Potassium Carbonate → HCID 59332749, compound

HRID 387353Notes

Reaction equation

HRID 387353 reaction equation
Br[C:2]1[C:3]([F:22])=[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.[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:20]=[S:17]1(=[O:21])[CH2:18][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:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[C:3]=3[F:22])[NH:7][CH:6]=2)[CH2:15][CH2:16]1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 66827Phenylboronic AcidHCID 59332670HCID 59332670, compound

Product 1

HCID 59332749HCID 59332749, compoundYield 70%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
130 °C

Procedure

A mixture of 5-bromo-3-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-4-fluoro-1H-indole-7-carboxamide (15 mg, 0.039 mmol), phenylboronic acid (9.40 mg, 0.077 mmol), and K2CO3 (15.98 mg, 0.116 mmol) was taken up in 1,4-dioxane (0.2 mL) and water (0.100 mL). The mixture was degassed with argon for 10 min, and PdCl2(dppf) (2.82 mg, 3.85 μmol) was added. The vial was sealed, and the reaction was heated in a Biotage microwave for 30 min at 130° 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 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. and dried under high vacuum, giving 10.4 mg (70%) 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 mm 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-5dc10d681e8d4c0184a9ca683c0d1604
Source dataset
uspto-grants-2013_02
Patent number
US08372875B2

Reaction notes

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