Potassium Carbonate → HCID 136387348, compound

HRID 718202Notes

Reaction equation

HRID 718202 reaction equation
[C:1]([C:5]1[NH:9][C:8](=[O:10])[N:7]([C:11]2[CH:16]=[CH:15][C:14]([O:17][C:18]3[CH:23]=[C:22](Cl)[N:21]=[CH:20][N:19]=3)=[C:13]([CH3:25])[N:12]=2)[N:6]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:26][N:27]1[CH:31]=[C:30](B2OC(C)(C)C(C)(C)O2)[CH:29]=[N:28]1.C([O-])([O-])=O.[K+].[K+].O1CCOCC1>[NH4+].[Cl-].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.O>[C:1]([C:5]1[NH:9][C:8](=[O:10])[N:7]([C:11]2[CH:16]=[CH:15][C:14]([O:17][C:18]3[CH:23]=[C:22]([C:30]4[CH:29]=[N:28][N:27]([CH3:26])[CH:31]=4)[N:21]=[CH:20][N:19]=3)=[C:13]([CH3:25])[N:12]=2)[N:6]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 136930510HCID 136930510, compound

Product 1

HCID 136387348HCID 136387348, compoundYield 48.3%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
85 °C

Procedure

3-(tert-Butyl)-1-(5-((6-chloropyrimidin-4-yl)oxy)-6-methylpyridin-2-yl)-1H-1,2,4-triazol-5(4H)-one (0.10 g, 0.28 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.08 g, 0.36 mmol), and K2CO3 (0.10 g, 0.72 mmol) were suspended in a solution of dioxane (2.5 mL) and water (0.50 mL). The suspension was sonicated and sparged with Ar for 10 min. Pd(PPh3)4 (0.032 g, 0.028 mmol) was added and the reaction mixture was stirred at 85° C. for 16 h. The mixture was diluted with sat. NH4Cl (aq) 5 mL) and the resultant emulsion was extracted with EtOAc (4×10 mL). The combined organics were dried (Na2SO4) and concentrated in vacuo. The residue was purified by silica gel chromatography (MeOH/DCM) to afford a brown amorphous solid that was triturated with MeCN (1.5 mL). A white precipitate formed following sonication and was isolated by filtration and dried to afford 3-(tert-butyl)-1-(6-methyl-5-((6-(1-methyl-1H-pyrazol-4-yl)pyrimidin-4-yl)oxy)pyridin-2-yl)-1H-1,2,4-triazol-5(4H)-one (0.055 g, 48.3%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 11.95 (s, 1H), 8.61 (d, J=1.1 Hz, 1H), 8.48 (s, 1H), 8.17 (s, 1H), 7.80 (d, J=8.7 Hz, 1H), 7.73 (d, J=8.7 Hz, 1H), 7.46 (d, J=1.1 Hz, 1H), 3.89 (s, 3H), 2.29 (s, 3H), 1.27 (s, 9H); MS (ESI) m/z: 420.3 (M+H+).

Workup

  1. customThe suspension was sonicated
  2. customsparged with Ar for 10 min
  3. extractionwas extracted with EtOAc (4×10 mL)
  4. dry with materialThe combined organics were dried (Na2SO4)
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by silica gel chromatography (MeOH/DCM)
  7. customto afford a brown amorphous solid
  8. customthat was triturated with MeCN (1.5 mL)
  9. customA white precipitate formed
  10. customsonication
  11. customwas isolated by filtration
  12. customdried

Sources & evidence

ORD record
ord-d0ec0d66d30d4a819c6b683bf2e069c0
Source dataset
uspto-grants-2015_11
Patent number
US09193719B2

Reaction notes

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