(2-Methoxy-5-(methoxycarbonyl)phenyl)boronic acid → HCID 89783141, compound

HRID 58090Notes

Reaction equation

HRID 58090 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]([C:23]([O:25][CH3:26])=[O:24])=[CH:19][C:18]=1B(O)O>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:22]=[CH:21][C:20]([C:23]([O:25][CH3:26])=[O:24])=[CH:19][C:18]=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

6

Reactant 2

HCID 9837205(2-Methoxy-5-(methoxycarbonyl)phenyl)boronic acidHCID 247292324-Bromo-6-(trifluoromethyl)-1H-indazole

Product 1

HCID 89783141HCID 89783141, compoundYield 71%

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

A vial was charged with a mixture of 4-bromo-6-(trifluoromethyl)-1H-indazole (0.631 g, 2.381 mmol), (2-methoxy-5-(methoxycarbonyl)phenyl)boronic acid (0.5 g, 2.381 mmol) and PdCl2(dppf) (0.087 g, 0.119 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 and the crude residue was diluted with DCM and washed with water, concentrated, and then purified by CombiFlash® chromatography, eluting with a gradient of 0-40% MeOH in DCM over a period of 200 minutes. The product-containing fractions were combined and concentrated to give the title compound as a light brown solid (0.592 g, 71.0%). 1H NMR (400 MHz, DMSO-d6) δ ppm 3.85 (s, 3H), 3.84 (s, 3H), 7.21-7.46 (m, 2H), 7.89-7.99 (m, 3H), 8.10 (dd, J=8.59, 2.27 Hz, 1H), 13.62 (s, 1H); ESI-MS m/z [M+H]+ calc'd for C17H13F3N2O3, 351.1. found 351.16.

Workup

  1. concentrationThe reaction mixture was subsequently concentrated
  2. additionthe crude residue was diluted with DCM
  3. washwashed with water
  4. concentrationconcentrated
  5. custompurified by CombiFlash® chromatography
  6. washeluting with a gradient of 0-40% MeOH in DCM over a period of 200 minutes
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-a658effd689340768dcf14bb48c285d6
Source dataset
uspto-grants-2016_09
Patent number
US09434743B2

Reaction notes

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