VI)	48427	2-[[(4-methoxyphenyl)sulfonyl](3-pyridinylmethyl)amino]-3-methylbenzoic acid		C₂₁H₂₀N₂O₅S	详情	详情
(VII)	48428	2-[[(4-methoxyphenyl)sulfonyl](3-pyridinylmethyl)amino]-3-methylbenzoyl chloride		C₂₁H₁₉ClN₂O₄S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

Acylation of methyl 3-methylanthranilate (I) with 4-(4-pyridyloxy)benzenesulfonyl chloride (II) gave sulfonamide (III). Subsequent N-alkylation of the sulfonamide function with iodomethane in the presence of NaH afforded the N-methyl sulfonamide (IV). Basic hydrolysis of the ester group of (IV) yielded carboxylic acid (V), which was further activated as the acid chloride (VI) upon treatment with oxalyl chloride. Finally, reaction of acid chloride (VI) with hydroxylamine yielded the corresponding hydroxamic acid.

参考文献中间体

合成目标

【1】 Levin, J.I.; et al.; The discovery of anthranilic acid-based MMP inhibitors. Part 2: SAR of the 5-position P11 groups. Bioorg Med Chem Lett 2001, 11, 16, 2189.
【2】 Gu, Y.; Nelson, F.C.; Zask, A.; Du, M.T.; Levin, J.I.; Venkatesan, M. (American Cyanamid Co.); Preparation and use of orthosulfonamido aryl hydroxamic acids as matrix metalloproteinase and TACE inhibitors. US 5929097 .
【3】 Nelson, F.C.; Venkatesan, A.M.; Levin, J.I.; Du, M.T.; Gu, Y.; Zask, A. (American Cyanamid Co.); The preparation and use of ortho-sulfonamido aryl hydroxamic acids as matrix metalloproteinase and TACE inhibitors. WO 9816503 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	48424	methyl 2-amino-3-methylbenzoate	C₉H₁₁NO₂	详情	详情
(II)	32887	4-(4-pyridinyloxy)benzenesulfonyl chloride	C₁₁H₈ClNO₃S	详情	详情
(III)	51112	methyl 3-methyl-2-([[4-(4-pyridinyloxy)phenyl]sulfonyl]amino)benzoate	C₂₀H₁₈N₂O₅S	详情	详情
(IV)	51113	methyl 3-methyl-2-(methyl[[4-(4-pyridinyloxy)phenyl]sulfonyl]amino)benzoate	C₂₁H₂₀N₂O₅S	详情	详情
(V)	51114	3-methyl-2-(methyl[[4-(4-pyridinyloxy)phenyl]sulfonyl]amino)benzoic acid	C₂₀H₁₈N₂O₅S	详情	详情
(VI)	51115	3-methyl-2-(methyl[[4-(4-pyridinyloxy)phenyl]sulfonyl]amino)benzoyl chloride	C₂₀H₁₇ClN₂O₄S	详情	详情

Extended Information