Potassium Carbonate → 6-Fluoro-1-[1-[6-(1-methylpyrazol-4-yl)pyridazin-3-yl]piperidin-4-yl]-2,3-dihydroindole

HRID 512822Notes

Reaction equation

HRID 512822 reaction equation
Cl[C:2]1[N:7]=[N:6][C:5]([N:8]2[CH2:13][CH2:12][CH:11]([N:14]3[C:22]4[C:17](=[CH:18][CH:19]=[C:20]([F:23])[CH:21]=4)[CH2:16][CH2:15]3)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[CH3:24][N:25]1[CH:29]=[C:28](B2OC(C)(C)C(C)(C)O2)[CH:27]=[N:26]1.C([O-])([O-])=O.[K+].[K+]>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>[F:23][C:20]1[CH:21]=[C:22]2[C:17]([CH2:16][CH2:15][N:14]2[CH:11]2[CH2:12][CH2:13][N:8]([C:5]3[N:6]=[N:7][C:2]([C:28]4[CH:27]=[N:26][N:25]([CH3:24])[CH:29]=4)=[CH:3][CH:4]=3)[CH2:9][CH2:10]2)=[CH:18][CH:19]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 896144661-(1-(6-Chloropyridazin-3-yl)piperidin-4-yl)-6-fluoroindoline

Product 1

HCID 715715696-Fluoro-1-[1-[6-(1-methylpyrazol-4-yl)pyridazin-3-yl]piperidin-4-yl]-2,3-dihydroindole

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
100 °C

Procedure

In a two-neck flask was placed 1-(1-(6-chloropyridazin-3-yl)piperidin-4-yl)-6-fluoroindoline, prepared as in STEP 3 above (2.33 g, 7 mmol, 1 equiv), 1-methylpyrazole-4-boronic acid pinacol ester (1.75 g, 8.4 mmol, 1.2 equiv), K2CO3 (3.86 g, 28 mmol, 4.0 equiv), and Pd(PPh3)4 (809 mg, 0.7 mmol, 0.1 equiv). The resulting mixture was degassed and refilled with N2 (3 times). 1,4-Dioxane/H2O (30 mL/6 mL) was added and the resulting mixture was heated at 100° C. for 3 h. The resulting mixture was poured into EtOAc/H2O (100 mL/100 mL). The organic layer was washed with brine (100 mL), dried (Na2SO4), and filtered. The solvent was removed by roto-evaporator, and the resulting residue was purified by column using EtOAc as the eluent to yield the title compound as a solid.

Workup

  1. customIn a two-neck flask was placed
  2. customThe resulting mixture was degassed
  3. additionrefilled with N2 (3 times)
  4. addition1,4-Dioxane/H2O (30 mL/6 mL) was added
  5. additionThe resulting mixture was poured into EtOAc/H2O (100 mL/100 mL)
  6. washThe organic layer was washed with brine (100 mL)
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. customThe solvent was removed by roto-evaporator
  10. customthe resulting residue was purified by column

Sources & evidence

ORD record
ord-a85c23ff2eb54f1a9b9d4b86646b8c57
Source dataset
uspto-grants-2015_08
Patent number
US09102669B2

Reaction notes

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