Zhejiang Haisen Pharmaceutical Co., Ltd.

A new synthetic method of 5-cyanophthalide as an important intermediate of citalopram was established.The compound 5-cyanophthalide I was prepared by reaction of 5-formylphthalide with hydroxylamine hydrochloride at reflux conditions for 40 min in formic acid (5-formylphthalide:hydroxylamine hydrochloride = 1:1.2 mol/mol).The yield rate could reach to 83%.This method was simple in technol. with high yields, low cost and better application prospect.

(S)-10-(1-carbamoylcyclopropyl)-9-fluoro-3-methyl-7-oxo-3,7-dihydro-2H-[1,4]-oxazino [2,3,4-ij] quinoline-6-carboxylic acid, the senior intermediate of pazufloxacin, was synthesized from (S)-Et 10-(cyanomethyl)-9-fluoro-3-methyl-7-oxo-3,7-dihydro-2H-[1,4] oxazino [2,3,4-ij] quinoline-6-carboxylate via a one-pot reaction of cyclopropanation and cyanide hydrolyzation.The reaction conditions were optimized as follows: n(compound II) : n(1,2-dichloroethane): n(benzyltriethylammonium chloride) : n(NaOH) = 1:1.5:0.43:16.7, stirred in water for 5 h at room temperature and then at 70°C for 2 h.Under such optimum conditions, the yield of the product was 82%.The method has the advantages of mild reaction conditions, safety, low cost, and environment-friendliness.

The impurity 4-N-demethylanalgin formed in preparing analgin and its causes were analyzed to synthesize it in laboratory4-N-demethylanalgin is prepared by the reflux reaction of aminoantipyrine (AA) with sodium pyrosulphite and formaldehyde for 40 min in ethanol (pure aminoantipyrine: sodium pyrosulphite: formaldehyde=1:0.65:1.1) and the yield rate was 67%-73%.4-N-demethylanalgin is formed by the condensation reaction of AA with sodium pyrosulphite and formaldehyde in the production process of analgin.