Potassium Carbonate → HCID 136387300, compound

HRID 718182Notes

Reaction equation

HRID 718182 reaction equation
Cl[C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:10]=[CH:11][C:12]([N:16]3[C:20](=[O:21])[NH:19][C:18]([C:22]4[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=4)=[N:17]3)=[N:13][C:14]=2[CH3:15])[CH:5]=[CH:4][N:3]=1.[CH3:29][N:30]1[CH:34]=[C:33](B2OC(C)(C)C(C)(C)O2)[CH:32]=[N:31]1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.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>[F:28][C:25]1[CH:26]=[CH:27][C:22]([C:18]2[NH:19][C:20](=[O:21])[N:16]([C:12]3[CH:11]=[CH:10][C:9]([O:8][C:6]4[CH:5]=[CH:4][N:3]=[C:2]([C:33]5[CH:32]=[N:31][N:30]([CH3:29])[CH:34]=5)[CH:7]=4)=[C:14]([CH3:15])[N:13]=3)[N:17]=2)=[CH:23][CH:24]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 136641693HCID 136641693, compound

Product 1

HCID 136387300HCID 136387300, compoundYield 45.5%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
100 °C

Procedure

A suspension of Example A8 (0.300 g, 0.754 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.250 g, 1.202 mmol), K2CO3 (0.200 g, 1.447 mmol) in a mixture of dioxane/water (10:1) (11 mL) was degassed for 5 minutes with argon purge. The reaction mixture was treated with Pd(PPh3)4 (0.020 g, 0.017 mmol) and heated at 100° C. under argon over night. The solvent from the reaction mixture was completely evaporated and the residue was partitioned between DCM (30 mL) and water (30 mL). The organic layer separated and the aqueous layer extracted with dichloromethane (2×15 mL). The combined organics were dried and concentrated to a small volume and purified by silica gel chromatography (0-100% THF/DCM) to provide 3-(4-fluorophenyl)-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 (0.152 g, 45%) as white solid. 1H NMR (400 MHz, DMSO-d6): δ 12.71 (s, 1H), 8.38 (d, J=5.7 Hz, 1H), 8.27 (s, 1H), 7.98-7.94 (m, 4H), 7.74 (d, J=8.8 Hz, 1H), 7.40 (t, J=8.8 Hz, 2H), 7.23 (d, J=2.4 Hz, 1H), 6.67 (dd, J=5.7, 2.4 Hz, 1H), 3.84 (s, 3H), 2.37 (s, 3H); MS (ESI) m/z: 444.2 (M+H+).

Workup

  1. customwas degassed for 5 minutes with argon
  2. custompurge
  3. customThe solvent from the reaction mixture was completely evaporated
  4. customthe residue was partitioned between DCM (30 mL) and water (30 mL)
  5. customThe organic layer separated
  6. extractionthe aqueous layer extracted with dichloromethane (2×15 mL)
  7. customThe combined organics were dried
  8. concentrationconcentrated to a small volume
  9. custompurified by silica gel chromatography (0-100% THF/DCM)

Sources & evidence

ORD record
ord-59d4418917c4483e959cc11e10097f4a
Source dataset
uspto-grants-2015_11
Patent number
US09193719B2

Reaction notes

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