Cesium carbonate → 4-[6-{3-[(2R)-2-methylpyrrolidin-1-yl]propoxy}-2-oxo-3,4-dihydroquinolin-1(2H)-yl]benzonitrile

HRID 1913880Notes

Reaction equation

[CH3:1][C@@H:2]1[CH2:6][CH2:5][CH2:4][N:3]1[CH2:7][CH2:8][CH2:9][O:10][C:11]1[CH:12]=[C:13]2[C:18](=[CH:19][CH:20]=1)[NH:17][C:16](=[O:21])[CH2:15][CH2:14]2.I[C:23]1[CH:30]=[CH:29][C:26]([C:27]#[N:28])=[CH:25][CH:24]=1.CN[C@@H]1CCCC[C@H]1NC.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O.O.[Cu](I)I>[CH3:1][C@@H:2]1[CH2:6][CH2:5][CH2:4][N:3]1[CH2:7][CH2:8][CH2:9][O:10][C:11]1[CH:12]=[C:13]2[C:18](=[CH:19][CH:20]=1)[N:17]([C:23]1[CH:30]=[CH:29][C:26]([C:27]#[N:28])=[CH:25][CH:24]=1)[C:16](=[O:21])[CH2:15][CH2:14]2

Participants

Conditions

Temperature: 100 °C

Procedure

A suspension of (2R)-6-[3-(2-methylpyrrolidin-1-yl)propoxy]-3,4-dihydroquinolin-2(1H)-one prepared in Example 1-(2) (0.20 g), 4-iodobenzonitrile (0.18 g), rac-trans-N,N′-dimethylcyclohexane-1,2-diamine (0.041 g), copper iodide (0.013 g) and cesium carbonate (0.45 g) in N,N-dimethylformamide (2 mL) was stirred at 100° C. for 16 hours. The reaction mixture was diluted with water and extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by preparative TLC (on a single plate of 2 mm thickness, developing solvent: chloroform/methanol=9/1) and NH-type preparative TLC (on two plates of 0.25 mm thickness, developing solvent: n-hexane/ethyl acetate=1/1) to give the titled compound (0.062 g, 23%) as a light-brown amorphous substance.

Workup

extractionextracted with chloroform
dry with materialThe organic layer was dried over anhydrous sodium sulfate
concentrationconcentrated under reduced pressure
customThe resulting residue was purified by preparative TLC (on a single plate of 2 mm thickness

Sources & evidence

ORD record: ord-43555495dabb41f2bd72216f8875f38a
Source dataset: uspto-grants-2013_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08609847B2

Reaction notes

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