4-Bromo-6-(trifluoromethyl)-1H-indazole → methyl 2-(4-methoxy-3-(6-(trifluoromethyl)-1H-indazol-4-yl)phenyl)acetate

HRID 58063

Reaction equation

Br[C:2]1[CH:10]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:8]=[C:7]2[C:3]=1[CH:4]=[N:5][NH:6]2.[CH3:15][O:16][C:17]1[CH:22]=[CH:21][C:20]([CH2:23][C:24]([O:26][CH3:27])=[O:25])=[CH:19][C:18]=1B1OC(C)(C)C(C)(C)O1>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]>[CH3:15][O:16][C:17]1[CH:18]=[CH:19][C:20]([CH2:23][C:24]([O:26][CH3:27])=[O:25])=[CH:21][C:22]=1[C:2]1[CH:10]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:8]=[C:7]2[C:3]=1[CH:4]=[N:5][NH:6]2

Participants

Conditions

Temperature: 140 °C

Procedure

A vial was charged with a mixture of 4-bromo-6-(trifluoromethyl)-1H-indazole (0.433 g, 1.633 mmol), methyl 2-(4-methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acetate (0.5 g, 1.633 mmol) and PdCl2(dppf) (0.060 g, 0.082 mmol) in dioxane (10 mL) and aqueous saturated NaHCO3 (3 mL). The resulting light brown suspension was heated at 140° C. for 45 minutes in a microwave reactor. The reaction mixture was subsequently concentrated. The crude residue was dissolved in EtOAc and was washed with water and brine, concentrated, and purified by CombiFlash® chromatography (0-35% MeOH in DCM). The product-containing fractions were combined and concentrated by rotary evaporation to give the title compound (0.47 g, 79%). ESI-MS m/z [M+H]+ calc'd for C18H15F3N2O3, 365.1. found 365.2.

Workup

concentrationThe reaction mixture was subsequently concentrated
dissolutionThe crude residue was dissolved in EtOAc
washwas washed with water and brine
concentrationconcentrated
custompurified by CombiFlash® chromatography (0-35% MeOH in DCM)
concentrationconcentrated by rotary evaporation

Sources & evidence

ORD record: ord-edf0eb21465345309be40b2e3200d4f8
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09434743B2

Linked notes

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