Potassium Carbonate → HCID 67375520, compound

HRID 525207Notes

Reaction equation

HRID 525207 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([CH2:13][C@@H:14]3[CH2:18][CH2:17][N:16]([C:19]([CH:21]4[CH2:23][CH2:22]4)=[O:20])[CH2:15]3)=[N:11][NH:10][C:9]2=[O:24])=[CH:4][CH:3]=1.[C:25]1(B(O)O)[C:34]2[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=2)[CH:28]=[CH:27][CH:26]=1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.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].ClCCl>[CH:21]1([C:19]([N:16]2[CH2:17][CH2:18][C@@H:14]([CH2:13][C:12]3[N:8]([C:5]4[CH:6]=[CH:7][C:2]([C:33]5[C:34]6[C:29](=[CH:28][CH:27]=[CH:26][CH:25]=6)[CH:30]=[CH:31][CH:32]=5)=[CH:3][CH:4]=4)[C:9](=[O:24])[NH:10][N:11]=3)[CH2:15]2)=[O:20])[CH2:23][CH2:22]1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 2545321-Naphthaleneboronic acidHCID 673755254-(4-bromophenyl)-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one

Product 1

HCID 67375520HCID 67375520, compoundYield 56%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

A solution of 4-(4-bromophenyl)-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one (0.256 mmol) in dioxane (1.5 mL) was treated with 1-naphthalenylboronic acid (0.281 mmol), dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II)-dichloromethane adduct (10 mg), and 2M aq potassium carbonate (0.767 mmol). The reaction mixture was purged with nitrogen, sealed, and irradiated in a microwave (Biotage Initiator) at 150° C. for 15 min. The reaction mixture was cooled to room temperature and was diluted with water (50 mL). The aqueous layer was acidified to pH˜4 using 1N aq HCl and was extracted with dichloromethane. The organic layer was treated with Si-Thiol (Silicycle, 20 mg), dried over magnesium sulfate, filtered, and concentrated in vacuo. The crude residue was purified by reverse phase HPLC (30-60% acetonitrile w/0.1% TFA/water w/0.1% TFA). The product fractions from the HPLC were combined, adjusted to pH˜5 with the addition of saturated aq sodium bicarbonate, and extracted with dichloromethane. The organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo to afford the title compound as an amorphous white solid (56%). MS(ES)+ m/e 439.2 [M+H]+.

Workup

  1. customThe reaction mixture was purged with nitrogen
  2. customsealed
  3. customirradiated in a microwave (Biotage Initiator) at 150° C. for 15 min
  4. additionwas diluted with water (50 mL)
  5. extractionwas extracted with dichloromethane
  6. additionThe organic layer was treated with Si-Thiol (Silicycle, 20 mg)
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe crude residue was purified by reverse phase HPLC (30-60% acetonitrile w/0.1% TFA/water w/0.1% TFA)
  11. additionadjusted to pH˜5 with the addition of saturated aq sodium bicarbonate
  12. extractionextracted with dichloromethane
  13. dry with materialThe organic layer was dried over magnesium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-5485c7493cc34f58a83663c7627db58d
Source dataset
uspto-grants-2016_05
Patent number
US09340529B2

Reaction notes

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