Sodium Bicarbonate → 4-(3,6-dimethoxypyridazin-4-yl)-6-(trifluoromethyl)-1H-indazole

HRID 58077Notes

Reaction equation

HRID 58077 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:18]=[N:19][C:20]([O:26][CH3:27])=[CH:21][C:22]=1B(O)O.[C:28]([O-:31])(O)=[O:29].[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:28]([OH:31])([C:11]([F:14])([F:13])[F:12])=[O:29].[CH3:15][O:16][C:17]1[N:18]=[N:19][C:20]([O:26][CH3:27])=[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

7

Reactant 3

HCID 516892Sodium BicarbonateHCID 247292324-Bromo-6-(trifluoromethyl)-1H-indazoleHCID 467392923,6-Dimethoxypyridazine-4-boronic acid

Product 2

HCID 6422Trifluoroacetic acidHCID 717368234-(3,6-dimethoxypyridazin-4-yl)-6-(trifluoromethyl)-1H-indazoleYield 4%

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), (3,6-dimethoxypyridazin-4-yl)boronic acid (0.135 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 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 volatiles were removed in vacuo to give a TFA salt of the title compound as a light brown solid (8 mg, 4%). 1H NMR (400 MHz, DMSO-d6) δ ppm 3.97 (s, 3H), 4.03 (s, 3H), 7.42 (s, 1H), 7.55 (d, J=1.01 Hz, 1H), 8.05 (s, 1H), 8.14 (s, 1H), 13.74 (s, 1H); ESI-MS m/z [M+H]+ calc'd for C14H11F3N4O2, 325.1. found 325.16.

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. customThe volatiles were removed in vacuo

Sources & evidence

ORD record
ord-ba0aa8d3d7494743920ba5e115f815b4
Source dataset
uspto-grants-2016_09
Patent number
US09434743B2

Reaction notes

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