Potassium Carbonate → HCID 67468806, compound

HRID 1046014Notes

Reaction equation

HRID 1046014 reaction equation
[F:1][C:2]1[CH:30]=[C:29]([NH2:31])[C:28]([F:32])=[CH:27][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[C:7]([N:11]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[C:6]=1I.[CH3:33][N:34]1[CH:38]=[C:37](B2OC(C)(C)C(C)(C)O2)[CH:36]=[N:35]1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O.CCOC(C)=O>[NH2:31][C:29]1[C:28]([F:32])=[CH:27][C:3]([O:4][C:5]2[CH:10]=[CH:9][N:8]=[C:7]([N:11]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[C:6]=2[C:37]2[CH:36]=[N:35][N:34]([CH3:33])[CH:38]=2)=[C:2]([F:1])[CH:30]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 680094164-(2,5-Difluoro-4-aminophenoxy)-3-iodo-2-[bis[(1,1-dimethylethoxy)carbonyl]amino]pyridine

Product 1

HCID 67468806HCID 67468806, compoundYield 81%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a degassed solution of 4-(2,5-difluoro-4-aminophenoxy)-3-iodo-2-[bis[(1,1-dimethylethoxy)carbonyl]amino]pyridine (0.7 g, 1.24 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.52 g, 2.48 mmol) in dioxane (15 mL) was added K2CO3 (0.51 g, 3.7 mmol) in water (3 mL). Tetrakis (triphenylphosphine)Palladium(0) (0.14 g, 0.12 mmol) was added and the reaction mixture was stirred at 100° C. for 3 h. The mixture was diluted with water (40 mL) and EtOAc (50 mL). The layers were separated, and the aq. layer was extracted with EtOAc (20 mL). The combined organics were washed with brine, dried (Na2SO4) and concentrated in vacuo. The residue was purified by silica gel chromatography (EtOAc-hexanes) to afford 4-(4-amino-2,5-difluorophenoxy)-3-(1-methyl-1H-pyrazol-4-yl)-2-[bis[(1,1-dimethylethoxy)carbonyl]amino]pyridine as a colorless foam (0.52 g, 81% yield). 1H NMR (400 MHz, DMSO-d6): δ 8.17 (d, J=5.6 Hz, 1H), 7.84 (s, 1H), 7.48 (d, J=0.8 Hz, 1H), 7.21 (dd, J=11.2 Hz, 7.6 Hz, 1H), 6.70 (m, 2H), 5.50 (s, 2H), 3.86 (s, 3H), 1.25 (s, 18H); MS (ESI) m/z: 518.3 (M+H+).

Workup

  1. customThe layers were separated
  2. extractionthe aq. layer was extracted with EtOAc (20 mL)
  3. washThe combined organics were washed with brine
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by silica gel chromatography (EtOAc-hexanes)

Sources & evidence

ORD record
ord-6c8c4e0361704733be1bc21b2a070c9d
Source dataset
uspto-grants-2013_10
Patent number
US08569319B2

Reaction notes

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