Potassium Carbonate → N-(5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyrazin-2-yl)acetamide

HRID 1049276Notes

Reaction equation

HRID 1049276 reaction equation
Cl[C:2]1[CH:7]=[C:6]([O:8][C:9]2[N:10]=[CH:11][C:12]([NH:15][C:16](=[O:18])[CH3:17])=[N:13][CH:14]=2)[CH:5]=[CH:4][N:3]=1.C([O-])([O-])=O.[K+].[K+].[CH3:25][N:26]1[CH:30]=[C:29](B2OC(C)(C)C(C)(C)O2)[CH:28]=[N:27]1>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:25][N:26]1[CH:30]=[C:29]([C:2]2[CH:7]=[C:6]([O:8][C:9]3[N:10]=[CH:11][C:12]([NH:15][C:16](=[O:18])[CH3:17])=[N:13][CH:14]=3)[CH:5]=[CH:4][N:3]=2)[CH:28]=[N:27]1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 90403635N-(5-((2-chloropyridin-4-yl)oxy)pyrazin-2-yl)acetamide

Product 1

HCID 90403923N-(5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyrazin-2-yl)acetamideYield 82%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a degassed solution of N-(5-((2-chloropyridin-4-yl)oxy)pyrazin-2-yl)acetamide (0.25 g, 0.945 mmol) in dioxane (6 mL) was added a solution of K2CO3 (0.261 g, 1.889 mmol) in water (1.5 mL), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.255 g, 1.228 mmol), and Pd(PPh3)4 (0.109 g, 0.094 mmol). The mixture was stirred at 80° C. for 3 h. The mixture was diluted with water (30 mL) and extracted with EtOAc (2×80 mL). The combined organics were washed with brine, dried (Na2SO4) and concentrated in vacuo. The crude product was purified by silica gel chromatography (MeOH/DCM) to afford N-(5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyrazin-2-yl)acetamide (240 mg, 82%) product as white solid. 1H NMR (400 MHz, DMSO-d6): δ 10.86 (s, 1H), 8.97 (d, J=1.4 Hz, 1H), 8.43 (dd, J=5.6, 0.5 Hz, 1H), 8.40 (d, J=1.4 Hz, 1H), 8.27 (s, 1H), 7.98 (d, J=0.7 Hz, 1H), 7.40 (m, 1H), 6.92 (dd, J=5.6, 2.4 Hz, 1H), 3.85 (s, 3H), 2.12 (s, 3H); MS (ESI) m/z: 311.1 (M+H+).

Workup

  1. extractionextracted with EtOAc (2×80 mL)
  2. washThe combined organics were washed with brine
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated in vacuo
  5. customThe crude product was purified by silica gel chromatography (MeOH/DCM)

Sources & evidence

ORD record
ord-162f38361a024f09adaee3adfc117ad1
Source dataset
uspto-grants-2016_07
Patent number
US09382228B2

Reaction notes

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