Potassium Carbonate → HCID 67468307, compound

HRID 1046008Notes

Reaction equation

HRID 1046008 reaction equation
[NH2:1][C:2]1[C:16]([F:17])=[CH:15][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH2:13])[C:8]=2I)=[C:4]([F:18])[CH:3]=1.[CH3:19][N:20]1[CH:24]=[C:23](B2OC(C)(C)C(C)(C)O2)[CH:22]=[N:21]1.C([O-])([O-])=O.[K+].[K+].C([O-])(O)=O.[Na+]>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>[NH2:1][C:2]1[C:16]([F:17])=[CH:15][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH2:13])[C:8]=2[C:23]2[CH:22]=[N:21][N:20]([CH3:19])[CH:24]=2)=[C:4]([F:18])[CH:3]=1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 516892Sodium BicarbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 67466807HCID 67466807, compound

Product 1

HCID 67468307HCID 67468307, compoundYield 65.2%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

To a degassed solution of 4-(4-amino-2,5-difluorophenoxy)-3-iodopyridin-2-amine (0.33 g, 0.91 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.28 g, 1.36 mmol) in dioxane (5 ml) was added a degassed solution of K2CO3 (0.37 g, 2.73 mmol) in water (2 mL) and tetrakis(triphenylphosphine)palladium(0) (0.105 g, 0.09 mmol). The resultant mixture was stirred for 16 h at 90° C. Sat. NaHCO3 solution (35 mL) was added. The resultant mixture was extracted with EtOAc (2×30 mL). The combined organics were washed with brine, dried (Na2SO4) and concentrated in vacuo. The residue was purified by silica gel chromatography (MeOH/CH2Cl2) to afford 4-(4-amino-2,5-difluorophenoxy)-3-(1-methyl-1H-pyrazol-4-yl)pyridin-2-amine (188 mg, 65.2%) as white solid (188 mg, 65.2% yield). 1H NMR (400 MHz, DMSO-d6): δ 7.85 (s, 1H), 7.70 (d, J=6.0 Hz, 1H), 7.57 (s, 1H), 7.06 (dd, J=11.2 Hz, 7.2 Hz, 1H), 6.66 (dd, J=12.0 Hz, 8.0 Hz, 1H), 5.86 (d, J=5.6 Hz, 1H), 5.60 (s, 2H), 5.39 (s, 2H), 3.85 (s, 3H); MS (ESI) m/z: 318.1 (M+H+).

Workup

  1. extractionThe resultant mixture was extracted with EtOAc (2×30 mL)
  2. washThe combined organics were washed with brine
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by silica gel chromatography (MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-058324c9ac3d42c897e59d90e7e5535c
Source dataset
uspto-grants-2013_10
Patent number
US08569319B2

Reaction notes

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