Cesium carbonate → HCID 136387317, compound

HRID 718190Notes

Reaction equation

HRID 718190 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[CH2:24][CH2:23]4)=[N:17]3)=[N:13][C:14]=2[CH3:15])[CH:5]=[CH:4][N:3]=1.[CH3:25][N:26]1[CH:30]=[C:29](B2OC(C)(C)C(C)(C)O2)[CH:28]=[N:27]1.C([O-])([O-])=O.[Cs+].[Cs+]>CC#N.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:29]5[CH:28]=[N:27][N:26]([CH3:25])[CH:30]=5)[CH:7]=4)=[C:14]([CH3:15])[N:13]=3)[N:17]=2)[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 136641699HCID 136641699, compound

Product 1

HCID 136387317HCID 136387317, compoundYield 70.6%

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-cyclopropyl-1H-1,2,4-triazol-5(4H)-one (0.285 g, 0.829 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 MeCN (20 mL) was heated at 100° C. under argon for 4 hours. The solvent from the reaction mixture was completely evaporated and the residue was 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, and purified by silica gel chromatography (0-20% MeOH/DCM) to provide 3-cyclopropyl-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 (0.228 g, 66%) as a white solid. 1H NMR (400 MHz, dmso): δ 11.80 (s, 1H), 8.36 (d, J=5.7 Hz, 1H), 8.26 (s, 1H), 7.96 (s, 1H), 7.86 (d, J=8.8 Hz, 1H), 7.68 (d, J=8.8 Hz, 1H), 7.20 (d, J=2.4 Hz, 1H), 6.63 (dd, J=5.7, 2.4 Hz, 1H), 3.84 (s, 3H), 2.32 (s, 3H), 1.87 (tt, J=8.4, 5.1 Hz, 1H), 0.95 (m, 4H); MS (ESI) m/z: 390.2 (M+H+).

Workup

  1. customThe solvent from the reaction mixture was completely evaporated
  2. customthe residue was 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
  7. custompurified by silica gel chromatography (0-20% MeOH/DCM)

Sources & evidence

ORD record
ord-5d5cc49474c44d90bcef96a72af1c231
Source dataset
uspto-grants-2015_11
Patent number
US09193719B2

Reaction notes

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