Potassium Carbonate → HCID 59332767, compound

HRID 656084Notes

Reaction equation

HRID 656084 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])[CH2:16][CH2:15]1.[O:22]1[C:26]2[CH:27]=[CH:28][C:29](B(O)O)=[CH:30][C:25]=2[CH2:24][CH2:23]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]>[O:22]1[C:26]2[CH:27]=[CH:28][C:29]([C:2]3[CH:3]=[C:4]4[C:8](=[C:9]([C:11]([NH2:13])=[O:12])[CH:10]=3)[NH:7][CH:6]=[C:5]4[CH:14]3[CH2:19][CH2:18][S:17](=[O:21])(=[O:20])[CH2:16][CH2:15]3)=[CH:30][C:25]=2[CH2:24][CH2:23]1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 2773380(2,3-Dihydro-1-benzofuran-5-yl)boronic acidHCID 593327575-Bromo-3-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-1H-indole-7-carboxamide

Product 1

HCID 59332767HCID 59332767, compoundYield 20.5%

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

A mixture of 5-bromo-3-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-1H-indole-7-carboxamide (30 mg, 0.081 mmol), 2,3-dihydro-1-benzofuran-5-ylboronic acid (26.5 mg, 0.162 mmol), and K2CO3 (33.7 mg, 0.242 mmol) in 1,4-dioxane (0.36 mL) and water (0.180 mL) was degassed in a Biotage microwave vial for 10 min. PdCl2(dppf) (5.91 mg, 8.08 μmol) was added, the vial was sealed, and the reaction was heated at 100° C. (bath temp) for 5 min in a Biotage microwave oven at high absorption. EtOAc (3 mL) and water (1 mL) were added, the layers were separated, and the aqueous layer was extracted with EtOAc (4×2 mL). The combined organic layers were washed with saturated NaCl (1×2 mL), dried (Na2SO4), and concentrated under a stream of nitrogen at 50° C. The crude product was dissolved in DMSO (1.2 mL), filtered through a 0.2 mm acrodisc, and purified on a Gilson HPLC (XBridge C18 5 mm OBD 19×100 mm preparatory column), eluting at 15 mL/min with a linear gradient running from 20% CH3CN/H2O (0.1% NH4OH) to 70% CH3CN/H2O (0.1% NH4OH) over 18 min. The desired fractions were concentrated under a stream of nitrogen at 50° C., giving 6.8 mg (20%) of the title compound.

Workup

  1. customwas degassed in a Biotage microwave vial for 10 min
  2. customthe vial was sealed
  3. customat high absorption
  4. additionEtOAc (3 mL) and water (1 mL) were added
  5. customthe layers were separated
  6. extractionthe aqueous layer was extracted with EtOAc (4×2 mL)
  7. washThe combined organic layers were washed with saturated NaCl (1×2 mL)
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated under a stream of nitrogen at 50° C
  10. dissolutionThe crude product was dissolved in DMSO (1.2 mL)
  11. filtrationfiltered through a 0.2 mm acrodisc, and
  12. custompurified on a Gilson HPLC (XBridge
  13. wash5 mm OBD 19×100 mm preparatory column), eluting at 15 mL/min with a linear gradient
  14. concentrationThe desired fractions were concentrated under a stream of nitrogen at 50° C.

Sources & evidence

ORD record
ord-277aa8275b1147debf950e2169b5b87b
Source dataset
uspto-grants-2011_12
Patent number
US08071584B2

Reaction notes

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