Potassium Carbonate → 5-[5-(cyclopentylsulfonyl)-2-thienyl]-3-(2,2-dimethyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-1H-indole-7-carboxamide

HRID 656151Notes

Reaction equation

HRID 656151 reaction equation
[CH3:1][C:2]1([CH3:31])[CH2:7][CH:6]([C:8]2[C:16]3[C:11](=[C:12]([C:26]([NH2:28])=[O:27])[CH:13]=[C:14](B4OC(C)(C)C(C)(C)O4)[CH:15]=3)[NH:10][CH:9]=2)[CH2:5][CH2:4][S:3]1(=[O:30])=[O:29].[CH:32]1([S:37]([C:40]2[S:41][C:42](Br)=[CH:43][CH:44]=2)(=[O:39])=[O:38])[CH2:36][CH2:35][CH2:34][CH2:33]1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O.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].C(Cl)Cl>[CH:32]1([S:37]([C:40]2[S:41][C:42]([C:14]3[CH:15]=[C:16]4[C:11](=[C:12]([C:26]([NH2:28])=[O:27])[CH:13]=3)[NH:10][CH:9]=[C:8]4[CH:6]3[CH2:5][CH2:4][S:3](=[O:29])(=[O:30])[C:2]([CH3:1])([CH3:31])[CH2:7]3)=[CH:43][CH:44]=2)(=[O:39])=[O:38])[CH2:33][CH2:34][CH2:35][CH2:36]1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 46469162-Bromo-5-(cyclopentylsulfonyl)thiopheneHCID 593327993-(2,2-Dimethyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-7-carboxamide

Product 1

HCID 593325765-[5-(cyclopentylsulfonyl)-2-thienyl]-3-(2,2-dimethyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-1H-indole-7-carboxamide

Reagents, catalysts & solvents 3

HCID 178418807HCID 178418807, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

3-(2,2-Dimethyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-7-carboxamide (75 mg, 0.17 mmol), 5-bromo-2-thienyl cyclopentyl sulfone (60 mg, 0.20 mmol), PdCl2(dppf)-CH2Cl2 adduct (20 mg, 0.024 mmol, 0.15 eq), and potassium carbonate (100 mg, 0.72 mmol, 4.3 eq) were diluted in a mixture of 1,4-dioxane (3 mL) and water (1.5 mL) in a 2-5 mL microwave tube. The mixture was degassed by bubbling argon through for 5 minutes, then was heated in a biotage microwave at 100° C. for 5 minutes. The crude reaction mixture was filtered through a thiol SPE cartridge (polymer labs) to remove palladium, and was concentrated. The residue was re-diluted in ˜3 mL of dmso, and filtered through a syringe filter. The crude product was purified by ammonium hydroxide Gilson HPLC, and the desired fractions were evaporated to afford 5-[5-(cyclopentylsulfonyl)-2-thienyl]-3-(2,2-dimethyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-1H-indole-7-carboxamide as an off white solid (22.4 mg, 24%).

Workup

  1. customThe mixture was degassed
  2. customby bubbling argon through for 5 minutes
  3. customThe crude reaction mixture
  4. filtrationwas filtered through a thiol SPE cartridge (polymer labs)
  5. customto remove palladium
  6. concentrationwas concentrated
  7. additionThe residue was re-diluted in ˜3 mL of dmso
  8. filtrationfiltered through a syringe
  9. filtrationfilter
  10. customThe crude product was purified by ammonium hydroxide Gilson HPLC
  11. customthe desired fractions were evaporated

Sources & evidence

ORD record
ord-27abab81e54f46b99c9b27468d7c3760
Source dataset
uspto-grants-2011_12
Patent number
US08071584B2

Reaction notes

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