目的 研發(fā)一種新型唑烷酮類抗生素（（3R，3aS）-7-（6-（（S）3-甲基-2-（口惡）唑烷酮-5-基）吡啶-3-基）-1-氧-1，3，3a，4-四氫苯并[b]（口惡）唑[3，4-d][1，4]（口惡）嗪-3-基）甲基）磷酸單酯（TJ1508）的合成工藝，并研究其晶型。方法 以磷酸二芐酯中間體為原料，通過酸催化脫芐基得到TJ1508，在不同的溶劑體系中析晶得到不同晶型，采用粉末X射線衍射分析（PXRD）和差示掃描量熱分析（DSC）對其進(jìn)行表征，并對其進(jìn)行加速穩(wěn)定性試驗和溶劑殘留檢測。結(jié)果 目標(biāo)化合物的收率最高為89%，得到3種不同的晶型A、B和C，穩(wěn)定性、溶劑殘留和鈀殘留均優(yōu)于化合物專利無定型產(chǎn)品。結(jié)論 設(shè)計了一種TJ1508的簡易合成路線，得到3種穩(wěn)定的晶型，其中晶型C最為穩(wěn)定。

Objective To study the synthetic technology of a novel oxazolidinone antibiotic ((3R,3aS)-7-(6-((S)3-methyl-2-oxazolidino-5-yl) pyridin-3-yl)-1-oxo-1,3,3a,4-tetrahydrobenzo[b]oxazolo[3,4-d] [1,4]oxazin-3-yl)methyl)phpsphate (TJ1508), and study its crystal form. Methods TJ1508 was synthesized from dibenzyl phosphate intermediate by acid-catalyzed de-protection. Crystal forms were obtained from different solvent systems and characterized by powder X-ray diffraction (PXRD) and differential scanning calorimeter (DSC). Accelerated stability test and residual solvent analysis were also performed. Results The best yield was 89%, and crystal form A, B and C were obtained from different solvent systems. According to stability test, residual solvent and palladium residue analysis, three crystal forms were superior to amorphous one described in product patent. Conclusion A facile synthetic route for synthesis of TJ1508 is developed. Three stable crystal forms are obtained, and crystal form C is the most stable polymorph.