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【结 构 式】 
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【分子编号】68538 【品名】(R)-methyl 2-(isopropylamino)butanoate hydrochloride;methyl (R)-2-isopropylamino)butyrate hydrochloride 【CA登记号】 |
【 分 子 式 】C8H17NO2.HCl 【 分 子 量 】195.689 【元素组成】C 48.10% H 9.27% Cl 18.12% N 7.16% O 16.35% |
合成路线1
该中间体在本合成路线中的序号：(XIII)Esterification of (R)-2-aminobutyric acid (X) with MeOH by means of SOCl2 and trimethyl orthoformate, followed by reductive alkylation of the resulting amino ester (XI) with acetone (XII) and NaBH(OAc)3, and treatment with HCl, gives methyl (R)-2-isopropylamino)butyrate hydrochloride (XIII). Basification of amino ester hydrochloride (XIII) with NaOH in cyclohexane/H2O, and subsequent condensation of the obtained free base with 2,4-dichloro-5-nitropyrimidine (XIV) in the presence of NaHCO3 in refluxing cyclohexane, yields the Npyrimidinyl amino ester (XV). Reductive cyclization of compound (XV) by catalytic hydrogenation in the presence of Pt/C and VO(acac)2 in THF gives pteridinone (XVI), which is finally methylated by heating with Me2CO3 in an autoclave in the presence of K2CO3 .
| 【1】 Grauert, M., Linz, G., Schmid, R., Sieger, P. (Boehringer Ingelheim Pharma GmbH & Co. KG). Trihydrochloride forms of a dihydropteridinone derivative and process for preparation. WO 2007090844. |
| 【2】 Linz, G., Sieger, P., Schmid, R., Goepper, S. (Boehringer International GmbH). Crystalline form of a dihydropteridinone derivative. WO 2009019205. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IX) | 68535 | (R)-2-chloro-7-ethyl-8-isopropyl-5-methyl-7,8-dihydropteridin-6(5H)-one | C12H17ClN4O | 详情 | 详情 | |
| (X) | 68536 | (R)-2-aminobutyric acid | C4H9NO2 | 详情 | 详情 | |
| (XI) | 68537 | (R)-methyl 2-aminobutanoate hydrochloride | C4H9NO2.HCl | 详情 | 详情 | |
| (XII) | 53313 | acetone | 67-64-1 | C3H6O | 详情 | 详情 |
| (XIII) | 68538 | (R)-methyl 2-(isopropylamino)butanoate hydrochloride;methyl (R)-2-isopropylamino)butyrate hydrochloride | C8H17NO2.HCl | 详情 | 详情 | |
| (XIV) | 68539 | 2,4-dichloro-5-nitropyrimidine | 49845-33-2 | C4HCl2N3O2 | 详情 | 详情 |
| (XV) | 68540 | (R)-methyl 2-((2-chloro-5-nitropyrimidin-4-yl)(isopropyl)amino)butanoate | C12H17ClN4O4 | 详情 | 详情 | |
| (XVI) | 68541 | (R)-2-chloro-7-ethyl-8-isopropyl-7,8-dihydropteridin-6(5H)-one | C11H15ClN4O | 详情 | 详情 |