Potassium Carbonate → N-(5-((2-(1H-pyrazol-4-yl)pyridin-4-yl)oxy)-6-methylpyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide

HRID 2278982Notes

Reaction equation

HRID 2278982 reaction equation
Cl[C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:10]=[CH:11][C:12]([NH:16][C:17]([N:19]3[CH2:23][CH2:22][N:21]([CH:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)[C:20]3=[O:30])=[O:18])=[N:13][C:14]=2[CH3:15])[CH:5]=[CH:4][N:3]=1.CC1(C)C(C)(C)OB([C:39]2[CH:40]=[N:41][NH:42][CH:43]=2)O1.C([O-])([O-])=O.[K+].[K+]>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>[NH:41]1[CH:40]=[C:39]([C:2]2[CH:7]=[C:6]([O:8][C:9]3[CH:10]=[CH:11][C:12]([NH:16][C:17]([N:19]4[CH2:23][CH2:22][N:21]([CH:24]5[CH2:29][CH2:28][O:27][CH2:26][CH2:25]5)[C:20]4=[O:30])=[O:18])=[N:13][C:14]=3[CH3:15])[CH:5]=[CH:4][N:3]=2)[CH:43]=[N:42]1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 27740104-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 90426065N-(5-((2-chloropyridin-4-yl)oxy)-6-methylpyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide

Product 1

HCID 86270216N-(5-((2-(1H-pyrazol-4-yl)pyridin-4-yl)oxy)-6-methylpyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamideYield 56%

Reagents, catalysts & solvents 3

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

Procedure

A solution of Example C3 (0.12 g, 0.28 mmol) in dioxane (4 mL) was sparged with Ar, treated with 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.08 g, 0.42 mmol), a solution of K2CO3 (0.077 g, 0.55 mmol) in water (1 mL) and Pd(PPh3)4 (0.032 g, 0.03 mmol) and heated at 90° C. overnight. The mixture was cooled to RT, diluted with water, extracted with EtOAc (2×) and the combined organics were washed with brine, dried over Na2SO4, concentrated to dryness and purified via silica gel chromatography (MeOH/DCM) to afford N-(5-((2-(1H-pyrazol-4-yl)pyridin-4-yl)oxy)-6-methylpyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide (72 mg, 56%). 1H NMR (400 MHz, DMSO-d6): δ 13.05 (br s, 1 H), 10.89 (s, 1 H), 8.35 (d, J=5.7 Hz, 1 H), 8.31 (brs, 1 H), 8.03 (s, 1 H), 7.89 (d, J=8.8 Hz, 1 H), 7.61 (d, J=8.8 Hz, 1 H), 7.28 (d, J=2.4 Hz, 1 H), 6.56 (dd, J=5.7, 2.4 Hz, 1 H), 3.95-3.77 (m, 5 H), 3.43-3.39 (m, 4 H), 2.24 (s, 3 H), 1.71-1.70 (m, 2 H), 1.60 (d, J=12.4 Hz, 2 H); MS (ESI) m/z: 464.2 (M+H+).

Workup

  1. extractionextracted with EtOAc (2×)
  2. washthe combined organics were washed with brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated to dryness
  5. custompurified via silica gel chromatography (MeOH/DCM)

Sources & evidence

ORD record
ord-fb3e24053291481aa71f7ee2bcca943a
Source dataset
uspto-grants-2015_09
Patent number
US09133183B2

Reaction notes

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