1,4-Dioxane → HCID 136387332, compound

HRID 718183Notes

Reaction equation

HRID 718183 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.P([O-])([O-])([O-])=O.[K+].[K+].[K+].O1[CH2:42][CH2:41]OCC1>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[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]([N:13]5[CH:14]=[C:41]([CH3:42])[N:16]=[CH:12]5)[CH:7]=4)=[C:14]([CH3:15])[N:13]=3)[N:17]=2)=[CH:23][CH:24]=1

Participants

6

Reactant 3

HCID 312751,4-Dioxane2×HCID 62657Potassium Phosphate, TribasicHCID 136641693HCID 136641693, compound

Product 1

HCID 136387332HCID 136387332, compoundYield 18%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent2×

Procedure

A solution of Pd2(dba)3 (0.012 g, 0.013 mmol) and Me4tBuXPhos (0.012 g, 0.025 mmol) in toluene (2 mL) and dioxane (4 mL) was heated in a screw capped tube (10 mL) at 120° C. for 3 min. The reaction mixture was cooled to RT and the pre-formed catalyst was transferred to a re-sealable pressure tube (50 mL) containing a degassed suspension of Example A8 (0.250 g, 0.628 mmol), 4-methyl imadazole (0.100 g, 1.218 mmol) and potassium phosphate (0.250 g, 1.178 mmol) in a mixture of toluene (4 mL) and dioxane (8 mL) followed by heating at 110° C. for 8 hours. The solids from the reaction mixture was filtered and washed with DCM and THF. The filtrate was completely evaporated and the residue was subjected to chromatography using (0-15% MeOH/DCM) to provide 3-(4-fluorophenyl)-1-(6-methyl-5-((2-(4-methyl-1H-imidazol-1-yl)pyridin-4-yl)oxy)pyridin-2-yl)-1H-1,2,4-triazol-5(4H)-one (0.050 g, 18% yield) as white solid. 1H NMR (400 MHz, DMSO-d6): δ 12.71 (s, 1H), 8.41 (d, J=1.4 Hz, 1H), 8.34 (d, J=5.8 Hz, 1H), 7.98-7.93 (m, 3H), 7.78 (d, J=8.8 Hz, 1H), 7.65 (t, J=1.3 Hz, 1H), 7.48 (br s, 1H), 7.40 (m, 2H), 6.82 (dd, J=5.8, 2.2 Hz, 1H), 2.38 (s, 3H), 2.13 (s, 3H); MS (ESI) m/z: 444.2 (M+H+).

Workup

  1. customcapped tube (10 mL) at 120° C. for 3 min
  2. customthe pre-formed catalyst was transferred to a re-sealable pressure tube
  3. temperatureby heating at 110° C. for 8 hours
  4. filtrationThe solids from the reaction mixture was filtered
  5. washwashed with DCM and THF
  6. customThe filtrate was completely evaporated

Sources & evidence

ORD record
ord-8d07eadfc24b44ae8af8cf24f4677dae
Source dataset
uspto-grants-2015_11
Patent number
US09193719B2

Reaction notes

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