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

HRID 387387Notes

Reaction equation

HRID 387387 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].Br[C:33]1[S:37][C:36]([CH2:38][N:39]2[CH2:43][CH2:42][CH2:41][CH2:40]2)=[CH:35][CH:34]=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>[CH3:31][C:2]1([CH3:1])[CH2:7][CH:6]([C:8]2[C:16]3[C:11](=[C:12]([C:26]([NH2:28])=[O:27])[CH:13]=[C:14]([C:33]4[S:37][C:36]([CH2:38][N:39]5[CH2:43][CH2:42][CH2:41][CH2:40]5)=[CH:35][CH:34]=4)[CH:15]=3)[NH:10][CH:9]=2)[CH2:5][CH2:4][S:3]1(=[O:29])=[O:30]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 593327581-[(5-Bromo-2-thienyl)methyl]pyrrolidineHCID 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 593326893-(2,2-Dimethyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-5-[5-(1-pyrrolidinylmethyl)-2-thienyl]-1H-indole-7-carboxamideYield 22.5%

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), 1-[(5-bromo-2-thienyl)methyl]pyrrolidine (50 mg, 0.17 mmol), PdCl2(dppf)-CH2Cl2 adduct (20 mg, 0.024 mmol), and potassium carbonate (100 mg, 0.72 mmol) 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 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 concentrated. The residue was dissolved 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 concentrated. The product was further purified by trituration from diethyl ether to afford 18.6 mg of the title compound.

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. concentrationconcentrated
  7. dissolutionThe residue was dissolved in ˜3 mL of dmso
  8. filtrationfiltered through a syringe
  9. filtrationfilter
  10. customThe crude product was purified by ammonium hydroxide Gilson HPLC
  11. concentrationthe desired fractions were concentrated
  12. customThe product was further purified by trituration from diethyl ether

Sources & evidence

ORD record
ord-811a38b67e2144ebb0d0ed83c7219018
Source dataset
uspto-grants-2013_02
Patent number
US08372875B2

Reaction notes

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