Sodium Carbonate → 3-(1-methyl-1H-pyrazol-4-yl)-6-(6-methyl-[1,2,4]triazolo[4,3-b]pyridazin-3-ylsulfanyl)-quinoline

HRID 1890959Notes

Reaction equation

HRID 1890959 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]2[C:10]([CH:11]=1)=[CH:9][C:8]([S:12][C:13]1[N:17]3[N:18]=[C:19]([CH3:22])[CH:20]=[CH:21][C:16]3=[N:15][N:14]=1)=[CH:7][CH:6]=2.[CH3:23][N:24]1[CH:28]=[C:27](B2OC(C)(C)C(C)(C)O2)[CH:26]=[N:25]1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC>[CH3:23][N:24]1[CH:28]=[C:27]([C:2]2[CH:3]=[N:4][C:5]3[C:10]([CH:11]=2)=[CH:9][C:8]([S:12][C:13]2[N:17]4[N:18]=[C:19]([CH3:22])[CH:20]=[CH:21][C:16]4=[N:15][N:14]=2)=[CH:7][CH:6]=3)[CH:26]=[N:25]1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 249009763-Bromo-6-(6-methyl-[1,2,4]triazolo[4,3-b]pyridazin-3-ylsulfanyl)-quinoline

Product 1

HCID 249009753-(1-methyl-1H-pyrazol-4-yl)-6-(6-methyl-[1,2,4]triazolo[4,3-b]pyridazin-3-ylsulfanyl)-quinolineYield 28%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Procedure

A microwave vessel was charged with 3-bromo-6-(6-methyl-[1,2,4]triazolo[4,3-b]pyridazin-3-ylsulfanyl)-quinoline (40 mg, 0.107 mmol), 1-methyl-4-pyrazoleboronic acid pinacol ester (27 mg, 0.129 mmol), and dichlorobis(triphenylphosphine) palladium(0) (4 mg, 0.005 mmol). 1,2-Dimethoxyethane (0.5 mL) and a 2 M aqueous solution of sodium carbonate (0.5 mL) were added. The vessel was capped and microwaved at 120° C. for 30 min. The organic layer was separated, the aqueous layer was extracted with 10% methanol/dichloromethane (2×), and the combined organics were adsorbed on silica gel. Purification by flash chromatography on silica gel using a gradient of 0-6% methanol/dichloromethane afforded 28 mg of an off white solid. The solid was further purified by mass-triggered HPLC (5-95% CH3CN/H2O, 0.1% HCOOH modifier) to provide 11 mg of 3-(1-methyl-1H-pyrazol-4-yl)-6-(6-methyl-[1,2,4]triazolo[4,3-b]pyridazin-3-ylsulfanyl)-quinoline as a white solid (28% yield).

Workup

  1. customThe vessel was capped
  2. custommicrowaved at 120° C. for 30 min
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted with 10% methanol/dichloromethane (2×)
  5. customPurification by flash chromatography on silica gel using a gradient of 0-6% methanol/dichloromethane
  6. customafforded 28 mg of an off white solid
  7. customThe solid was further purified by mass-triggered HPLC (5-95% CH3CN/H2O, 0.1% HCOOH modifier)

Sources & evidence

ORD record
ord-2b4ed8ba34f34f5080b903ec8df655b7
Source dataset
uspto-grants-2013_08
Patent number
US08507489B2

Reaction notes

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