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【结 构 式】 
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【分子编号】23776 【品名】2,3-dimethoxy-5-[(9-methoxy-6,6-dimethyl-5,6-dihydrobenzo[h]quinazolin-2-yl)amino]phenol 【CA登记号】 |
【 分 子 式 】C23H25N3O4 【 分 子 量 】407.46932 【元素组成】C 67.8% H 6.18% N 10.31% O 15.71% |
合成路线1
该中间体在本合成路线中的序号：(XI)Condensation of anisole (I) with gamma,gamma-dimethylbutyrolactone (II) in the presence of AlCl3 in 1-nitropropane gave 4-(4-methoxyphenyl)-4-methylpentanoic acid (III), which was cyclized to the tetralone (V) using polyphosphoric acid. Subsequent treatment of (V) with refluxing N,N-dimethylformamide dimethyl acetal provided the dimethylamino-methylene compound (VI). This was cyclized with guanidinium carbonate in boiling isopropanol to furnish the benzoquinazoline (VII). Then, diazotization of (VII) in aqueous sulfuric acid generated the quinazolinone (VIII), which was subsequently converted to chloroquinazoline (IX) with phosphoryl chloride in the presence of DMF. Condensation of (IX) with aniline (X) in refluxing ethoxyethanol gave (XI). Finally, the hydroxyl group of (XI) was alkylated with (diethylamino)ethyl chloride (XII) in the presence of Cs2CO3 in DMF at 110 C to yield the title compound.
| 【1】 Davis, J.M.; Hutchings, M.C.; Moffat, D.; Batchelor, M.; Parry, D.M.; Johnson, J.; Berg, D.A.; Davis, P.D.; Benzo[h]-5,6-dihydroquinazoline-2-amines as potent. 15th European Federation for Medicinal Chemistry International Symposium on Medicinal Chemistry (Sept 6 1998, Edinburgh) 1998, Abst P.234. |
| 【2】 Moffat, D.F.C.; Davis, J.M.; Batchelor, M.J.; Davis, P.D. (Celltech Chiroscience plc); Fused polycyclic 2-aminopyrimidine derivs., their . EP 0946523; US 6057329; WO 9828281 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 23767 | Methoxybenzene; Methyl phenyl ether; Anisole | 100-66-3 | C7H8O | 详情 | 详情 |
| (II) | 23768 | 5,5-dimethyldihydro-2(3H)-furanone | C6H10O2 | 详情 | 详情 | |
| (III) | 23769 | 4-(4-methoxyphenyl)-4-methylpentanoic acid | 23203-48-7 | C13H18O3 | 详情 | 详情 |
| (V) | 23770 | 7-methoxy-4,4-dimethyl-3,4-dihydro-1(2H)-naphthalenone | C13H16O2 | 详情 | 详情 | |
| (VI) | 23771 | 2-[(E)-(dimethylamino)methylidene]-7-methoxy-4,4-dimethyl-3,4-dihydro-1(2H)-naphthalenone | C16H21NO2 | 详情 | 详情 | |
| (VII) | 23772 | 9-methoxy-6,6-dimethyl-5,6-dihydrobenzo[h]quinazolin-2-ylamine; 9-methoxy-6,6-dimethyl-5,6-dihydrobenzo[h]quinazolin-2-amine | C15H17N3O | 详情 | 详情 | |
| (VIII) | 23773 | 9-methoxy-6,6-dimethyl-5,6-dihydrobenzo[h]quinazolin-2(1H)-one | C15H16N2O2 | 详情 | 详情 | |
| (IX) | 23774 | 2-chloro-6,6-dimethyl-5,6-dihydrobenzo[h]quinazolin-9-yl methyl ether; 2-chloro-9-methoxy-6,6-dimethyl-5,6-dihydrobenzo[h]quinazoline | C15H15ClN2O | 详情 | 详情 | |
| (X) | 23775 | 5-amino-2,3-dimethoxyphenol | C8H11NO3 | 详情 | 详情 | |
| (XI) | 23776 | 2,3-dimethoxy-5-[(9-methoxy-6,6-dimethyl-5,6-dihydrobenzo[h]quinazolin-2-yl)amino]phenol | C23H25N3O4 | 详情 | 详情 | |
| (XII) | 16194 | 2-chloro-N,N-diethyl-1-ethanamine; N-(2-chloroethyl)-N,N-diethylamine | 100-35-6 | C6H14ClN | 详情 | 详情 |