Potassium Carbonate → HCID 71565882, compound

HRID 922782Notes

Reaction equation

HRID 922782 reaction equation
[CH:1]1([CH:4]2[S:9][CH2:8][CH2:7][NH:6][CH2:5]2)[CH2:3][CH2:2]1.C([O-])([O-])=O.[K+].[K+].Br[CH2:17][C:18]1[CH:27]=[C:26]2[C:21]([C:22]([C:30]3[CH:31]=[N:32][N:33]([CH3:35])[CH:34]=3)=[CH:23][C:24]([C:28]#[N:29])=[N:25]2)=[CH:20][CH:19]=1>CC#N.CCOC(C)=O>[CH:1]1([CH:4]2[CH2:5][N:6]([CH2:17][C:18]3[CH:27]=[C:26]4[C:21]([C:22]([C:30]5[CH:31]=[N:32][N:33]([CH3:35])[CH:34]=5)=[CH:23][C:24]([C:28]#[N:29])=[N:25]4)=[CH:20][CH:19]=3)[CH2:7][CH2:8][S:9]2)[CH2:3][CH2:2]1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 89543564HCID 89543564, compoundHCID 89545156HCID 89545156, compound

Product 1

HCID 71565882HCID 71565882, compoundYield 45.2%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of crude 2-cyclopropylthiomorpholine (4-14, 100 mg, 0.698 mmol) in CH3CN (3 ml) was added K2CO3 (289 mg, 2.094 mmol) then 7-(bromomethyl)-4-(1-methyl-1H-pyrazol-4-yl)quinoline-2-carbonitrile (251 mg, 0.768 mmol) all at once as solid. The resulting mixture was heated to 60° C. overnight. The mixture was cooled to rt, diluted with EtOAc, filtered through a pad of Celite washing with EtOAc, and concentrated. The crude product was subjected to silica gel chromatography (25 g, 0-100% EtOAc/hexanes, 10 minute gradient) to afford 7-((2-Cyclopropylthiomorpholino)methyl)-4-(1-methyl-1H-pyrazol-4-yl)quinoline-2-carbonitrile (4-15, 123 mg, 45%) as a light orange foam. 1H NMR (399 MHz, CDCl3): δ 8.19 (d, J=8.7 Hz, 1 μl); 8.09 (s, 1 μl); 7.85 (s, 1 μl); 7.77 (s, 1H); 7.71 (d, J=8.8 Hz, 1H); 7.61 (s, 1H); 4.07 (s, 3H); 3.85-3.70 (m, 2 μl); 3.16 (dd, J=11.6, 2.7 Hz, 1H); 3.01 (d, J=11.6 Hz, 1H); 2.83 (ddd, J=13.4, 10.6, 2.7 Hz, 1H); 2.61-2.53 (m, 1H); 2.45-2.34 (m, 2H); 2.20-2.13 (m, 1H); 0.88-0.80 (m, 1H); 0.61-0.44 (m, 2H); 0.36-0.27 (m, 1H); 0.23-0.16 (m, 1H).

Workup

  1. temperatureThe mixture was cooled to rt
  2. filtrationfiltered through a pad of Celite
  3. washwashing with EtOAc
  4. concentrationconcentrated
  5. customwas subjected to silica gel chromatography (25 g, 0-100% EtOAc/hexanes, 10 minute gradient)

Sources & evidence

ORD record
ord-f41e5cd630c548469d62b976c9aa4028
Source dataset
uspto-grants-2016_03
Patent number
US09278960B2

Reaction notes

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