Sodium Bicarbonate → 4-(6-methoxy-2-methylpyridin-3-yl)-6-(trifluoromethyl)-1H-indazole

HRID 58078Notes

Reaction equation

HRID 58078 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]=[C:21]([CH3:23])[C:20](B(O)O)=[CH:19][CH:18]=1.[C:27]([O-:30])(O)=[O:28].[Na+]>O1CCOCC1.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]>[C:27]([OH:30])([C:11]([F:14])([F:13])[F:12])=[O:28].[CH3:15][O:16][C:17]1[N:22]=[C:21]([CH3:23])[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)=[CH:19][CH:18]=1

Participants

7

Reactant 3

HCID 516892Sodium BicarbonateHCID 27630842-Methyl-6-methoxypyridine-3-boronic acidHCID 247292324-Bromo-6-(trifluoromethyl)-1H-indazole

Product 2

HCID 6422Trifluoroacetic acidHCID 897832044-(6-methoxy-2-methylpyridin-3-yl)-6-(trifluoromethyl)-1H-indazoleYield 47%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
140 °C

Procedure

A vial was charged with a mixture of 4-bromo-6-(trifluoromethyl)-1H-indazole (0.15 g, 0.566 mmol), (6-methoxy-2-methylpyridin-3-yl)boronic acid (0.123 g, 0.736 mmol) and PdCl2(dppf) (0.021 g, 0.028 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 microwave reactor. The reaction mixture was subsequently concentrated and the crude residue was purified by preparative HPLC, eluting with 45% ACN (containing 0.035% TFA) in H2O (containing 0.05% TFA) over a period of 6.5 minutes. The volatiles were removed in vacuo to give a TFA salt of the title compound as a light brown oil (82 mg, 47%). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.30 (s, 3H), 3.93 (s, 3H), 6.75-6.86 (m, 1H), 7.29 (d, J=1.26 Hz, 1H), 7.72 (d, J=8.34 Hz, 1H), 7.90-8.03 (m, 2H); 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 45% ACN (containing 0.035% TFA) in H2O (containing 0.05% TFA) over a period of 6.5 minutes
  4. customThe volatiles were removed in vacuo

Sources & evidence

ORD record
ord-5eae70f9cbb44cbcbe29c316c354d7fd
Source dataset
uspto-grants-2016_09
Patent number
US09434743B2

Reaction notes

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