Potassium Carbonate → HCID 59332804, compound

HRID 656114Notes

Reaction equation

HRID 656114 reaction equation
Br[CH:2]1[CH:10]([F:11])[C:9]([C:12]([NH2:14])=[O:13])=[C:8]2[C:4]([C:5]([CH:15]3[CH2:20][CH2:19][S:18](=[O:22])(=[O:21])[CH2:17][CH2:16]3)=[CH:6][NH:7]2)=[CH:3]1.[C:23]1(B(O)O)[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=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:21]=[S:18]1(=[O:22])[CH2:19][CH2:20][CH:15]([C:5]2[C:4]3[C:8](=[C:9]([C:12]([NH2:14])=[O:13])[C:10]([F:11])=[C:2]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[CH:3]=3)[NH:7][CH:6]=2)[CH2:16][CH2:17]1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 66827Phenylboronic AcidHCID 66746689HCID 66746689, compound

Product 1

HCID 59332804HCID 59332804, compoundYield 43%

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)-6-fluoro-5,6-dihydro-1H-indole-7-carboxamide (9.2 mg, 0.024 mmol), phenylboronic acid (5.73 mg, 0.047 mmol), and K2CO3 (9.75 mg, 0.071 mmol) was taken up in 1,4-dioxane (0.3 mL) and water (0.150 mL). The mixture was degassed with argon for 10 min, and PdCl2(dppf) (1.721 mg, 2.351 μmol) was added. The vial was sealed, and the reaction was heated in a Biotage microwave for 5 min at 100° C. on high absorption. The aqueous layer was removed via pipette, and the reaction mixture was filtered through a Stratosphere PL-Thio MP SPE cartridge (0.5 g), eluting with 1:1 DCM/MeOH (10 mL). The eluent was concentrated under a stream of nitrogen at 50° C., and the crude product was dissolved in DMSO (1.2 mL) and purified on a Gilson HPLC (XBridge C18 5 μm 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. and dried under high vacuum, giving 3.9 mg (43%) of the title compound.

Workup

  1. customThe mixture was degassed with argon for 10 min
  2. customThe vial was sealed
  3. customThe aqueous layer was removed via pipette
  4. filtrationthe reaction mixture was filtered through a Stratosphere PL-Thio MP SPE cartridge (0.5 g)
  5. washeluting with 1:1 DCM/MeOH (10 mL)
  6. concentrationThe eluent was concentrated under a stream of nitrogen at 50° C.
  7. dissolutionthe crude product was dissolved in DMSO (1.2 mL)
  8. custompurified on a Gilson HPLC (XBridge
  9. wash5 μm OBD 19×100 mm preparatory column), eluting at 15 mL/min with a linear gradient
  10. concentrationThe desired fractions were concentrated under a stream of nitrogen at 50° C.
  11. customdried under high vacuum

Sources & evidence

ORD record
ord-0978ccf5f46c484d8acfde47ec52b6c7
Source dataset
uspto-grants-2011_12
Patent number
US08071584B2

Reaction notes

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