Ethyl Acetate → HCID 136387297, compound

HRID 718180Notes

Reaction equation

HRID 718180 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]([CH2:25][CH3:26])([CH3:24])[CH3:23])=[N:17]3)=[N:13][C:14]=2[CH3:15])[CH:5]=[CH:4][N:3]=1.[CH3:27][N:28]1[CH:32]=[C:31](B2OC(C)(C)C(C)(C)O2)[CH:30]=[N:29]1.C([O-])([O-])=O.[K+].[K+].CCOC(C)=O>O1CCOCC1.O.CC#N.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>[CH3:15][C:14]1[N:13]=[C:12]([N:16]2[C:20](=[O:21])[NH:19][C:18]([C:22]([CH2:25][CH3:26])([CH3:24])[CH3:23])=[N:17]2)[CH:11]=[CH:10][C:9]=1[O:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([C:31]2[CH:30]=[N:29][N:28]([CH3:27])[CH:32]=2)[CH:7]=1

Participants

9

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 136930523HCID 136930523, compound

Product 1

HCID 136387297HCID 136387297, compoundYield 85.2%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolventHCID 18373917Acetonitrile--water (1/1)Solvent

Conditions

Temperature
85 °C

Procedure

1-(5-((2-Chloropyridin-4-yl)oxy)-6-methylpyridin-2-yl)-3-(tert-pentyl)-1H-1,2,4-triazol-5(4H)-one (0.15 g, 0.40 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.11 g, 0.52 mmol), and K2CO3 (0.14 g, 1.04 mmol) were suspended in dioxane (1.7 mL) and water (0.33 mL). The suspension was sonicated and sparged with Ar for 10 min. Pd(PPh3)4 (0.046 g, 0.040 mmol) was added and the reaction mixture was stirred at 85° C. for 12 h. EtOAc (15 mL) was added and the suspension was filtered through a pad of diatomaceous earth. The filter cake was washed with EtOAc (3×5 mL) and the combined filtrates were concentrated in vacuo. The residue was purified by silica gel chromatography (MeOH/DCM). Product was isolated as a colorless oil that was dissolved in MeCN/water, frozen to −78° C., and lyophilized to afford 1-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-3-(tert-pentyl)-1H-1,2,4-triazol-5(4H)-one (0.143 g, 79%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 11.91 (s, 1H), 8.37 (d, J=5.7 Hz, 1H), 8.25 (s, 1H), 7.96 (s, 1H), 7.86 (d, J=8.7 Hz, 1H), 7.68 (d, J=8.7 Hz, 1H), 7.18 (s, 1H), 6.66 (d, J=5.6 Hz, 1H), 3.84 (s, 3H), 2.33 (s, 3H), 1.61 (q, J=7.6 Hz, 2H), 1.23 (s, 6H), 0.76 (t, J=7.3 Hz, 3H); MS (ESI) m/z: (M+H+).

Workup

  1. customThe suspension was sonicated
  2. customsparged with Ar for 10 min
  3. filtrationthe suspension was filtered through a pad of diatomaceous earth
  4. washThe filter cake was washed with EtOAc (3×5 mL)
  5. concentrationthe combined filtrates were concentrated in vacuo
  6. customThe residue was purified by silica gel chromatography (MeOH/DCM)
  7. customProduct was isolated as a colorless oil that
  8. temperaturefrozen to −78° C.

Sources & evidence

ORD record
ord-1dd64b458f264b8791905fba8182e3d7
Source dataset
uspto-grants-2015_11
Patent number
US09193719B2

Reaction notes

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