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

HRID 387388Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 387388
[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]([S:38]([N:41]2[CH2:45][CH2:44][CH2:43][CH2:42]2)(=[O:40])=[O:39])=[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>[CH3:1][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]([C:33]4[S:37][C:36]([S:38]([N:41]5[CH2:45][CH2:44][CH2:43][CH2:42]5)(=[O:39])=[O:40])=[CH:35][CH:34]=4)[CH:15]=3)[NH:10][CH:9]=2)[CH2:5][CH2:4][S:3]1(=[O:30])=[O:29]

Komponenten

7

Edukt 3

HCID 11430Potassium CarbonateHCID 8939391-[(5-Bromo-2-thienyl)sulfonyl]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

Produkt 1

HCID 593326763-(2,2-Dimethyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-5-[5-(1-pyrrolidinylsulfonyl)-2-thienyl]-1H-indole-7-carboxamideAusbeute 21,4 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418807HCID 178418807, VerbindungKatalysatorHCID 962WaterLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

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)sulfonyl]pyrrolidine (60 mg, 0.17 mmol, 1 eq), 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 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. The crude product was purified by ammonium hydroxide Gilson hplc, and the desired fractions were evaporated. The product was further purified by trituration from diethyl ether to afford 19.5 mg (21%) of the title compound.

Aufarbeitung

  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
  9. customThe crude product was purified by ammonium hydroxide Gilson
  10. customthe desired fractions were evaporated
  11. customThe product was further purified by trituration from diethyl ether

Quellen und Nachweise

ORD-Eintrag
ord-54fac488594841a2b0e59d8cdf1e6100
Quelldatensatz
uspto-grants-2013_02
Patentnummer
US08372875B2

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