Potassium Phosphate, Tribasic → 3-chloro-2-fluoro-4-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)aniline

HRID 2279049Notes

Reaction equation

HRID 2279049 reaction equation
[Cl:1][C:2]1[C:3]([F:17])=[C:4]([CH:6]=[CH:7][C:8]=1[O:9][C:10]1[CH:15]=[CH:14][N:13]=[C:12](Cl)[CH:11]=1)[NH2:5].[CH3:18][N:19]1[CH:23]=[C:22](B2OC(C)(C)C(C)(C)O2)[CH:21]=[N:20]1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C.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>[Cl:1][C:2]1[C:3]([F:17])=[C:4]([CH:6]=[CH:7][C:8]=1[O:9][C:10]1[CH:15]=[CH:14][N:13]=[C:12]([C:22]2[CH:21]=[N:20][N:19]([CH3:18])[CH:23]=2)[CH:11]=1)[NH2:5]

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 904256883-Chloro-4-(2-chloropyridin-4-yloxy)-2-fluoroaniline

Product 1

HCID 904267863-chloro-2-fluoro-4-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)anilineYield 26%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 3-chloro-4-(2-chloropyridin-4-yloxy)-2-fluoroaniline (10 g, 36.8 mmol) in DMF (140 mL) and water (30 mL) was treated with 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (8.4 g, 40.5 mmol), K3PO4 (14.9 g, 73.6 mmol) and Pd(PPh3)4 (4.3 g, 3.7 mmol), sparged with N2 and heated at 80° C. for 12 h. The mixture was cooled to RT, poured into water and extracted with EtOAc (3×). The combined organics were washed with brine, dried over Na2SO4, concentrated to dryness and purified via silica gel chromatography to afford 3-chloro-2-fluoro-4-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)aniline (3.0 g, 26%). 1H NMR (400 MHz, DMSO-d6): δ 8.32 (d, J=6.0 Hz, 1 H), 8.24 (s, 1 H), 7.95 (s, 1 H), 7.15 (d, J=1.6 Hz, 1 H), 6.94 (d, J=8.8 Hz, 1 H), 6.80 (t, J=8.8 Hz, 1 H), 6.54-6.52 (m, 1 H), 5.51 (s, 2 H), 3.85 (s, 3H); MS (ESI): m/z 318.2 (M+H+).

Workup

  1. customsparged with N2
  2. temperatureThe mixture was cooled to RT
  3. additionpoured into water
  4. extractionextracted with EtOAc (3×)
  5. washThe combined organics were washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated to dryness
  8. custompurified via silica gel chromatography

Sources & evidence

ORD record
ord-2b9a29ead3e54dcaa1e907c393e4499b
Source dataset
uspto-grants-2015_09
Patent number
US09133183B2

Reaction notes

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