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

HRID 76386

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>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

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

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

Sources & evidence

ORD record: ord-bee8575046a648daae173e0b9e6482e5
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08835640B1

Linked notes

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