Potassium Carbonate → HCID 25072549, compound

HRID 387376Notes

Reaction equation

HRID 387376 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][S:17](=[O:21])(=[O:20])[C:16]([CH3:23])([CH3:22])[CH2:15]1.[O:24]1[CH2:29][CH2:28]O[CH2:26][CH2:25]1.O1C=CC(B(O)O)=C1.C([O-])([O-])=O.[K+].[K+]>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].O>[CH3:22][C:16]1([CH3:23])[CH2:15][CH:14]([C:5]2[C:4]3[C:8](=[C:9]([C:11]([NH2:13])=[O:12])[CH:10]=[C:2]([C:26]4[CH:28]=[CH:29][O:24][CH:25]=4)[CH:3]=3)[NH:7][CH:6]=2)[CH2:19][CH2:18][S:17]1(=[O:21])=[O:20]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 2734358Furan-3-boronic acidHCID 59332724HCID 59332724, compound

Product 1

HCID 25072549HCID 25072549, compoundYield 26%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

5-Bromo-3-(2,2-dimethyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-1H-indole-7-carboxamide (80 mg, 0.20 mmol) was placed in a microwave vial and dissolved with 1,4-dioxane (2 mL) and water (1 ml). 3-Furanylboronic acid (44.8 mg, 0.401 mmol) and K2CO3 (83 mg, 0.60 mmol) were added. Argon was bubbled in the mixture for 10 min with stirring. PdCl2(dppf) (4.83 mg, 0.01 mmol) was added, and argon was bubbled another 10 min. The vial is sealed and heated in a microwave for 5 min at 100° C. on high absorption. The reaction was evaporated to remove most of the dioxane. The residue was partitioned between ethyl acetate and water. The layers were separated, the organic layer was dried (MgSO4), and the solvent was removed under vacuum. The residue was dissolved in the minimum amount of MeOH and EtOAc, and was run through a thiol-SPE cartridge eluting with 2 mL of MeOH. The solvent was removed under vacuum, and the residue was dissolved in 1-2 mL of DMSO, and purified on a Gilson HPLC. The desired fractions were concentrated, giving 22 mg (26%) of the title compound.

Workup

  1. customArgon was bubbled in the mixture for 10 min
  2. customargon was bubbled another 10 min
  3. customThe vial is sealed
  4. customThe reaction was evaporated
  5. customto remove most of the dioxane
  6. customThe residue was partitioned between ethyl acetate and water
  7. customThe layers were separated
  8. dry with materialthe organic layer was dried (MgSO4)
  9. customthe solvent was removed under vacuum
  10. dissolutionThe residue was dissolved in the minimum amount of MeOH and EtOAc
  11. washeluting with 2 mL of MeOH
  12. customThe solvent was removed under vacuum
  13. dissolutionthe residue was dissolved in 1-2 mL of DMSO
  14. custompurified on a Gilson HPLC
  15. concentrationThe desired fractions were concentrated

Sources & evidence

ORD record
ord-9d1db4ad90c8476a9c0dcf6fd529d2e2
Source dataset
uspto-grants-2013_02
Patent number
US08372875B2

Reaction notes

Loading…