Potassium Carbonate → 3-[1-(ethylsulfonyl)-4-piperidinyl]-5-[3-(1H-pyrazol-1-yl)phenyl]-1H-indole-7-carboxamide

HRID 562128Notes

Reaction equation

HRID 562128 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([C:11]([NH2:13])=[O:12])[CH:10]=1)[NH:7][CH:6]=[C:5]2[CH:14]1[CH2:19][CH2:18][N:17]([S:20]([CH2:23][CH3:24])(=[O:22])=[O:21])[CH2:16][CH2:15]1.[N:25]1([C:30]2[CH:31]=[C:32](B(O)O)[CH:33]=[CH:34][CH:35]=2)[CH:29]=[CH:28][CH:27]=[N:26]1.O1CCOCC1.C(=O)([O-])[O-].[K+].[K+]>O>[CH2:23]([S:20]([N:17]1[CH2:18][CH2:19][CH:14]([C:5]2[C:4]3[C:8](=[C:9]([C:11]([NH2:13])=[O:12])[CH:10]=[C:2]([C:34]4[CH:33]=[CH:32][CH:31]=[C:30]([N:25]5[CH:29]=[CH:28][CH:27]=[N:26]5)[CH:35]=4)[CH:3]=3)[NH:7][CH:6]=2)[CH2:15][CH2:16]1)(=[O:22])=[O:21])[CH3:24]

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 113844275-bromo-3-[1-(ethanesulfonyl)-4-piperidinyl]-1H-indole-7-carboxamideHCID 16640530(3-(1H-pyrazol-1-yl)phenyl)boronic acid

Product 1

HCID 577326993-[1-(ethylsulfonyl)-4-piperidinyl]-5-[3-(1H-pyrazol-1-yl)phenyl]-1H-indole-7-carboxamideYield 10%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To 5-bromo-3-[1-(ethylsulfonyl)-4-piperidinyl]-1H-indole-7-carboxamide (20 mg, 0.048 mmol) was added [3-(1H-pyrazol-1-yl)phenyl]boronic acid (36 mg, 0.193 mmol), dioxane (2.8 mL) and a solution of potassium carbonate (20 mg) in water (1.2 mL). To this mixture was added chloro-2-(dimethylaminomethyl)-ferrocen-1-yl-(dinorbornylphosphine)palladium(II) (3 mg, 0.005 mmol). The resulting mixture was reacted in a CEM microwave for 10 min at 160° C. then concentrated under a stream of nitrogen (greenhouse) at 80° C. The crude product was partitioned between water (2 mL) and CH2CL2 (2 mL). The layers were separated with a hydrophobic frit, and the aqueous layer was extracted with CH2CL2 (2×2 mL). The organic layers were pooled and concentrated under a stream of nitrogen at 80° C. Dimethyl sulfoxide (0.8 mL) was added to residue, which was sonicated for 10 sec. filtered through a cotton plug, and then filtered through a 0.2 μm filter. The crude product was purified on an Agilent MDAP using a Zorbax Eclipse XDB 610 21.2×50 mm column to afford 2.3 mg of the title compound (10%).

Workup

  1. customThe resulting mixture was reacted in a CEM microwave for 10 min at 160° C.
  2. concentrationthen concentrated under a stream of nitrogen (greenhouse) at 80° C
  3. customThe crude product was partitioned between water (2 mL) and CH2CL2 (2 mL)
  4. customThe layers were separated with a hydrophobic frit
  5. extractionthe aqueous layer was extracted with CH2CL2 (2×2 mL)
  6. concentrationconcentrated under a stream of nitrogen at 80° C
  7. additionDimethyl sulfoxide (0.8 mL) was added to residue, which
  8. customwas sonicated for 10 sec
  9. filtrationfiltered through a cotton plug
  10. filtrationfiltered through a 0.2 μm
  11. filtrationfilter
  12. customThe crude product was purified on an Agilent MDAP

Sources & evidence

ORD record
ord-b4f45f5d0d3849f6a8d3730f2058980b
Source dataset
uspto-grants-2011_11
Patent number
US08063071B2

Reaction notes

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