Sodium Carbonate → HCID 57420250, compound

HRID 1431716Notes

Reaction equation

HRID 1431716 reaction equation
[NH2:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([N:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)[CH:3]=1.CC(C)([O-])C.[K+].Cl[C:23]1[C:32]2[C:27](=[CH:28][C:29]([F:34])=[CH:30][C:31]=2[F:33])[N:26]=[C:25]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][N:36]=2)[C:24]=1[CH3:41].C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C>[F:33][C:31]1[CH:30]=[C:29]([F:34])[CH:28]=[C:27]2[C:32]=1[C:23]([NH:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([N:10]3[CH2:15][CH2:14][O:13][CH2:12][CH2:11]3)[CH:3]=1)=[C:24]([CH3:41])[C:25]([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][N:36]=1)=[N:26]2

Participants

6

Reactant 4

HCID 10340Sodium CarbonateHCID 23665647Potassium tert-butoxideHCID 596310254-Chloro-5,7-difluoro-3-methyl-2-(pyridin-2-yl)quinolineHCID 67507962HCID 67507962, compound

Product 1

HCID 57420250HCID 57420250, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

A dry flask containing 4-amino-2-morpholinobenzonitrile (46.5 mg, 0.23 mmol) in dry DMF (2.0 mL) was cooled to 0° C., then potassium tert-butoxide (78.8 mg, 0.70 mmol) was added carefully in portions. The mixture was stirred at 0° C. for 15 minutes, then 4-chloro-5,7-difluoro-3-methyl-2-(pyridin-2-yl)quinoline (74.7 mg, 0.26 mmol) was added in portions. Upon complete addition, the mixture was warmed to 100° C. After 2.5 h, the reaction was cooled to rt then was carefully treated with 10% sodium carbonate solution. The black mixture was subsequently extracted five times with DCM:methanol (90:10). The organic extraction was then washed one time with brine and dried over anhydrous magnesium sulfate. After filtration and concentration, the residue was purified on silica gel (0-45% of a premixed solution of 89:9:1 DCM:methanol:ammonium hydroxide in DCM) to afford a yellow film that was further purified with HPLC (10-90% of 0.1% TFA acetonitrile solution in 0.1% TFA water solution.) The desired fractions were concd then diluted with EtOAc. After washing twice with satd aq. sodium bicarbonate solution and once with brine, the solvent was removed under reduced pressure to yield a light yellow solid as 4-(5,7-difluoro-3-methyl-2-(pyridin-2-yl)quinolin-4-ylamino)-2-morpholinobenzonitrile. 1H NMR (500 MHz, CDCl3) δ ppm 8.74 (1H, d, J=4.6 Hz), 7.97 (2H, m), 7.72 (1H, m), 7.47 (1H, d, J=8.3 Hz), 7.44 (1H, m), 7.11 (2H, m), 6.44 (2H, m), 3.96 (4H, m), 3.26 (4H, m), 2.24 (3H, s). Mass Spectrum (pos.) m/e: 458.0 (M+H)+.

Workup

  1. additionUpon complete addition
  2. temperaturethe mixture was warmed to 100° C
  3. waitAfter 2.5 h
  4. temperaturethe reaction was cooled to rt
  5. extractionThe black mixture was subsequently extracted five times with DCM:methanol (90:10)
  6. extractionThe organic extraction
  7. washwas then washed one time with brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. filtrationAfter filtration and concentration
  10. customthe residue was purified on silica gel (0-45% of a premixed solution of 89:9:1 DCM:methanol:ammonium hydroxide in DCM)
  11. customto afford a yellow film that
  12. customwas further purified with HPLC (10-90% of 0.1% TFA acetonitrile solution in 0.1% TFA water solution.) The desired fractions
  13. additionwere concd then diluted with EtOAc
  14. washAfter washing twice with satd aq. sodium bicarbonate solution and once with brine
  15. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-c2bb518c99b34002b4dfb3cb45cf4896
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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