【结 构 式】 |
【分子编号】65080 【品名】ethyl 2-(3-amino-2-cyano-4-nitrophenyl)-2-methyl-3-oxobutanoate 【CA登记号】 |
【 分 子 式 】C14H15N3O5 【 分 子 量 】305.29032 【元素组成】C 55.08% H 4.95% N 13.76% O 26.2% |
合成路线1
该中间体在本合成路线中的序号:(IV)In an alternative method, 2,6-dichloro-3-nitrobenzonitrile (I) is heated with ethanolic ammonia in a sealed vessel to produce the 2-amino benzonitrile (II). Subsequent condensation of 2-amino-6-chloro-3-nitrobenzonitrile (II) with ethyl methylacetoacetate (III) in the presence of K2CO3 leads to the aryl methyl acetoacetate ester (IV). Decarboxylation and cyclization of (IV) under acidic conditions then produces isoquinolinone (V). Nitro group reduction in (V) with H2 and Pd/C leads to diamine (VI), which is further coupled with 2,6-dichlorophenyl isothiocyanate (VII), yielding thiourea (VIII). Finally, ring closure of amino thiourea (VIII) with DCC in hot DMF affords the target tricyclic compound (2).
【1】 Goldberg, D.; Cardozo, M.G.; Tschantz, M.A.; Moss, N.; Morwick, T.; Prokopowicz, A.S. III; Snow, R.J.; Patel, U.R.; Wang, X.-J.; Hammach, A.; Takahashi, H. (Boehringer Ingelheim Pharmaceuticals Inc.); Heterocyclic cpds. useful as inhibitors of tyrosine kinases. WO 0125238 . |
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) | 52340 | 2,6-Dichloro-3-nitrobenzonitrile | 5866-98-8 | C7H2Cl2N2O2 | 详情 | 详情 |
(II) | 65079 | 2-amino-6-chloro-3-nitrobenzonitrile | C7H4ClN3O2 | 详情 | 详情 | |
(III) | 10362 | ethyl 2-methyl-3-oxobutanoate; ethyl 2-methylacetoacetate | 609-14-3 | C7H12O3 | 详情 | 详情 |
(IV) | 65080 | ethyl 2-(3-amino-2-cyano-4-nitrophenyl)-2-methyl-3-oxobutanoate | C14H15N3O5 | 详情 | 详情 | |
(V) | 65082 | 8-amino-3,4-dimethyl-7-nitro-1(2H)-isoquinolinone | C11H11N3O3 | 详情 | 详情 | |
(VI) | 65081 | 7,8-diamino-3,4-dimethyl-1(2H)-isoquinolinone | C11H13N3O | 详情 | 详情 | |
(VII) | 52344 | 2,6-Dichlorophenyl isothiocyanate | 6590-95-0 | C7H3Cl2NS | 详情 | 详情 |
(VIII) | 65083 | N-(8-amino-3,4-dimethyl-1-oxo-1,2-dihydro-7-isoquinolinyl)-N'-(2,6-dichlorophenyl)thiourea | C18H16Cl2N4OS | 详情 | 详情 |