|
【结 构 式】 
|
【药物名称】L-168721 【化学名称】N-(6-Aminohexyl)-2-[6-phenyl-2-(2-phenylethyl)-4-oxo-3,4-dihydro-3-quinazolinyl]acetamide hydrochloride 【CA登记号】 【 分 子 式 】C30H35ClN4O2 【 分 子 量 】519.09205 |
【开发单位】Merck & Co. (Originator) 【药理作用】ENDOCRINE DRUGS, Pituitary Disorder Therapy, Treatment of Growth Hormone Secretion Disorders, Growth Hormone Secretagogues |
合成路线1
The cyclization of 2-amino-5-bromobenzoic acid (I) with 3-phenylpropionyl chloride (II) by means of DMAP and Et3N in DMF gives the benzoxazinone (III), which by heating with glycine methyl ester (IV) yields the quinazolinone (V). The hydrolysis if (V) with NaOH in THF/water affords 2-[6-bromo-4-oxo-2-(2-phenylethyl)-3,4-dihydroquinazolin-3-yl]acetic acid (VI), which is condensed with the monoprotected hexane-1,6-diamine (VII), by means of HOBt, EDC and NMM to provide the amide (VIII). The condensation of (VIII) with phenylboronic acid (IX) by means of palladium tetrakis(triphenylphosphoine) gives the 6-phenyl substituted quinazolinone (X), which is finally deprotected with HCl.
| 【1】 Ye, Z.; Bakshi, R.K.; Gao, Y.; et al.; Modeling directed design and biological evaluation of quinazolinones as non-peptidic growth hormone secretagogues. Bioorg Med Chem Lett 2000, 10, 1, 5. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 16593 | Phenylboronic acid；Benzeneboronic acid;Phenylboron dihydroxide | 98-80-6 | C6H7BO2 | 详情 | 详情 |
| (I) | 31634 | 2-amino-5-bromobenzoic acid | 5794-88-7 | C7H6BrNO2 | 详情 | 详情 |
| (II) | 16240 | 3-phenylpropanoyl chloride; Hydrocinnamoylchloride | 645-45-4 | C9H9ClO | 详情 | 详情 |
| (III) | 31635 | 6-bromo-2-phenethyl-4H-3,1-benzoxazin-4-one | C16H12BrNO2 | 详情 | 详情 | |
| (IV) | 17568 | methyl 2-aminoacetate | C3H7NO2 | 详情 | 详情 | |
| (V) | 31636 | methyl 2-[6-bromo-4-oxo-2-phenethyl-3(4H)-quinazolinyl]acetate | C19H17BrN2O3 | 详情 | 详情 | |
| (VI) | 31637 | 2-[6-bromo-4-oxo-2-phenethyl-3(4H)-quinazolinyl]acetic acid | C18H15BrN2O3 | 详情 | 详情 | |
| (VII) | 31638 | tert-butyl 6-aminohexylcarbamate | 51857-17-1 | C11H24N2O2 | 详情 | 详情 |
| (VIII) | 31639 | tert-butyl 6-([2-[6-bromo-4-oxo-2-phenethyl-3(4H)-quinazolinyl]acetyl]amino)hexylcarbamate | C29H37BrN4O4 | 详情 | 详情 | |
| (IX) | 31640 | tert-butyl 6-([2-[4-oxo-2-phenethyl-6-phenyl-3(4H)-quinazolinyl]acetyl]amino)hexylcarbamate | C35H42N4O4 | 详情 | 详情 |