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【结 构 式】 
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【分子编号】67741 【品名】(4aR,11aS,12aR,13R)-3,7-bis(benzyloxy)-8-(dibenzylamino)-13-(dimethylamino)-10-fluoro-4a,5-dihydroxy-11a,12,12a,13-tetrahydrotetraceno[2,3-d]isoxazole-4,6(4aH,11H)-dione 【CA登记号】 |
【 分 子 式 】C49H44FN3O7 【 分 子 量 】805.903 【元素组成】C 73.03% H 5.50% F 2.36% N 5.21% O 13.90% |
合成路线1
该中间体在本合成路线中的序号：(XVIII)The tandem Michael-Dieckmann reaction of toluate ester (XVI) with the tricyclicenone (VI) using LDA and LiHMDS in THF yields the pentacyclic compound (XVII) , which by desilylation with HF in acetonitrile provide sdiol (XVIII). Subsequenthy drogenolysis of isoxazole derivative (XVIII) in the presence of Pd/Cand HCl in MeOH/THF affords 9-amino-7-fluorosancycline (XI),which is finally acylated with pyrrolidin-1-ylacetylchloride (XV)[prepared by chlorination of pyrrolidin-1-ylaceticacid (VII) with (COCl)2 in CH2Cl2] in acetonitrile/H2O .
| 【1】 Ronn,M.,Zhu, Z. J.,Hogan, P. C.etal.Process R&D of evaracycline: The first synthetic fluorocycline in clinical development. Org Process Res Dev 2013, 17: 838. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VI) | 67730 | (4aR,8aR,9R)-3-(benzyloxy)-4a-((tert- butyldimethylsilyl)oxy)-9-(dimethylamino)-8,8a,9,9a- tetrahydronaphtho[2,3-d]isoxazole-4,5(3aH,4aH)-dione | C26H34N2O5Si | 详情 | 详情 | |
| (XI) | 67735 | (4R,4aR,5aS,12aR)-9-amino-4-(dimethylamino)-7-fluoro-3,10,12,12a-tetrahydroxy-1,11-dioxo-1,2,3,4,4a,5,5a,6,11,12a-decahydrotetracene-2-carboxamide | C21H24FN3O7 | 详情 | 详情 | |
| (XV) | 67737 | 2-(pyrrolidin-1-yl)acetyl chloride | C6H10ClNO | 详情 | 详情 | |
| (XVI) | 67738 | phenyl 2-(benzyloxy)-3-(dibenzylamino)-5-fluoro-6-methylbenzoate | C35H30FNO3 | 详情 | 详情 | |
| (XVII) | 67740 | (4aR,11aS,12aR,13R)-3,7-bis(benzyloxy)-4a-((tert-butyldimethylsilyl)oxy)-8-(dibenzylamino)-13-(dimethylamino)-10-fluoro-5-hydroxy-11a,12,12a,13-tetrahydrotetraceno[2,3-d]isoxazole-4,6(4aH,11H)-dione | C55H58FN3O7Si | 详情 | 详情 | |
| (XVIII) | 67741 | (4aR,11aS,12aR,13R)-3,7-bis(benzyloxy)-8-(dibenzylamino)-13-(dimethylamino)-10-fluoro-4a,5-dihydroxy-11a,12,12a,13-tetrahydrotetraceno[2,3-d]isoxazole-4,6(4aH,11H)-dione | C49H44FN3O7 | 详情 | 详情 | |
| (XIX) | 67739 | 2-(pyrrolidin-1-yl)acetic acid hydrochloride | C6H11NO2.HCl | 详情 | 详情 |