tert-butyl 2-[3-amino-6-methyl-2-oxo-1(2H)-pyridinyl]acetate -Drug Synthesis Database

【结构式】

【分子编号】26605

【品名】tert-butyl 2-[3-amino-6-methyl-2-oxo-1(2H)-pyridinyl]acetate

【CA登记号】

【分子式】C₁₂H₁₈N₂O₃

【分子量】238.2866

【元素组成】C 60.49% H 7.61% N 11.76% O 20.14%

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：(XII)

The intermediate 2-[3-(benzylsulfonamido)-6-methyl-2-oxo-1,2-dihydropyridin-1-yl]acetic acid (VI) has been obtained as follows: The reaction of 2-hydroxy-6-methylpyridine-3-carboxylic acid (IX) with diphenylphosphoryl azide (DPPA), triethylamine and benzyl alcohol in refluxing dioxane gives 3-(benzyloxycarbonylamino)-6-methylpyridin-2(1H)-one (X), which is condensed with tert-butyl bromoacetate (II) by means of NaH in THF yielding the expected condensation product (XI). The deprotection od the amino group of (XI) with H2 over Pd/C in ethanol/water gives the aminopyridone (XII), which is acylated with benzylsulfonylchloride (XIII) in pyridine yielding the sulfonamide (XIV). Finally, the tert-butyl ester group of (XIV) is hydrolyzed with HCl in ethyl acetate to afford the target intermediate (VI).

参考文献中间体

合成目标

【1】 Naylor-Olsen, A.M.; Newton, C.L.; Isaacs, R.C.A.; Dorsey, B.D. (Merck & Co., Inc.); Thrombin inhibitors. EP 0969840; US 5932606; WO 9842342 .

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)	26599	2-[3-[(benzylsulfonyl)amino]-6-methyl-2-oxo-1(2H)-pyridinyl]acetic acid		C₁₅H₁₆N₂O₅S	详情	详情
(IX)	26602	2-hydroxy-6-methylnicotinic acid	38116-61-9	C₇H₇NO₃	详情	详情
(X)	26603	benzyl 6-methyl-2-oxo-1,2-dihydro-3-pyridinylcarbamate		C₁₄H₁₄N₂O₃	详情	详情
(XI)	26604	tert-butyl 2-[3-[[(benzyloxy)carbonyl]amino]-6-methyl-2-oxo-1(2H)-pyridinyl]acetate		C₂₀H₂₄N₂O₅	详情	详情
(XII)	26605	tert-butyl 2-[3-amino-6-methyl-2-oxo-1(2H)-pyridinyl]acetate		C₁₂H₁₈N₂O₃	详情	详情
(XIII)	25151	phenylmethanesulfonyl chloride	1939-99-7	C₇H₇ClO₂S	详情	详情
(XIV)	26606	tert-butyl 2-[3-[(benzylsulfonyl)amino]-6-methyl-2-oxo-1(2H)-pyridinyl]acetate		C₁₉H₂₄N₂O₅S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XIV)

Synthesis of intermediate (VI): Treatment of pyridone (X) with diphenyl phosphoryl azide (DPPA) followed by reaction with benzyl alcohol affords the protected derivative (XI), which then reacts with tert-butyl bromoacetate (XII) by means of Cs2CO3 to provide the acetate derivative (XIII). Hydrogenation of (XIII) over Pd/C allows Cbz removal, giving amine (XIV), which is then condensed with iodo derivative (XV) to furnish sulfonamide compound (XVI). Finally, hydrolysis of (XVI) is achieved by treatment with TFA to afford the target intermediate (VI).

参考文献中间体

合成目标

【1】 Soll, R.M.; Lu, T.; Tomczuk, B.E.; Spurlino, J.; Pan, W.; Bone, R.; Green, D.W.; Heteroaryl keto thrombin inhibitors: Design and synthesis. 220th ACS Natl Meet (Aug 20 2000, Washington DC) 2000, Abst MEDI 285.
【2】 Tumczuk, B.E.; Pan, W.; Soll, R.M.; Lu, T. (3-Dimensional Pharmaceuticals, Inc.); Heteroaryl protease inhibitors and diagnostic imaging agents. WO 0104117 .

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)	44786	2-[3-[[(2-iodobenzyl)sulfonyl]amino]-6-methyl-2-oxo-1(2H)-pyridinyl]acetic acid		C₁₅H₁₅IN₂O₅S	详情	详情
(X)	44789	6-methyl-2-oxo-1,2-dihydro-3-pyridinecarboxylic acid		C₇H₇NO₃	详情	详情
(XI)	26603	benzyl 6-methyl-2-oxo-1,2-dihydro-3-pyridinylcarbamate		C₁₄H₁₄N₂O₃	详情	详情
(XII)	17430	2-Bromoacetic acid tert-butyl ester; tert-butyl 2-bromoacetate; tert-Butyl bromoacetate	5292-43-3	C₆H₁₁BrO₂	详情	详情
(XIII)	26604	tert-butyl 2-[3-[[(benzyloxy)carbonyl]amino]-6-methyl-2-oxo-1(2H)-pyridinyl]acetate		C₂₀H₂₄N₂O₅	详情	详情
(XIV)	26605	tert-butyl 2-[3-amino-6-methyl-2-oxo-1(2H)-pyridinyl]acetate		C₁₂H₁₈N₂O₃	详情	详情
(XV)	44791	(2-iodophenyl)methanesulfonyl chloride		C₇H₆ClIO₂S	详情	详情
(XVI)	44790	tert-butyl 2-[3-[[(2-iodobenzyl)sulfonyl]amino]-6-methyl-2-oxo-1(2H)-pyridinyl]acetate		C₁₉H₂₃IN₂O₅S	详情	详情

Extended Information