Potassium Carbonate → HCID 66746251, compound

HRID 656156Notes

Reaction equation

HRID 656156 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.O1CCOCC1.[S:31]1[CH:35]=[CH:34][C:33](B(O)O)=[CH:32]1.C([O-])([O-])=O.[K+].[K+]>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>[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:33]4[CH:34]=[CH:35][S:31][CH:32]=4)[CH:3]=3)[NH:7][CH:6]=2)[CH2:19][CH2:18][S:17]1(=[O:21])=[O:20])[CH3:24]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 581760Thiophene-3-boronic acidHCID 66746098HCID 66746098, compound

Product 1

HCID 66746251HCID 66746251, compoundYield 26.7%

Reagents, catalysts & solvents 2

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

Procedure

5-Bromo-3-[cis-2-(1-methylethyl)-1,1-dioxidotetrahydro-2H-thiopyran-4-yl]-1H-indole-7-carboxamide (37 mg, 0.090 mmol) was placed in a microwave vial and dissolved with 1,4-Dioxane (1 mL) and Water (0.500 mL). Thiophene 3-boronic acid (22.91 mg, 0.179 mmol) and K2CO3 (37.1 mg, 0.269 mmol) were added. Argon was bubbled in the mixture for 10 mins, stirring. PdCl2(dppf) (3.45 mg, 7.16 μmol) was added, and argon was bubbled another 10 mins. The vial was sealed and put under microwave 5 mins at 100° C. with high absorption parameter. The mixture was run through a thiol-SPE column, eluting with methanol. The collected solution was concentrated in vacuo. The brown solid was dissolved in 2-3 mL of DMSO, and run through the ammonium Gilson, in 3 injections to afford 10 mg of the title compound. The cis stereochemistry of the product was confirmed by a 1H NMR NOE study.

Workup

  1. customArgon was bubbled in the mixture for 10 mins
  2. customargon was bubbled another 10 mins
  3. customThe vial was sealed
  4. washeluting with methanol
  5. concentrationThe collected solution was concentrated in vacuo
  6. dissolutionThe brown solid was dissolved in 2-3 mL of DMSO

Sources & evidence

ORD record
ord-e4b4bf4cc6ec4c79adac57d8db7d9ee0
Source dataset
uspto-grants-2011_12
Patent number
US08071584B2

Reaction notes

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