Cesium carbonate → HCID 136387344, compound

HRID 718198Notes

Reaction equation

HRID 718198 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([C:26]([F:29])([F:28])[F:27])[CH2:25][CH2:24][CH2:23]4)=[N:17]3)=[N:13][C:14]=2[CH3:15])[CH:5]=[CH:4][N:3]=1.[CH3:30][N:31]1[CH:35]=[C:34](B2OC(C)(C)C(C)(C)O2)[CH:33]=[N:32]1.C([O-])([O-])=O.[Cs+].[Cs+]>CCO.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>[CH3:15][C:14]1[N:13]=[C:12]([N:16]2[C:20](=[O:21])[NH:19][C:18]([C:22]3([C:26]([F:29])([F:28])[F:27])[CH2:25][CH2:24][CH2:23]3)=[N:17]2)[CH:11]=[CH:10][C:9]=1[O:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([C:34]2[CH:33]=[N:32][N:31]([CH3:30])[CH:35]=2)[CH:7]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 136641685HCID 136641685, compound

Product 1

HCID 136387344HCID 136387344, compoundYield 4.9%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolvent

Conditions

Temperature
100 °C

Procedure

To a suspension of 1-(5((2-chloropyridin-4-yl)oxy)-6-methylpyridin-2-yl)-3-(1-(trifluoromethyl)cyclobutyl)-1H-1,2,4-triazol-5(4H)-one (0.240 g, 0.564 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.250 g, 1.202 mmol), Cs2CO3 (0.500 g, 1.535 mmol) and Pd(PPh3)4 (0.030 g, 0.026 mmol) in EtOH (20 mL) was heated at 100° C. 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 was separated and the aqueous layer saturated with solid sodium chloride and extracted with DCM (2×20 mL). The combined organics were dried, concentrated in vacuo, and purified by silica gel chromatography (0-40% THF/EtOAc) to provide 1-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-3-(1-(trifluoromethyl)cyclobutyl)-1H-1,2,4-triazol-5(4H)-one (0.013 g, 4.6%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 12.48 (s, 1H), 8.37 (d, J=5.7 Hz, 1H), 8.26 (s, 1H), 7.97 (s, 1H), 7.91 (d, J=8.8 Hz, 1H), 7.73 (d, J=8.8 Hz, 1H), 7.20 (d, J=2.4 Hz, 1H), 6.67 (dd, J=5.7, 2.4 Hz, 1H), 3.84 (s, 3H), 2.61 (m, 4H), 2.35 (s, 3H), 2.03 (t, J=8.2 Hz, 2H); MS (ESI) m/z: 472.2 (M+H+).

Workup

  1. customThe solvent from the reaction mixture was completely evaporated
  2. customthe residue was partitioned between DCM (30 mL) and water (30 mL)
  3. customThe organic layer was separated
  4. extractionthe aqueous layer saturated with solid sodium chloride and extracted with DCM (2×20 mL)
  5. customThe combined organics were dried
  6. concentrationconcentrated in vacuo
  7. custompurified by silica gel chromatography (0-40% THF/EtOAc)

Sources & evidence

ORD record
ord-3afe9ad7b5934aacb302c0db761136e6
Source dataset
uspto-grants-2015_11
Patent number
US09193719B2

Reaction notes

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