-Drug Synthesis Database

【结构式】

【药物名称】

【化学名称】N-[3-(Guanidinooxy)-1(S)-(thiazol-2-ylcarbonyl)propyl]-3-(2-iodobenzylsulfonamido)-6-methyl-2-oxo-1,2-dihydropyridine-1-acetamide

【CA登记号】

【分子式】C₂₃H₂₆IN₇O₆S₂

【分子量】687.53937

【开发单位】3-Dimensional (Originator)

【药理作用】Anticoagulants, Coagulation Disorders Therapy, DIAGNOSTIC AGENTS, HEMATOLOGIC DRUGS, Radiopharmaceuticals, Thrombin Inhibitors

合成路线1 合成路线2

合成路线1

Synthetic pathway for obtaining EN 292685: Treatment of amino acid (I) with CbzOSu affords the protected amino acid (II), which is further protected by means of Boc2O to yield derivative (III). Condensation of amino acid (III) with N,O-dimethyl hydroxylamine by means of BOP and DIEA provides hydroxamic ester (IV), which is then subjected to hydrogenolysis over Pd/C in CHCl3 for selective deprotection, furnishing compound (V). Coupling of (V) to intermediate (VI) affords derivative (VII), which is then coupled to lithium derivative (VIII) to give protected compound (IX). Finally, the Boc group of (IX) is removed by treatment with TFA.

参考文献中间体

【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	分子式	供应商	用于合成
(I)	44766	(2S)-2-amino-4-([[amino(imino)methyl]amino]oxy)butyric acid	C₅H₁₂N₄O₃	详情	详情
(II)	44767	5-[4-[(5-methoxy-3-methyl-3H-imidazo[4,5-b]pyridin-2-yl)methoxy]benzyl]-3-trityl-1,3-thiazolidine-2,4-dione	C₃₈H₃₂N₄O₄S	详情	详情
(III)	44775	(11S)-11-[[(benzyloxy)carbonyl]amino]-6-imino-2,2-dimethyl-4-oxo-3,8-dioxa-5,7-diazadodecan-12-oic acid	C₁₈H₂₆N₄O₇	详情	详情
(IV)	44776	benzyl (1S)-6-imino-1-[[methoxy(methyl)amino]carbonyl]-10,10-dimethyl-8-oxo-4,9-dioxa-5,7-diazaundec-1-ylcarbamate	C₂₀H₃₁N₅O₇	详情	详情
(V)	44785	tert-butyl (6S)-6-amino-8-methyl-7-oxo-3,9-dioxa-2,8-diazadec-1-animidoylcarbamate	C₁₂H₂₅N₅O₅	详情	详情
(VI)	44786	2-[3-[[(2-iodobenzyl)sulfonyl]amino]-6-methyl-2-oxo-1(2H)-pyridinyl]acetic acid	C₁₅H₁₅IN₂O₅S	详情	详情
(VII)	44787	tert-butyl (6S)-6-([2-[3-[[(2-iodobenzyl)sulfonyl]amino]-6-methyl-2-oxo-1(2H)-pyridinyl]acetyl]amino)-8-methyl-7-oxo-3,9-dioxa-2,8-diazadec-1-animidoylcarbamate	C₂₇H₃₈IN₇O₉S	详情	详情
(VIII)	23162	1,3-thiazol-2-yllithium	C₃H₂LiNS	详情	详情
(IX)	44788	tert-butyl imino([[(3S)-3-([2-[3-[[(2-iodobenzyl)sulfonyl]amino]-6-methyl-2-oxo-1(2H)-pyridinyl]acetyl]amino)-4-oxo-4-(1,2lambda(5),3-thiadiazol-2-yl)butyl]oxy]amino)methylcarbamate	C₂₇H₃₅IN₈O₈S₂	详情	详情

合成路线2

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

【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

Drug NewChemical Entity Original Patent(1)