Potassium Carbonate → HCID 59332719, compound

HRID 656135Notes

Reaction equation

HRID 656135 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][CH:18]([CH3:20])[S:17](=[O:22])(=[O:21])[CH:16]([CH3:23])[CH2:15]1.[S:24]1[CH:28]=[CH:27][C:26](B(O)O)=[CH:25]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]>[CH3:20][CH:18]1[CH2:19][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:27]=[CH:28][S:24][CH:25]=4)[CH:3]=3)[NH:7][CH:6]=2)[CH2:15][CH:16]([CH3:23])[S:17]1(=[O:22])=[O:21]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 581760Thiophene-3-boronic acidHCID 59332769HCID 59332769, compound

Product 1

HCID 59332719HCID 59332719, compoundYield 101.4%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

5-bromo-3-(2,6-dimethyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-1H-indole-7-carboxamide (0.050 g, 0.125 mmol) and 3-thienylboronic acid (0.016 g, 0.125 mmol) was dissolved in a 6:1 solution of 1,4 dioxane (3 mL)/water (0.5 mL) in a 20 mL microwave reaction vessel. Potassium carbonate (0.087 g, 0.626 mmol, 5 eq) was added and the solution was degassed with Nitrogen. PdCl2(dppf)2 (0.016 g, 0.021 mmol, 0.17 eq) was added and the reaction was heated in a microwave at 100° C. for 20 min. The solution was passed through a StratoSphere SPE PL-Thiol MP SPE column to remove palladium and purified on Gilson preparative HPLC using Acetonitrile/Water with 0.1% TFA. The desired fractions were concentrated, giving 0.051 g of a mixture of diasteriomers and their respective enantiomers.

Workup

  1. customthe solution was degassed with Nitrogen
  2. customto remove palladium
  3. custompurified on Gilson preparative HPLC
  4. concentrationThe desired fractions were concentrated

Sources & evidence

ORD record
ord-a39140b87dc24b32b6477d0307999e29
Source dataset
uspto-grants-2011_12
Patent number
US08071584B2

Reaction notes

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