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【结 构 式】

【药物名称】CT-5276-00, CT-5276

【化学名称】N-[4-[2-(Diethylamino)ethoxy]-3,5-dimethoxyphenyl]-9-methoxy-6,6-dimethyl-5,6-dihydrobenzo[h]quinazolin-2-amine

【CA登记号】209740-42-1

【 分 子 式 】C29H38N4O4

【 分 子 量 】506.65061

【开发单位】Celltech (Originator)

【药理作用】IMMUNOMODULATING AGENTS, Immunomodulators, Src Kinase Inhibitors

合成路线1

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 the chloroquinazoline (IX) using phosphoryl chloride and DMF. Aniline (XIII) was obtained by alkylation of 2,6-dimethoxy-4-nitrophenol (X) with (diethylamino)ethyl chloride (XI) in the presence of Cs2CO3 to give (XII), followed by catalytic transfer hydrogenation of the nitro group of (XII) with ammonium formate and Pd/C. Finally, condensation of chloroquinazoline (IX) with aniline (XIII) in refluxing ethoxyethanol yielded 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) 23778 2,6-dimethoxy-4-nitrophenol C8H9NO5 详情 详情
(XI) 16194 2-chloro-N,N-diethyl-1-ethanamine; N-(2-chloroethyl)-N,N-diethylamine 100-35-6 C6H14ClN 详情 详情
(XII) 23779 N-[2-(2,6-dimethoxy-4-nitrophenoxy)ethyl]-N,N-diethylamine; 2-(2,6-dimethoxy-4-nitrophenoxy)-N,N-diethyl-1-ethanamine C14H22N2O5 详情 详情
(XIII) 23780 4-[2-(diethylamino)ethoxy]-3,5-dimethoxyaniline; N-[2-(4-amino-2,6-dimethoxyphenoxy)ethyl]-N,N-diethylamine C14H24N2O3 详情 详情
Extended Information