Potassium Carbonate → HCID 59332653, compound

HRID 656152Notes

Reaction equation

HRID 656152 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[C@@H:14]1[CH2:19][CH2:18][S:17](=[O:21])(=[O:20])[C@@H:16]([CH:22]([CH3:24])[CH3:23])[CH2:15]1.[C:25]1(B(O)O)[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O.CS(C)=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]>[CH3:23][CH:22]([C@H:16]1[CH2:15][C@H:14]([C:5]2[C:4]3[C:8](=[C:9]([C:11]([NH2:13])=[O:12])[CH:10]=[C:2]([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)[CH:3]=3)[NH:7][CH:6]=2)[CH2:19][CH2:18][S:17]1(=[O:21])=[O:20])[CH3:24]

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 66827Phenylboronic AcidHCID 66746207HCID 66746207, compound

Product 1

HCID 59332653HCID 59332653, compoundYield 26.4%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

(racemic)-5-Bromo-3-[trans-2-(1-methylethyl)-1,1-dioxidotetrahydro-2H-thiopyran-4-yl]-1H-indole-7-carboxamide (65 mg, 0.157 mmol) was placed in a microwave vial and dissolved in 1,4-dioxane (2 mL) and water (1.000 mL). Phenylboronic acid (19.17 mg, 0.157 mmol) and K2CO3 (65.2 mg, 0.472 mmol) were added. Argon was bubbled in the mixture for 10 min, and then PdCl2(dppf) (6.07 mg, 0.013 mmol) was added, and argon was bubbled another 10 min. The vial was sealed and put under microwave 5 mins at 100° C. with high absorption parameter. The crude was run through a thiol-SPE cartridge eluting with methanol (2 mL) and the treated solution was evaporated to remove the biggest part of dioxane and methanol. The resulting mixture was partitioned between ethyl acetate and water. The organic layer was dried (MgSO4) and solvent removed in vacuo to give crude material which was dissolved in 1-2 mL of DMSO filtered through a syringe filter (Acrodisc CR 13 mm; 45 um PTFE filter), and run through the ammonium Gilson eluting with 35% to 90% organic in 15 min. The product was isolated to afford 17 mg 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 was sealed
  4. washeluting with methanol (2 mL)
  5. customthe treated solution was evaporated
  6. customto remove the biggest part of dioxane and methanol
  7. customThe resulting mixture was partitioned between ethyl acetate and water
  8. dry with materialThe organic layer was dried (MgSO4) and solvent
  9. customremoved in vacuo
  10. customto give crude material which
  11. filtrationfiltered through a syringe
  12. filtrationfilter
  13. filtration(Acrodisc CR 13 mm; 45 um PTFE filter)
  14. washeluting with 35% to 90% organic in 15 min
  15. customThe product was isolated

Sources & evidence

ORD record
ord-9895d437ecca40b0a72c0bb71e624bb7
Source dataset
uspto-grants-2011_12
Patent number
US08071584B2

Reaction notes

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