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 58057Notes

Reaction equation

HRID 58057 reaction equation
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

Participants

6

Reactant 2

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

Product 1

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

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
140 °C

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-7b4696d4a09f4195b0840b9023d9c9c9
Source dataset
uspto-grants-2016_09
Patent number
US09434743B2

Reaction notes

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