2-Methoxy-4-methylpyridine-5-boronic acid → HCID 89783103, compound

HRID 58082Notes

Reaction equation

HRID 58082 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[N:22]=[CH:21][C:20](B(O)O)=[C:19]([CH3:26])[CH:18]=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]>[CH3:15][O:16][C:17]1[N:22]=[CH:21][C:20]([C:2]2[CH:10]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:8]=[C:7]3[C:3]=2[CH:4]=[N:5][NH:6]3)=[C:19]([CH3:26])[CH:18]=1

Participants

6

Reactant 2

HCID 27630832-Methoxy-4-methylpyridine-5-boronic acidHCID 247292324-Bromo-6-(trifluoromethyl)-1H-indazole

Product 1

HCID 89783103HCID 89783103, compoundYield 46%

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 (0.1 g, 0.377 mmol), (6-methoxy-4-methylpyridin-3-yl)boronic acid (0.082 g, 0.491 mmol) and PdCl2(dppf) (0.014 g, 0.019 mmol) in dioxane (8 mL) and aqueous saturated NaHCO3 (2 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 purified by preparative HPLC, eluting with a gradient of 40-45% ACN (containing 0.035% TFA) in H2O (containing 0.05% TFA) over a period of 6.5 minutes. The product-containing fractions were combined and solvent was removed on a rotary evaporator. The crude product was extracted into DCM, was washed sequentially with aqueous saturated NaHCO3, water, and brine, and was dried over Na2SO4. The volatiles were removed in vacuo to give the title compound as a white solid (0.053 g, 0.172 mmol, 46%). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.14 (s, 3H), 3.91 (s, 3H), 6.88 (s, 1H), 7.29 (s, 1H), 7.97 (s, 2H), 8.12 (s, 1H), 13.71 (s, 1H); ESI-MS m/z [M+H]+ calc'd for C15H12F3N3O, 308.1. found 308.15.

Workup

  1. concentrationThe reaction mixture was subsequently concentrated
  2. customthe crude residue was purified by preparative HPLC
  3. washeluting with a gradient of 40-45% ACN (containing 0.035% TFA) in H2O (containing 0.05% TFA) over a period of 6.5 minutes
  4. customsolvent was removed on a rotary evaporator
  5. extractionThe crude product was extracted into DCM
  6. washwas washed sequentially with aqueous saturated NaHCO3, water, and brine
  7. dry with materialwas dried over Na2SO4
  8. customThe volatiles were removed in vacuo

Sources & evidence

ORD record
ord-7406e11ebd0d416bbef77dafed783aba
Source dataset
uspto-grants-2016_09
Patent number
US09434743B2

Reaction notes

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