• English
  • 简体中文
Login Register
Current Location: Home > Feedback Help Print

【结 构 式】

【分子编号】65077

【品名】N-(8-amino-4,4-dimethyl-1,3-dioxo-1,2,3,4-tetrahydro-7-isoquinolinyl)-N'-(2,6-dichlorophenyl)thiourea

【CA登记号】

【 分 子 式 】C18H16Cl2N4O2S

【 分 子 量 】423.3222

【元素组成】C 51.07% H 3.81% Cl 16.75% N 13.24% O 7.56% S 7.57%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(XI)

Alkylation of (2-cyanophenyl)acetonitrile (I) with iodomethane under phase-transfer conditions leads to the alpha,alpha-dimethyl nitrile (II), which is further cyclized to imide (III) with 90% H2SO4. Subsequent nitration of homophthalimide (III) with HNO3/H2SO4 furnishes (IV) (1). Nitrophthalimide (IV) is reduced to the corresponding amine (V) by hydrogenation in the presence of Pd/C. This is then converted into acetamide (VI) by treatment with Ac2O. A second nitration reaction with cold HNO3 leads to the nitro amide (VII), which is further hydrolyzed with H2SO4 to the nitro amine (VIII). Hydrogenation of (VIII) over PtO2 furnishes diamine (IX). Coupling of (IX) with 2,6-dichlorophenyl isothiocyanate (X) gives thiourea (XI). Ring closure of amino thiourea (XI) to the benzimidazole derivative (XII) is carried out by treatment with DCC in refluxing THF. Partial reduction of the imide function of (XII) with NaBH4 in moist THF affords (XIII). Finally, rearrangement of (XIII) in concentrated H2SO4 at room temperature gives rise to the title compound (1,2).

1 Snow, R.J.; Cardozo, M.G.; Morwick, T.M.; Bussacca, C.A.; Dong, Y.; Eckner, R.J.; Jacober, S.; Jakes, S.; Kapadia, S.; Lukas, S.; Panzenbeck, M.; Peet, G.W.; Peterson, J.D.; Prokopowicz, A.S. III; Sellati, R.; Tolbert, R.M.; Tschantz, M.A.; Moss, N.; Discovery of 2-phenylamino-imidazo[4,5-h]isoquinolin-9-ones: A new class of inhibitors of lck kinase. J Med Chem 2002, 45, 16, 3394.
2 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) 21593 2-(cyanomethyl)benzonitrile 3759-28-2 C9H6N2 详情 详情
(II) 65069 2-(1-cyano-1-methylethyl)benzonitrile C11H10N2 详情 详情
(III) 21594 4,4-dimethyl-1,3(2H,4H)-isoquinolinedione C11H11NO2 详情 详情
(IV) 65072 4,4-dimethyl-7-nitro-1,3(2H,4H)-isoquinolinedione C11H10N2O4 详情 详情
(V) 65071 7-amino-4,4-dimethyl-1,3(2H,4H)-isoquinolinedione C11H12N2O2 详情 详情
(VI) 65070 N-(4,4-dimethyl-1,3-dioxo-1,2,3,4-tetrahydro-7-isoquinolinyl)acetamide C13H14N2O3 详情 详情
(VII) 65073 N-(4,4-dimethyl-8-nitro-1,3-dioxo-1,2,3,4-tetrahydro-7-isoquinolinyl)acetamide C13H13N3O5 详情 详情
(VIII) 65074 7-amino-4,4-dimethyl-8-nitro-1,3(2H,4H)-isoquinolinedione C11H11N3O4 详情 详情
(IX) 65075 7,8-diamino-4,4-dimethyl-1,3(2H,4H)-isoquinolinedione C11H13N3O2 详情 详情
(X) 52344 2,6-Dichlorophenyl isothiocyanate 6590-95-0 C7H3Cl2NS 详情 详情
(XI) 65077 N-(8-amino-4,4-dimethyl-1,3-dioxo-1,2,3,4-tetrahydro-7-isoquinolinyl)-N'-(2,6-dichlorophenyl)thiourea C18H16Cl2N4O2S 详情 详情
(XII) 65076 2-(2,6-dichloroanilino)-6,6-dimethyl-1H-imidazo[4,5-h]isoquinoline-7,9(6H,8H)-dione C18H14Cl2N4O2 详情 详情
(XIII) 65078 2-(2,6-dichloroanilino)-7-hydroxy-6,6-dimethyl-1,6,7,8-tetrahydro-9H-imidazo[4,5-h]isoquinolin-9-one C18H16Cl2N4O2 详情 详情
Extended Information