M-55551, -Drug Synthesis Database

【结构式】

【药物名称】M-55551

【化学名称】4-(6-Chloronaphthalen-2-ylsulfonyl)-6-oxo-1-[1-(4-pyridyl)piperidin-4-ylmethyl]piperazine-2(R)-carboxylic acid

【CA登记号】229646-76-8, 229647-04-5 (methanesulfonate), 229646-52-0 (undefined stereoch.)

【分子式】C₂₆H₂₇ClN₄O₅S

【分子量】543.04589

【开发单位】Mochida (Originator)

【药理作用】Anticoagulants, Coagulation Disorders Therapy, HEMATOLOGIC DRUGS, Coagulation Factor Xa Inhibitors

合成路线1

Swern oxidation of 1-(4-pyridinyl)-4-piperidinemethanol (I) affords aldehyde (II). Reductive amination of (II) with the (R)-diaminopropionic acid derivative (III) in the presence of NaBH(OAc)3 yields (IV). Subsequent acylation of (IV) with bromoacetyl chloride (V) provides bromoacetamide (VI). Acidic cleavage of the N-Boc group of (VI), followed by cyclization in the presence of triethylamine leads to piperazinone (VII). Sulfonylation of amine (VII) with 6-chloro-2-naphthalenesulfonyl chloride (VIII) gives (IX). Finally, the target carboxylic acid is obtained by hydrolysis of ethyl ester (IX) under acidic conditions.

参考文献中间体

【1】 Nishida, H.; Miyazaki, Y.; Mukaihira, T.; Saitoh, F.; Fukui, M.; Harada, K.; Itoh, M.; Muraoka, A.; Matsusue, T.; Okamoto, A.; Hosaka, Y.; Matsumoto, M.; Ohnishi, S.; Mochizuki, H.; Synthesis and evaluation of 1-arylsulfonyl-3-piperazinone derivatives as a factor Xa inhibitor II. Substituent effect on biological activities. Chem Pharm Bull 2002, 50, 9, 1187.
【2】 Miyazaki, Y.; Mukaihira, T.; Nishida, H.; Hosaka, Y.; Matsusue, T. (Mochida Pharmaceutical Co., Ltd.); Aromatic cpds. having cyclic amino or salts thereof. EP 1048652; WO 9933805 .

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)	45860	[1-(4-pyridinyl)-4-piperidinyl]methanol		C₁₁H₁₆N₂O	详情	详情
(II)	52205	1-(4-pyridinyl)-4-piperidinecarbaldehyde		C₁₁H₁₄N₂O	详情	详情
(III)	45862	ethyl (2R)-2-amino-3-[(tert-butoxycarbonyl)amino]propanoate		C₁₀H₂₀N₂O₄	详情	详情
(IV)	45863	ethyl (2R)-3-[(tert-butoxycarbonyl)amino]-2-([[1-(4-pyridinyl)-4-piperidinyl]methyl]amino)propanoate		C₂₁H₃₄N₄O₄	详情	详情
(V)	27903	2-Bromoacetyl chloride	22118-09-8	C₂H₂BrClO	详情	详情
(VI)	45864	ethyl (2R)-2-((2-bromoacetyl)[[1-(4-pyridinyl)-4-piperidinyl]methyl]amino)-3-[(tert-butoxycarbonyl)amino]propanoate		C₂₃H₃₅BrN₄O₅	详情	详情
(VII)	61247	ethyl (2R)-6-oxo-1-{[1-(4-pyridinyl)-4-piperidinyl]methyl}-2-piperazinecarboxylate		C₁₈H₂₆N₄O₃	详情	详情
(VIII)	45865	6-chloro-2-naphthalenesulfonyl chloride		C₁₀H₆Cl₂O₂S	详情	详情
(IX)	45866	ethyl (2R)-4-[(6-chloro-2-naphthyl)sulfonyl]-6-oxo-1-[[1-(4-pyridinyl)-4-piperidinyl]methyl]-2-piperazinecarboxylate		C₂₈H₃₁ClN₄O₅S	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(2)