Potassium Carbonate → HCID 59332752, compound

HRID 387375Notes

Reaction equation

HRID 387375 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.O1CCOCC1.[S:30]1[CH:34]=[CH:33][C:32](B(O)O)=[CH:31]1.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:32]4[CH:33]=[CH:34][S:30][CH:31]=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 581760Thiophene-3-boronic acidHCID 59332724HCID 59332724, compound

Product 1

HCID 59332752HCID 59332752, compoundYield 19.3%

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 (144 mg, 0.36 mmol) was placed in a microwave vial and dissolved with 1,4-dioxane (6 mL) and water (3 mL). 3-Thiopheneboronic acid (92 mg, 0.72 mmol) and K2CO3 (150 mg, 1.1 mmol) were added. Argon was bubbled in the mixture for 10 min with stirring. PdCl2(dppf) (21 mg, 0.29 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 DMSO (3 mL), and was purified on a Gilson HPLC. The desired fractions were concentrated, giving 28 mg (19%) 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 DMSO (3 mL)
  11. customwas purified on a Gilson HPLC
  12. concentrationThe desired fractions were concentrated

Sources & evidence

ORD record
ord-2a3745ee49b54588ae333816b07bab65
Source dataset
uspto-grants-2013_02
Patent number
US08372875B2

Reaction notes

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