Potassium Carbonate → HCID 136641702, compound

HRID 718196Notes

Reaction equation

HRID 718196 reaction equation
[CH2:1]([O:8][CH2:9][C:10]([C:13]1[NH:17][C:16](=[O:18])[N:15]([C:19]2[CH:24]=[CH:23][C:22]([O:25][C:26]3[CH:31]=[CH:30][N:29]=[C:28](Cl)[CH:27]=3)=[C:21]([CH3:33])[N:20]=2)[N:14]=1)([CH3:12])[CH3:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:34][N:35]1[CH:39]=[C:38](B2OC(C)(C)C(C)(C)O2)[CH:37]=[N:36]1.C([O-])([O-])=O.[K+].[K+].[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.CCOC(C)=O.O.O1CCOCC1>[CH2:1]([O:8][CH2:9][C:10]([C:13]1[NH:17][C:16](=[O:18])[N:15]([C:19]2[CH:24]=[CH:23][C:22]([O:25][C:26]3[CH:31]=[CH:30][N:29]=[C:28]([C:38]4[CH:37]=[N:36][N:35]([CH3:34])[CH:39]=4)[CH:27]=3)=[C:21]([CH3:33])[N:20]=2)[N:14]=1)([CH3:12])[CH3:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

9

Reactant 4

HCID 11430Potassium CarbonateHCID 25517Ammonium ChlorideHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 136641687HCID 136641687, compound

Product 1

HCID 136641702HCID 136641702, compoundYield 91.1%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

3-(1-(Benzyloxy)-2-methylpropan-2-yl)-1-(5-((2-chloropyridin-4-yl)oxy)-6-methylpyridin-2-yl)-1H-1,2,4-triazol-5(4H)-one (0.41 g, 0.88 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.24 g, 1.14 mmol), and K2CO3 (0.32 g, 2.29 mmol) were suspended in a solution of dioxane (5.0 mL) and water (1.0 mL). The suspension was sonicated and sparged with Ar for 10 min followed by the addition of Pd(PPh3)4 (0.10 g, 0.09 mmol). The reaction mixture was stirred at 85° C. for 12 h, allowed to cool to RT, and suspended between sat. NH4Cl (aq.) (15 mL) and EtOAc (20 mL). The organic phase was collected and the aqueous phase was extracted with EtOAc (3×15 mL). The combined organics were dried (Na2SO4) and concentrated in vacuo to afford an orange oil. The residue was purified by silica gel chromatography (MeOH/DCM) to afford 3-(1-(benzyloxy)-2-methylpropan-2-yl)-1-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-1H-1,2,4-triazol-5(4H)-one (0.41 g, 91%) as a viscous, pale yellow oil. 1H NMR (400 MHz, DMSO-d6): δ 11.95 (s, 1H), 8.36 (d, J=5.6 Hz, 1H), 8.26 (s, 1H), 7.96 (s, 1H), 7.86 (d, J=8.8 Hz, 1H), 7.69 (d, J=8.8 Hz, 1H), 7.31-7.29 (m, 5H), 7.18 (d, J=2.4 Hz, 1H), 6.66 (dd, J=5.7, 2.4 Hz, 1H), 4.49 (s, 2H), 3.83 (s, 3H), 3.50 (s, 2H), 2.33 (s, 3H), 1.27 (s, 6H); MS (ESI) m/z: 512.3 (M+H+).

Workup

  1. customThe suspension was sonicated
  2. customsparged with Ar for 10 min
  3. temperatureto cool to RT
  4. customThe organic phase was collected
  5. extractionthe aqueous phase was extracted with EtOAc (3×15 mL)
  6. dry with materialThe combined organics were dried (Na2SO4)
  7. concentrationconcentrated in vacuo
  8. customto afford an orange oil
  9. customThe residue was purified by silica gel chromatography (MeOH/DCM)

Sources & evidence

ORD record
ord-c6b6c17a3ebc42f296bec64224004e62
Source dataset
uspto-grants-2015_11
Patent number
US09193719B2

Reaction notes

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