Ethyl Acetate → HCID 57732687, compound

HRID 562130Notes

Reaction equation

HRID 562130 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.C(=O)([O-])[O-].[K+].[K+].S(O)(O)(=O)=O.[NH2:36][C:37]1[CH:38]=[C:39](B(O)O)[CH:40]=[CH:41][CH:42]=1.C(OCC)(=O)C>O.O1CCOCC1>[NH2:36][C:37]1[CH:42]=[C:41]([C:2]2[CH:3]=[C:4]3[C:8](=[C:9]([C:11]([NH2:13])=[O:12])[CH:10]=2)[NH:7][CH:6]=[C:5]3[CH:14]2[CH2:15][CH2:16][N:17]([S:20]([CH2:23][CH3:24])(=[O:22])=[O:21])[CH2:18][CH2:19]2)[CH:40]=[CH:39][CH:38]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 517367(3-Aminophenyl)boronic acid--sulfuric acid (1/1)HCID 113844275-bromo-3-[1-(ethanesulfonyl)-4-piperidinyl]-1H-indole-7-carboxamide

Product 1

HCID 57732687HCID 57732687, compoundYield 36.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

To a CEM microwave tube was added 5-bromo-3-[1-(ethylsulfonyl)-4-piperidinyl]-1H-indole-7-carboxamide (40 mg, 0.0965 mmol), potassium carbonate (80 mg, 0.578 mmol) and (3-aminophenyl)boronic acid sulfate (145 mg, 0.386 mmol). The mixture was taken up in water (1.2 mL) and dioxane (2.8 mL), and chloro-2-(dimethylaminomethyl)-ferrocen-1-yl-(dinorbornylphosphine)palladium(II) (1 mg, 0.002 mmol) was added. The mixture was then reacted in a CEM microwave for 10 min at 150° C. Ethyl acetate (2 mL) was added and the layers were separated. The aqueous layer was washed with ethyl acetate (1×2 mL). The organic layers were pooled, concentrated under a stream of nitrogen, and taken up in dimethyl sulfoxide (0.89 mL) and trifluoroacetic acid (0.15 mL). This solution of crude product was purified on an Agilent MDAP eluting with a linear gradient of 30% CH3CN/H2O (0.1% TFA) to 70% CH3CN/H2O (0.1% TFA) at 20 mL/min over 9 min. To the HPLC fraction containing product was added a solution of saturated K2CO3 (1 mL), a 1 M solution of sodium hydroxide (1 mL), and ethyl acetate (2 mL). The layers were separated and the aqueous layer was extracted with ethyl acetate (2×2 mL). The organic layers were pooled, filtered through a plug of magnesium sulfate, and concentrated under a stream of nitrogen to give 14.9 mg of the title compound (36%).

Workup

  1. customThe mixture was then reacted in a CEM microwave for 10 min at 150° C
  2. customthe layers were separated
  3. washThe aqueous layer was washed with ethyl acetate (1×2 mL)
  4. concentrationconcentrated under a stream of nitrogen
  5. customThis solution of crude product was purified on an Agilent MDAP
  6. washeluting with a linear gradient of 30% CH3CN/H2O (0.1% TFA) to 70% CH3CN/H2O (0.1% TFA) at 20 mL/min over 9 min
  7. additionTo the HPLC fraction containing product
  8. additionwas added a solution of saturated K2CO3 (1 mL)
  9. customThe layers were separated
  10. extractionthe aqueous layer was extracted with ethyl acetate (2×2 mL)
  11. filtrationfiltered through a plug of magnesium sulfate
  12. concentrationconcentrated under a stream of nitrogen

Sources & evidence

ORD record
ord-247c925715094d0fb11c99442a809d46
Source dataset
uspto-grants-2011_11
Patent number
US08063071B2

Reaction notes

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