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

반응식

HRID 58057 반응식
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

참가 물질

6

반응물 2

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

생성물 1

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

시약·촉매·용매 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 312751,4-Dioxane용매HCID 516892Sodium Bicarbonate용매

반응 조건

온도
140 °C

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-7b4696d4a09f4195b0840b9023d9c9c9
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09434743B2

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