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【结 构 式】 
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【分子编号】68614 【品名】diethyl 4-oxopyran-2,5-dicarboxylate;diethyl 4-oxo-4H-pyran-2,5-dicarboxylate 【CA登记号】 |
【 分 子 式 】C11H12O6 【 分 子 量 】240.21268 【元素组成】C 55% H 5.04% O 39.96% |
合成路线1
该中间体在本合成路线中的序号：(LIX)Condensation of ethyl 3-oxobutyrate (LVII) with N,N-dimethylformamide dimethylacetal (XXXII) in EtOAc affords ethyl 2-acetyl-3-(dimethylamino)-2-propenoate (LVIII), which by cyclocondensation with ethyl oxalyl chloride (XXI) by means of LiHMDS in THF provides diethyl 4-oxopyran-2,5-dicarboxylate (LIX). Condensation of pyranone derivative (LIX) with 2,2-dimethoxyethylamine (XXVI) in EtOH gives pyridone (LX), which is then brominated with NBS in DMF to yield the 3-bromopyridin-4-one derivative (LXI). Hydrolysis of acetal (LXI) using HCOOH and H2SO4 in CH2Cl2 yields the corresponding aldehyde (LXII), which is cyclized with 3(R)-aminobutan-1-ol (XI) in the presence of AcOH in refluxing MeOH/toluene to afford the hexahydropyrido[1’,2’:4,5]pyrazino[2,1-b][1,3]oxazine derivative (LXIII). Finally, bromo ester (LXIII) is submitted to treatment with KOSiMe3 in DME .
| 【1】 Sumino, Y., Okamoto, K., Masui, M., Yamada, D., Ikarashi, F. (Shionogi & Co., Ltd.). Process for preparing compound having HIV integrase inhibitory activity. WO 2012018065. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XI) | 68577 | 3(R)-amino-1-butanol;(R)-3-aminobutan-1-ol | 61477-39-2 | C4H11NO | 详情 | 详情 |
| (XXI) | 11043 | Ethyl 2-chloro-2-oxoacetate; Ethyl oxalyl chloride | 4755-77-5 | C4H5ClO3 | 详情 | 详情 |
| (XXVI) | 34158 | aminoacetaldehyde dimethylacetal; 2,2-dimethoxy-1-ethanamine; 2,2-dimethoxyethylamine | 22483-09-6 | C4H11NO2 | 详情 | 详情 |
| (XXXII) | 11984 | N-(Dimethoxymethyl)-N,N-dimethylamine;dimethylformamide dimethylacetal;1,1-dimethoxy-N,N-dimethylmethanamine； Dimethoxy-N,N-dimethylmethanamine; N,N-Dimethylformamide dimethyl acetal | 4637-24-5 | C5H13NO2 | 详情 | 详情 |
| (LVI) | 68611 | (4R,12aS)-7-chloro-4-methyl-6,8-dioxo-3,4,6,8,12,12a-hexahydro-2H-pyrido[1',2':4,5]pyrazino[2,1-b][1,3]oxazine-9-carboxylic acid | C13H13ClN2O5 | 详情 | 详情 | |
| (LVII) | 11819 | ethyl acetoacetate; ethyl 3-oxobutanoate；Acetoacetic ester;Ethyl beta-ketobutyrate;ethyl 3-oxobutyrate | 141-97-9 | C6H10O3 | 详情 | 详情 |
| (LVIII) | 68613 | ethyl 2-acetyl-3-(dimethylamino)-2-propenoate;Ethyl 2-acetyl-3-(dimethylamino)acrylate;Ethyl (2E)-2-(dimethylaminomethylidene)-3-oxobutanoate | 51145-57-4 | C9H15NO3 | 详情 | 详情 |
| (LIX) | 68614 | diethyl 4-oxopyran-2,5-dicarboxylate;diethyl 4-oxo-4H-pyran-2,5-dicarboxylate | C11H12O6 | 详情 | 详情 | |
| (LX) | 68615 | diethyl 1-(2,2-dimethoxyethyl)-4-oxo-1,4-dihydropyridine-2,5-dicarboxylate | C15H21NO7 | 详情 | 详情 | |
| (LXI) | 68616 | diethyl 3-bromo-1-(2,2-dimethoxyethyl)-4-oxo-1,4-dihydropyridine-2,5-dicarboxylate | C15H20BrNO7 | 详情 | 详情 | |
| (LXII) | 68617 | diethyl 3-bromo-4-oxo-1-(2-oxoethyl)-1,4-dihydropyridine-2,5-dicarboxylate | C13H14BrNO6 | 详情 | 详情 | |
| (LXIII) | 68618 | (4R,12aS)-ethyl 7-bromo-4-methyl-6,8-dioxo-3,4,6,8,12,12a-hexahydro-2H-pyrido[1',2':4,5]pyrazino[2,1-b][1,3]oxazine-9-carboxylate | C15H17BrN2O5 | 详情 | 详情 |