1,4-Dioxane → HCID 86729379, compound

HRID 521218Notes

Reaction equation

HRID 521218 reaction equation
[C:1]([C:4]1[C:5]([NH:26][C:27]2[CH:28]=[N:29][C:30](Cl)=[CH:31][CH:32]=2)=[N:6][N:7]([C:9]2([CH2:23][C:24]#[N:25])[CH2:14][CH2:13][N:12]([C:15]([O:17][CH2:18][C:19]([F:22])([F:21])[F:20])=[O:16])[CH2:11][CH2:10]2)[CH:8]=1)(=[O:3])[NH2:2].[CH3:34][N:35]1[CH:39]=[C:38](B2OC(C)(C)C(C)(C)O2)[CH:37]=[N:36]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].O1CCOCC1>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O>[C:1]([C:4]1[C:5]([NH:26][C:27]2[CH:28]=[N:29][C:30]([C:38]3[CH:37]=[N:36][N:35]([CH3:34])[CH:39]=3)=[CH:31][CH:32]=2)=[N:6][N:7]([C:9]2([CH2:23][C:24]#[N:25])[CH2:14][CH2:13][N:12]([C:15]([O:17][CH2:18][C:19]([F:22])([F:21])[F:20])=[O:16])[CH2:11][CH2:10]2)[CH:8]=1)(=[O:3])[NH2:2]

Participants

7

Reactant 4

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 86729378HCID 86729378, compound

Product 1

HCID 86729379HCID 86729379, compound

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

2,2,2-Trifluoroethyl 4-(4-carbamoyl-3-(6-chloropyridin-3-ylamino)-1H-pyrazol-1-yl)-4-(cyanomethyl)piperidine-1-carboxylate (45 mg, 0.093 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (23 mg, 0.11 mmol), Pd(dppf)Cl2 (8 mg, 0.009 mmol), potassium phosphate (59 mg, 0.28 mmol), 1,4-dioxane (0.25 mL), and water (0.03 mL) were combined in a 4 mL vial. The vial was then sealed and flushed with argon. The mixture was heated to 90° C. and was allowed to stir for 90 minutes. The mixture was cooled to ambient temperature, diluted with EtOAc and washed sequentially with water and brine. The organic layer was dried with anhydrous MgSO4, and concentrated in vacuo. The residue was purified by MPLC on silica gel (using a gradient elution of 0-10% MeOH/DCM) to afford the title compound, Example #11-1.

Workup

  1. customThe vial was then sealed
  2. customflushed with argon
  3. temperatureThe mixture was cooled to ambient temperature
  4. additiondiluted with EtOAc
  5. washwashed sequentially with water and brine
  6. dry with materialThe organic layer was dried with anhydrous MgSO4
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by MPLC on silica gel (
  9. washa gradient elution of 0-10% MeOH/DCM)

Sources & evidence

ORD record
ord-d827f1d876ba49deab24c083c1452846
Source dataset
uspto-grants-2016_05
Patent number
US09328099B2

Reaction notes

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