Methyl 3-bromoimidazo[1,2-b]pyridazine-6-carboxylate → 3-(6-(trifluoromethyl)-1H-indazol-4-yl)imidazo[1,2-b]pyridazine-6-carboxylic acid

HRID 58057

反応式

HRID 58057 の反応式
CC1(C)C(C)(C)OB([C:9]2[CH:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:15]=[C:14]3[C:10]=2[CH:11]=[N:12][NH:13]3)O1.Br[C:24]1[N:28]2[N:29]=[C:30]([C:33]([O:35]C)=[O:34])[CH:31]=[CH:32][C:27]2=[N:26][CH:25]=1>O1CCOCC1.C([O-])(O)=O.[Na+].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:21][C:18]([F:19])([F:20])[C:16]1[CH:15]=[C:14]2[C:10]([CH:11]=[N:12][NH:13]2)=[C:9]([C:24]2[N:28]3[N:29]=[C:30]([C:33]([OH:35])=[O:34])[CH:31]=[CH:32][C:27]3=[N:26][CH:25]=2)[CH:17]=1

参加物

6

反応物 2

HCID 72207465Methyl 3-bromoimidazo[1,2-b]pyridazine-6-carboxylateHCID 897828064-(Tetramethyl-1,3,2-dioxaborolan-2-yl)-6-(trifluoromethyl)-1H-indazole

生成物 1

HCID 897828553-(6-(trifluoromethyl)-1H-indazol-4-yl)imidazo[1,2-b]pyridazine-6-carboxylic acid

試薬・触媒・溶媒 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 312751,4-Dioxane溶媒HCID 516892Sodium Bicarbonate溶媒

反応条件

温度
140 °C

実験手順

To a 10 mL vial was added a mixture of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-6-(trifluoromethyl)-1H-indazole (0.066 g, 0.211 mmol), methyl 3-bromoimidazo[1,2-b]pyridazine-6-carboxylate (0.054 g, 0.211 mmol) and PdCl2(dppf) (7.74 mg, 10.57 μmol) in dioxane (2 mL) and aqueous saturated NaHCO3 (1 mL). The resulting orange suspension was heated at 140° C. for 30 minutes in a microwave reactor. The major peak by LCMS was the decarboxylated product. The reaction mixture was extracted into EtOAc and the water layer was separated and acidified with concentrated HCl to pH 2. The water layer was extracted with EtOAc. The organic layers were combined, dried over Na2SO4, filtered, and concentrated to give an oil, which was used without further purification (36 mg).

後処理

  1. additionTo a 10 mL vial was added
  2. extractionThe reaction mixture was extracted into EtOAc
  3. customthe water layer was separated
  4. extractionThe water layer was extracted with EtOAc
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give an oil, which
  9. customwas used without further purification (36 mg)

出典と根拠

ORDレコード
ord-7b4696d4a09f4195b0840b9023d9c9c9
出典データセット
uspto-grants-2016_09
特許番号
US09434743B2

関連ノート

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