Hydrochloric Acid → N-(2'-Fluoro-5-methyl-3-nitro-biphenyl-4-yl)-hydroxylamine

HRID 644934ノート

反応式

HRID 644934 の反応式
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:13]=[C:12]([CH3:14])[C:11]([NH2:15])=[C:10]([N+:16]([O-:18])=[O:17])[CH:9]=1.N([O-])=[O:20].[Na+].Cl>C(O)(=O)C>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:13]=[C:12]([CH3:14])[C:11]([NH:15][OH:20])=[C:10]([N+:16]([O-:18])=[O:17])[CH:9]=1

参加物

5

反応物 3

HCID 313Hydrochloric AcidHCID 23668193Sodium NitriteHCID 592637522'-Fluoro-5-methyl-3-nitro-biphenyl-4-ylamine

生成物 1

HCID 59263751N-(2'-Fluoro-5-methyl-3-nitro-biphenyl-4-yl)-hydroxylamine

試薬・触媒・溶媒 1

HCID 176Acetic Acid溶媒

実験手順

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

後処理

  1. customOne reaction

出典と根拠

ORDレコード
ord-4c395e68d33c48dfa0976da4ba8c5e7e
出典データセット
uspto-grants-2010_04
特許番号
US07700773B2

反応ノート

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