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【结 构 式】 
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【分子编号】30206 【品名】2,6-dichlorobenzonitrile；2-chloro-6-iodobenzonitrile；Dichlobenil 【CA登记号】1194-65-6 |
【 分 子 式 】C7H3Cl2N 【 分 子 量 】172.01296 【元素组成】C 48.88% H 1.76% Cl 41.22% N 8.14% |
合成路线1
该中间体在本合成路线中的序号：(II)The condensation of 2-methylpyridine (I) with 2,6-dichlorobenzonitrile (II) by means of BuLi and diisopropylamine in THF gives the vinyl derivative (III), which is cyclized by heating at 200 C.
| 【1】 Mettey, Y.; Vierfond, J.-M.; Benzo[c]quinoliziums: A new family of inhibitors for protein kinase CK II. Bioorg Med Chem Lett 1997, 7, 8, 961. |
| 【2】 Becq, F.; Mettey, Y.; Vierfond, J.-M.; Verrier, B.; Gola, M. (CNRS (Centre National de la Recherche Scientifique)); CFTR channel activator cpds. and pharmaceutical compsns. containing same. EP 0937044; WO 9805642 . |
合成路线2
该中间体在本合成路线中的序号：(VI)Condensation of 4-aminophenylboronic acid pinacol ester (I) with 2-fluoro-5-methylphenyl isocyanate (II) in CH2Cl2 provides urea (III) , which is then subjected to Suzuki coupling with either 3-amino-4-iodoindazole (IVa) or 3-amino-4-chloroindazole (IVb) in the presence of Na2CO3 and Pd(PPh3)4 at 160 °C or Pd(dppf)Cl2·CH2Cl2 complex in dimethoxyethane/H2O or K3PO4, Pd(OAc)2 and 1,1’-bis(di-tert-butylphosphino)ferrocene (DBPF) in H2O/EtOH at 55 °C .
The aminoindazoles (IVa) and (IVb) are prepared by cyclization of 2-fluoro-6-iodobenzonitrile (V) or 2-chloro-6-iodobenzonitrile (VI) , respectively, with hydrazine hydrate and, optionally, NaOAc in boiling butanol or pyridine .
| 【1】 Davidsen, S.K., Hartandi, K., Ji, Z., Dai, Y., Ericsson, A.M., Michaelides, M.R. (Abbott Laboratories Inc.). Indazole, benzisoxazole, and benzisothiazole kinase inhibitors. EP 1638941, JP 2007500226, US 2004235892, US 2005020603, WO 2004113304. |
| 【2】 Dai, Y., Hartandi, K., Ji, Z. et al. Discovery of N-(4-(3-amino-1H-indazol-4-yl)phenyl)-N’-(2-fluoro-5-methylphenyl)urea (ABT-869), a 3-aminoindazole-based orally active multitargeted receptor. J Med Chem 2007, 50(7): 1584-97. |
| 【3】 Kruger, A.W., Rozema, M.J., Chu-Kung, A. et al. The discovery and development of a safe, practical synthesis of ABT-869. Org Process Res Dev 2009, 13(6): 1419. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IVa) | 69024 | 3-amino-4-iodoindazole;4-iodo-1H-indazol-3-amine;4-Iodo-1H-indazol-3-ylamine;3-Amino-4-iodo-1H-indazole | 599191-73-8 | C7H6IN3 | 详情 | 详情 |
| (IVb) | 69025 | 3-amino-4-chloroindazole;3-Amino-4-chloro-1H-indazole;4-CHLORO-1H-INDAZOL-3-YLAMINE;4-CHLORO-1H-INDAZOL-3-AMINE | 20925-60-4 | C7H6ClN3 | 详情 | 详情 |
| (I) | 69021 | 4-aminophenylboronic acid pinacol ester;4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)aniline | 214360-73-3 | C12H18BNO2 | 详情 | 详情 |
| (II) | 69022 | 2-fluoro-5-methylphenyl isocyanate;1-Fluoro-2-isocyanato-4-methylbenzene | C8H6FNO | 详情 | 详情 | |
| (III) | 69023 | 1-(2-fluoro-5-methylphenyl)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea | C20H24BFN2O3 | 详情 | 详情 | |
| (V) | 69026 | 2-fluoro-6-iodobenzonitrile;6-Fluoro-2-iodobenzonitrile | 79544-29-9 | C7H3FIN | 详情 | 详情 |
| (VI) | 30206 | 2,6-dichlorobenzonitrile；2-chloro-6-iodobenzonitrile；Dichlobenil | 1194-65-6 | C7H3Cl2N | 详情 | 详情 |