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【结 构 式】 
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【药物名称】M-55113 【化学名称】4-(6-Chloronaphthalen-2-ylsulfonyl)-1-[1-(4-pyridyl)piperidin-4-ylmethyl]piperazin-2-one 【CA登记号】229646-37-1, 239071-44-4 (monohydrochloride), 229646-85-9 (monomethanesufonate salt) 【 分 子 式 】C25H27ClN4O3S 【 分 子 量 】499.03594 |
【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
The condensation of 4-piperidinylmethanol (I) with 4-chloropyridine (II) gives 1-(4-pyridyl)piperidin-4-ylmethanol (III), which is oxidized with (COCl)2 and TEA in DMSO to yield the carbaldehyde (IV). The reductocondensation of (IV) with N-(tert-butoxycarbonyl)ethylene-1,2-diamine (V) by means of sodium triacetoxyborohydride and acetic acid affords the corresponding adduct as the borane complex (VI), which is acylated with bromoacetyl chloride (VII) and TEA in dichloromethane, providing the bromoacetamide (VIII). The cleavage of the boron complex and the Boc protecting group of (VIII) with TFA and anisole in ethyl ether gives the precursor (IX), which is cyclized to the piperazinone (X) by means of TEA in DMF. Finally, compound (X) is condensed with 6-chloronaphthalene-2-sulfonyl chloride by means of TEA in dichloromethane to yield the target sulfonamide.
| 【1】 Nishida, H.; et al.; Synthesis and evaluation of 1-arylsulfonyl-3-piperazinone derivatives as factor Xa inhibitor. Chem Pharm Bull 2001, 49, 10, 1237. |
| 【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) | 32954 | 4-piperidinylmethanol | C6H13NO | 详情 | 详情 | |
| (II) | 32889 | 4-chloropyridine | 7379-35-3 | C5H4ClN | 详情 | 详情 |
| (III) | 45860 | [1-(4-pyridinyl)-4-piperidinyl]methanol | C11H16N2O | 详情 | 详情 | |
| (IV) | 52205 | 1-(4-pyridinyl)-4-piperidinecarbaldehyde | C11H14N2O | 详情 | 详情 | |
| (V) | 13241 | N-Boc-ethylenediamine;tert-butyl (2-aminoethyl)carbamate；tert-butyl 2-aminoethylcarbamate; tert-Butyl n-(2-aminoethyl)carbamate | 57260-73-8 | C7H16N2O2 | 详情 | 详情 |
| (VI) | 52206 | C22H37BN4O7 | 详情 | 详情 | ||
| (VII) | 27903 | 2-Bromoacetyl chloride | 22118-09-8 | C2H2BrClO | 详情 | 详情 |
| (VIII) | 52207 | C24H38BBrN4O8 | 详情 | 详情 | ||
| (IX) | 52208 | N-(2-aminoethyl)-2-bromo-N-{[1-(4-pyridinyl)-4-piperidinyl]methyl}acetamide | C15H23BrN4O | 详情 | 详情 | |
| (X) | 52209 | 1-{[1-(4-pyridinyl)-4-piperidinyl]methyl}-2-piperazinone | C15H22N4O | 详情 | 详情 | |
| (XI) | 45865 | 6-chloro-2-naphthalenesulfonyl chloride | C10H6Cl2O2S | 详情 | 详情 |