Dichloromethane → 3-(5-(5-Acetylthiophen-2-yl)nicotinoyl)-1-methylpyrrolidin-2-one

HRID 407168

Reaction equation

HRID 407168 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([CH:16]=1)[C:7]([CH:9]1[CH2:13][CH2:12][N:11]([CH3:14])[C:10]1=[O:15])=[O:8].[C:17]([C:20]1[S:24][C:23](B(O)O)=[CH:22][CH:21]=1)(=[O:19])[CH3:18].C(Cl)Cl.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.O1CCOCC1.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[C:17]([C:20]1[S:24][C:23]([C:2]2[CH:3]=[N:4][CH:5]=[C:6]([CH:16]=2)[C:7]([CH:9]2[CH2:13][CH2:12][N:11]([CH3:14])[C:10]2=[O:15])=[O:8])=[CH:22][CH:21]=1)(=[O:19])[CH3:18]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 4143377(5-Acetylthiophen-2-yl)boronic acidHCID 140613713-(5-Bromopyridine-3-carbonyl)-1-methylpyrrolidin-2-one

Product 1

HCID 715701183-(5-(5-Acetylthiophen-2-yl)nicotinoyl)-1-methylpyrrolidin-2-oneYield 50%

Reagents, catalysts & solvents 2

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 21840791Dioxane tolueneSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of 3-(5-bromonicotinoyl)-1-methylpyrrolidin-2-one 3 (1 equiv), 5-Acetyl-2-thiopheneboronic acid (1.2 equiv), 1,1′-bis(diphenylphosphino)ferrocene]dichloro palladium(II) complex with DCM (0.1 equiv) and 2M Na2CO3 (4 equiv) in toluene/1,4-dioxane (4:1, 15 volumes) was degassed and filled with nitrogen. Then the reaction mixture was heated to 85° C. and maintained for 2 h. After completion of the reaction filtered through Celite bed and washed with ethyl acetate. The combined organic layer was dried over with anhydrous sodium sulfate, filtered and concentrated under reduced pressure to obtain crude residue which was purified by silica-gel column chromatography using 2% MeOH/DCM as an eluent to afford 50% yield of titled compound.

Workup

  1. customwas degassed
  2. additionfilled with nitrogen
  3. temperaturemaintained for 2 h
  4. filtrationAfter completion of the reaction filtered through Celite bed
  5. washwashed with ethyl acetate
  6. dry with materialThe combined organic layer was dried over with anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customto obtain crude residue which
  10. customwas purified by silica-gel column chromatography

Sources & evidence

ORD record
ord-bbe03d7274b04b19b844bded081d50a4
Source dataset
uspto-grants-2014_06
Patent number
US08754228B2

Linked notes

Loading…