Cesium carbonate → HCID 136387334, compound

HRID 718194Notes

Reaction equation

HRID 718194 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]([CH:22]4[CH2:25][CH2:24][CH2:23]4)=[N:17]3)=[N:13][C:14]=2[CH3:15])[CH:5]=[CH:4][N:3]=1.[CH3:26][N:27]1[CH:31]=[C:30](B2OC(C)(C)C(C)(C)O2)[CH:29]=[N:28]1.C([O-])([O-])=O.[Cs+].[Cs+]>C(#N)C.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>[CH:22]1([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:30]5[CH:29]=[N:28][N:27]([CH3:26])[CH:31]=5)[CH:7]=4)=[C:14]([CH3:15])[N:13]=3)[N:17]=2)[CH2:25][CH2:24][CH2:23]1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 136641700HCID 136641700, compound

Product 1

HCID 136387334HCID 136387334, compoundYield 16.3%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
100 °C

Procedure

A suspension of 1-(5-((2-chloropyridin-4-yl)oxy)-6-methylpyridin-2-yl)-3-cyclobutyl-1H-1,2,4-triazol-5(4H)-one (0.300 g, 0.838 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.250 g, 1.202 mmol), Cs2CO3 (0.600 g, 1.842 mmol) and Pd(PPh3)4 (0.050 g, 0.043 mmol) in acetonitrile (20 mL) was heated at 100° C. under argon for 2 h. The solvent from the reaction mixture was completely evaporated and the residue partitioned between DCM (50 mL) and water (50 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, subjected to silica gel chromatography (0-100% THF/EtOAc) to provide 3-cyclobutyl-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 (0.055 g, 15%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 11.97 (s, 1H), 8.37 (d, J=5.7 Hz, 1H), 8.26 (s, 1H), 7.96 (s, 1H), 7.87 (d, J=8.8 Hz, 1H), 7.69 (d, J=8.8 Hz, 1H), 7.20 (d, J=2.4 Hz, 1H), 6.64 (dd, J=5.7, 2.4 Hz, 1H), 3.84 (s, 3H), 3.44 (m, 1H), 2.33 (s, 3H), 2.26 (m, 4H), 2.04 (m, 1H), 1.90 (m, 1H); MS (ESI) m/z: 404.2 (M+H+).

Workup

  1. customThe solvent from the reaction mixture was completely evaporated
  2. customthe residue partitioned between DCM (50 mL) and water (50 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

Sources & evidence

ORD record
ord-6e69aec43b8945d2953392a379b0a276
Source dataset
uspto-grants-2015_11
Patent number
US09193719B2

Reaction notes

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