【结 构 式】 |
【分子编号】58455 【品名】8-(chloromethyl)-10H-pyrazino[2,3-b][1,4]benzothiazine 【CA登记号】 |
【 分 子 式 】C11H8ClN3S 【 分 子 量 】249.72344 【元素组成】C 52.91% H 3.23% Cl 14.2% N 16.83% S 12.84% |
合成路线1
该中间体在本合成路线中的序号:(VII)Displacement of the chloride group of 4-chloro-3-nitrobenzoic acid (I) with sodium disulfide, followed by reduction of the disulfide and nitro groups with Sn/HCl yields 3-amino-4-mercaptobenzoic acid (II), which is further esterified to (III) with methanolic HCl. Condensation of (III) with 2,3-dichloropyrazine (IV) produces the pyrazinobenzothiazine compound (V). The ester group of (V) is then reduced to alcohol (VI) employing LiAlH4. Subsequent treatment of alcohol (VI) with methanesulfonyl chloride and pyridine leads to the benzyl chloride (VII).
【1】 Kaneko, T.; et al.; Inhibitors of adhesion molecules expression: The synthesis and pharmacological properties of 10H-pyrazino[2,3-b][1,4]benzothiazine derivatives. Chem Pharm Bull 2002, 50, 7, 922. |
【2】 Kaneko, T.; Clark, R.; Ohi, N.; Ozaki, F.; Kawahara, T.; Kamada, A.; Okano, K.; Yokohama, H.; Muramoto, K.; Arai, T.; Ohkuro, M.; Takenaka, O.; Sonoda, J. (Eisai Co., Ltd.); Benzopiperidine derivs.. EP 0934941; WO 9806720 . |
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) | 14485 | 3-nitro-4-chlorobenzoic acid; 4-chloro-3-nitrobenzoic acid | 96-99-1 | C7H4ClNO4 | 详情 | 详情 |
(II) | 58451 | 3-amino-4-sulfanylbenzoic acid | C7H7NO2S | 详情 | 详情 | |
(III) | 58452 | methyl 3-amino-4-sulfanylbenzoate | C8H9NO2S | 详情 | 详情 | |
(IV) | 32326 | 2,3-dichloropyrazine | 4858-85-9 | C4H2Cl2N2 | 详情 | 详情 |
(V) | 58453 | methyl 10H-pyrazino[2,3-b][1,4]benzothiazine-8-carboxylate | C12H9N3O2S | 详情 | 详情 | |
(VI) | 58454 | 10H-pyrazino[2,3-b][1,4]benzothiazin-8-ylmethanol | C11H9N3OS | 详情 | 详情 | |
(VII) | 58455 | 8-(chloromethyl)-10H-pyrazino[2,3-b][1,4]benzothiazine | C11H8ClN3S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号:(VII)4-Amino-1-benzylpiperidine (VIII) is condensed with dimethylsulfamoyl chloride to give the sulfamide (IX). Subsequent benzyl group hydrogenolysis in (IX) over Pd/C provides the piperidine (X). Finally, alkylation of piperidine (X) with chloride (VII) yields the title compound.
【1】 Kaneko, T.; et al.; Inhibitors of adhesion molecules expression: The synthesis and pharmacological properties of 10H-pyrazino[2,3-b][1,4]benzothiazine derivatives. Chem Pharm Bull 2002, 50, 7, 922. |
【2】 Kaneko, T.; Clark, R.; Ohi, N.; Ozaki, F.; Kawahara, T.; Kamada, A.; Okano, K.; Yokohama, H.; Muramoto, K.; Arai, T.; Ohkuro, M.; Takenaka, O.; Sonoda, J. (Eisai Co., Ltd.); Benzopiperidine derivs.. EP 0934941; WO 9806720 . |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(VII) | 58455 | 8-(chloromethyl)-10H-pyrazino[2,3-b][1,4]benzothiazine | C11H8ClN3S | 详情 | 详情 | |
(VIII) | 34808 | 1-Benzyl-4-piperidinylamine; 1-Benzyl-4-piperidinamine; 4-Amino-1-benzylpiperidine | 50541-93-0 | C12H18N2 | 详情 | 详情 |
(IX) | 58456 | N'-(1-benzyl-4-piperidinyl)-N,N-dimethylsulfamide | C14H23N3O2S | 详情 | 详情 | |
(X) | 58457 | N,N-dimethyl-N'-(4-piperidinyl)sulfamide | C7H17N3O2S | 详情 | 详情 |