Potassium Carbonate → 5-{[(3S)-1-acetyl-3-pyrrolidinyl]methyl}-4-[4-(7-quinolinyl)phenyl]-2,4-dihydro-3H-1,2,4-triazol-3-one

HRID 525241Notes

Reaction equation

HRID 525241 reaction equation
[C:1]([N:4]1[CH2:8][CH2:7][C@@H:6]([CH2:9][C:10]2[N:11]([C:16]3[CH:21]=[CH:20][C:19](Br)=[CH:18][CH:17]=3)[C:12](=[O:15])[NH:13][N:14]=2)[CH2:5]1)(=[O:3])[CH3:2].CC1(C)C(C)(C)OB([C:31]2[CH:40]=[C:39]3[C:34]([CH:35]=[CH:36][CH:37]=[N:38]3)=[CH:33][CH:32]=2)O1.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>[C:1]([N:4]1[CH2:8][CH2:7][C@@H:6]([CH2:9][C:10]2[N:11]([C:16]3[CH:21]=[CH:20][C:19]([C:31]4[CH:40]=[C:39]5[C:34]([CH:35]=[CH:36][CH:37]=[N:38]5)=[CH:33][CH:32]=4)=[CH:18][CH:17]=3)[C:12](=[O:15])[NH:13][N:14]=2)[CH2:5]1)(=[O:3])[CH3:2]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 592961167-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)QuinolineHCID 673757745-{[(3S)-1-acetyl-3-pyrrolidinyl]methyl}-4-(4-bromophenyl)-2,4-dihydro-3H-1,2,4-triazol-3-one

Product 1

HCID 673540705-{[(3S)-1-acetyl-3-pyrrolidinyl]methyl}-4-[4-(7-quinolinyl)phenyl]-2,4-dihydro-3H-1,2,4-triazol-3-one

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

A solution of 5-{[(3S)-1-acetyl-3-pyrrolidinyl]methyl}-4-(4-bromophenyl)-2,4-dihydro-3H-1,2,4-triazol-3-one (0.211 mmol) in dioxane (2 mL) was treated with 7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinoline (0.216 mmol), dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II)-dichloromethane adduct (20 mg), and 2M aq potassium carbonate (1 mL). The reaction mixture was purged with nitrogen, sealed, and stirred at 110° C. for 1 h. The reaction mixture was cooled to room temperature, diluted with water, neutralized with the dropwise addition of 6N aq HCl, and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. Reverse phase HPLC (10-70% acetonitrile/water+0.1% NH4OH) was utilized to purify the title compound (29 mg, 33%). MS(ES)+ m/e 413.8 [M+H]+.

Workup

  1. customThe reaction mixture was purged with nitrogen
  2. customsealed
  3. temperatureThe reaction mixture was cooled to room temperature
  4. additiondiluted with water
  5. additionneutralized with the dropwise addition of 6N aq HCl
  6. extractionextracted with ethyl acetate
  7. dry with materialThe organic layer was dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto purify the title compound (29 mg, 33%)

Sources & evidence

ORD record
ord-4452e4332bdd4271a4ea93e76ded4053
Source dataset
uspto-grants-2016_05
Patent number
US09340529B2

Reaction notes

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