Potassium Carbonate → HCID 67520829, compound

HRID 1926331Notes

Reaction equation

HRID 1926331 reaction equation
[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[CH:3]=[C:2]1[NH:10][C:11]1[CH:16]=[CH:15][C:14](Br)=[CH:13][N:12]=1.[CH3:18][N:19]1[CH:23]=[C:22](B2OC(C)(C)C(C)(C)O2)[CH:21]=[N:20]1.C(=O)([O-])[O-].[K+].[K+]>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.COCCOC>[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[CH:3]=[C:2]1[NH:10][C:11]1[CH:16]=[CH:15][C:14]([C:22]2[CH:21]=[N:20][N:19]([CH3:18])[CH:23]=2)=[CH:13][N:12]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 67521175HCID 67521175, compound

Product 1

HCID 67520829HCID 67520829, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

A suspension of 3-benzofuran-2-yl-5-bromopyridin-2-ylamine (65.2 mg, 0.226 mmol, 1 eq), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (56.7 mg, 0.272 mmol, 1.2 eq), Pd(PPh3)4 (18.6 mg, 0.0161 mmol, 7 mol %), and potassium carbonate (101.1 mg, 0.732 mmol, 3.2 eq) in a 4:1 mixture of DME:H2O (2.5 mL) was evacuated and charged with nitrogen several times, after which the sample was heated in the microwave reactor to 100° C. for 45 min. EtOAc was added to dilute the reaction, which was then washed with water (2×) and brine (1×), dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to dryness. The crude material was purified by column chromatography on silica gel [0.5″×10″ glass column, eluting with CH2Cl2:EtOAc 1:0→4:1→1:1→2:3→3:7→1:9→0:1]. Fractions containing product were combined and concentrated in vacuo. DCM and heptane were added to the residue and the solvent was concentrated in vacuo until all CH2Cl2 had been removed; a solid precipitated at this point. The solid was triturated in hot heptane and filtered off, giving the title compound as a yellow solid. 1H NMR (400 MHz, DMSO-d6): δ=3.86 (s, 3H), 6.28 (br s, 2H), 7.24-7.37 (m, 2H), 7.39 (d, J=0.8 Hz, 1H), 7.64-7.70 (m, 2H), 7.86 (d, J=0.8 Hz, 1H), 8.11 (d, J=2.3 Hz, 1H), 8.13 (s, 1H), 8.31 (d, J=2.3 Hz, 1H). MS (ES+): m/z=291.09 (100) [MH+]. HPLC: tR=2.65 min (ZQ3, polar—5 min).

Workup

  1. customH2O (2.5 mL) was evacuated
  2. additioncharged with nitrogen several times
  3. additionEtOAc was added
  4. additionto dilute
  5. customthe reaction, which
  6. washwas then washed with water (2×) and brine (1×)
  7. dry with materialdried over anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo to dryness
  10. customThe crude material was purified by column chromatography on silica gel [0.5″×10″ glass column
  11. washeluting with CH2Cl2:EtOAc 1:0→4:1→1:1→2:3→3:7→1:9→0:1]
  12. additionFractions containing product
  13. concentrationconcentrated in vacuo
  14. additionDCM and heptane were added to the residue
  15. concentrationthe solvent was concentrated in vacuo until all CH2Cl2
  16. customhad been removed
  17. customa solid precipitated at this point
  18. customThe solid was triturated in hot heptane
  19. filtrationfiltered off

Sources & evidence

ORD record
ord-ec54e6272b2a4ec1bc50794c1bcd0e1f
Source dataset
uspto-grants-2012_05
Patent number
US08178668B2

Reaction notes

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