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【结 构 式】 
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【分子编号】25191 【品名】isonicotinamide 【CA登记号】1453-82-3 |
【 分 子 式 】C6H6N2O 【 分 子 量 】122.12652 【元素组成】C 59.01% H 4.95% N 22.94% O 13.1% |
合成路线1
该中间体在本合成路线中的序号：(IV)The reaction of 7-aminocephalosporanic acid (I) with alpha-sulfophenylacetyl chloride (II) by means of NaOH and NaHCO3 in ether gives 7-(alpha-sulfophenylacetamido)cephalosporanic acid (III), which is then condensed with isonicotinamide (IV) by means of KSCN and pyridine in water.
| 【1】 Nomura, H.; et al.; Semisynthetic beta-lactams antibiotics. VII. New semisynthetic cephalosporins derived from alpha-sulfophenylacetic acid. Heterocycles 1974, 2, 1, 67-72. |
| 【2】 Morimoto, S.; et al.; Cephalosporin compounds. DE 2234280; ES 404745; FR 2146313; NL 7209811 . |
| 【3】 Nomura, H.; et al.; Semisynthetic beta-lactam antibiotics. 6. Sulfocephalosporins and their antipseudomonal activities. J Med Chem 1974, 17, 12, 1312-15. |
| 【4】 Blancafort, P.; Castaner, J.; Serradell, M.N.; Sweetman, A.J.; Cefsulodin. Drugs Fut 1980, 5, 2, 67. |
| 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) | 22747 | (6R,7R)-3-[(acetoxy)methyl]-7-amino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid | C10H12N2O5S | 详情 | 详情 | |
| (II) | 32665 | (1S)-2-chloro-2-oxo-1-phenyl-1-ethanesulfonic acid | C8H7ClO4S | 详情 | 详情 | |
| (III) | 32666 | (6R,7R)-3-[(acetoxy)methyl]-8-oxo-7-[[(2S)-2-phenyl-2-sulfoethanoyl]amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid | C18H18N2O9S2 | 详情 | 详情 | |
| (IV) | 25191 | isonicotinamide | 1453-82-3 | C6H6N2O | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(I)Condensation of isonicotinamide (I) with 1-chloro-2,4-dinitrobenzene (II) gave quaternary pyridinium salt (III). This was further converted into pyridinium salt (V) by treatment with 2-methoxyaniline (IV) in MeOH. Catalytic transfer hydrogenation of the pyridine ring of (V) provided piperidine (VI). The amide function of (VI) was then reduced to amine (VII) using either borane-dimethyl sulfide complex or LiAlH4. Condensation of 4-chlorocatechol (VIII) with epichlorohydrin (IX) in aqueous KOH produced a mixture of regioisomeric benzodioxans (X) and (XI), from which the major 7-chloro isomer (X) was isolated by flash chromatography after treatment with tosyl chloride and pyridine yielding tosylate (XII). This compound was finally coupled with amine (VII) in the presence of K2CO3 and KI in boiling acetonitrile.
| 【1】 Kerrigan, F.; Heal, D.J.; Martin, K.F. (The Boots Company plc); Bicyclic aromatic cpds. as therapeutic agents. EP 0717739; JP 1997502431; US 5767116; WO 9507274 . |
| 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) | 25191 | isonicotinamide | 1453-82-3 | C6H6N2O | 详情 | 详情 |
| (II) | 10378 | 1-Chloro-2,4-dinitrobenzene | 97-00-7 | C6H3ClN2O4 | 详情 | 详情 |
| (III) | 25192 | 4-(aminocarbonyl)-1-(2,4-dinitrophenyl)pyridinium chloride | 475-25-2 | C12H9ClN4O5 | 详情 | 详情 |
| (IV) | 25193 | 2-methoxyphenylamine; 2-methoxyaniline | 517-28-2 | C7H9NO | 详情 | 详情 |
| (V) | 25194 | 4-(aminocarbonyl)-1-(2-methoxyphenyl)pyridinium chloride | C13H13ClN2O2 | 详情 | 详情 | |
| (VI) | 25195 | 1-(2-methoxyphenyl)-4-piperidinecarboxamide | C13H18N2O2 | 详情 | 详情 | |
| (VII) | 25196 | [1-(2-methoxyphenyl)-4-piperidinyl]methylamine; [1-(2-methoxyphenyl)-4-piperidinyl]methanamine | C13H20N2O | 详情 | 详情 | |
| (VIII) | 25197 | 4-chloro-1,2-benzenediol | 2138-22-9 | C6H5ClO2 | 详情 | 详情 |
| (IX) | 10146 | Epichlorohydrin; 2-(Chloromethyl)oxirane | 106-89-8 | C3H5ClO | 详情 | 详情 |
| (X) | 25199 | (7-chloro-2,3-dihydro-1,4-benzodioxin-2-yl)methanol | C9H9ClO3 | 详情 | 详情 | |
| (XI) | 25198 | (6-chloro-2,3-dihydro-1,4-benzodioxin-2-yl)methanol | C9H9ClO3 | 详情 | 详情 | |
| (XII) | 25200 | (7-chloro-2,3-dihydro-1,4-benzodioxin-2-yl)methyl 4-methylbenzenesulfonate | C16H15ClO5S | 详情 | 详情 |
