Reaction #732116
ord-4c395e68d33c48dfa0976da4ba8c5e7e
Reaction equation
Reactants
Reagents
Solvents
Conditions
Workup
- 1OtherOne reaction
Procedure
Reflux of a combination of starting compounds 4-Bromo-2-methyl-6-nitro-phenylamine 160 and aromatic boronic acid 161 in the presence of Pd(Ph3P)4, K3PO4, Benzene, dimethylformamide gives rise to intermediate 2′-Fluoro-5-methyl-3-nitro-biphenyl-4-ylamine 162. Tricyclic intermediate 5-(2-Fluoro-phenyl)-7-nitro-2H-indazole 165 is formed from intermediate 162 by using one of two reactions. One reaction involves treating intermediate 162 with sodium nitrite, acetic acid, and hydrochloric acid to form intermediate N-(2′-Fluoro-5-methyl-3-nitro-biphenyl-4-yl)-hydroxylamine 163 then refluxing intermediate 163 in benzene to form intermediate 165. The second reaction involves treating intermediate 162 with HBF4 and sodium nitrite forming intermediate 2′-Fluoro-5-methyl-3-nitro-biphenyl-4-diazonium+ BF4− 164 then treating intermediate 164 with potassium acetate and 18-Crown-6 in chloroform to form intermediate 165. Intermediate 165 is treated with Pd—C in ethanol and hydrogen, which reduces the nitro substituent of intermediate 165 to an amine forming intermediate 5-(2-Fluoro-phenyl)-2H-indazol-7-ylamine 166. Treatment of intermediate 166 with Bu4NBr3 (TBATB) and DMF-H2O brominated intermediate 166 to form intermediate 4-Bromo-5-(2-fluoro-phenyl)-2H-indazol-7-ylamine 167. The bromine of intermediate 167 is replaced with a carbonitrile group by refluxing in coppercyanide in pyridine forming intermediate 7-Amino-5-(2-fluoro-phenyl)-2H-indazole-4-carbonitrile 168. Reductive alkylation of intermediate 168 is accomplished by treating intermediate 168 with the appropriate aldehyde in the presence of zinc chloride and sodium cyano borohydride forming intermediate 169, which is brominated by treatment with Bu4NBr3 (TBATB) in DMF-H2O forming target compound 7-Amino-3-bromo-5-(2-fluoro-phenyl)-2H-indazole-4-carbonitrile derivative 170