Sodium Carbonate → N-(2-(1-cyclohexen-1-yl)-5-(4-morpholinyl)-3-pyridinyl)-5,7-difluoro-3-methyl-2-(2-pyridinyl)-4-quinolinamine

HRID 1431363노트

반응식

HRID 1431363 반응식
Br[C:2]1[CH:3]=[C:4]([NH2:14])[C:5]([C:8]2[CH2:13][CH2:12][CH2:11][CH2:10][CH:9]=2)=[N:6][CH:7]=1.[H-].[Na+].Cl[C:18]1[C:27]2[C:22](=[CH:23][C:24]([F:29])=[CH:25][C:26]=2[F:28])[N:21]=[C:20]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][N:31]=2)[C:19]=1[CH3:36].[C:37](=[O:40])([O-])[O-].[Na+].[Na+]>CN(C=O)C>[C:8]1([C:5]2[C:4]([NH:14][C:18]3[C:27]4[C:22](=[CH:23][C:24]([F:29])=[CH:25][C:26]=4[F:28])[N:21]=[C:20]([C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][N:31]=4)[C:19]=3[CH3:36])=[CH:3][C:2]([N:6]3[CH2:7][CH2:37][O:40][CH2:4][CH2:5]3)=[CH:7][N:6]=2)[CH2:13][CH2:12][CH2:11][CH2:10][CH:9]=1

참가 물질

6

반응물 4

HCID 10340Sodium CarbonateHCID 24758Sodium hydrideHCID 596310254-Chloro-5,7-difluoro-3-methyl-2-(pyridin-2-yl)quinolineHCID 596312915-Bromo-2-cyclohexenylpyridin-3-amine

생성물 1

HCID 67507730N-(2-(1-cyclohexen-1-yl)-5-(4-morpholinyl)-3-pyridinyl)-5,7-difluoro-3-methyl-2-(2-pyridinyl)-4-quinolinamine

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

반응 조건

온도
0 °C

실험 절차

A dry flask containing 5-bromo-2-cyclohexenylpyridin-3-amine (0.19 g, 0.76 mmol) in dry DMF (5.0 mL) was cooled to 0° C., then sodium hydride, 60% dispersion in mineral oil (0.061 g, 1.53 mmol) was added carefully in portions. The mixture was stirred at 0° C. for 15 min, then 4-chloro-5,7-difluoro-3-methyl-2-(pyridin-2-yl)quinoline (0.26 g, 0.91 mmol) was added in portions. Upon complete addition, the mixture was warmed to 70° C. After 18 h, the incomplete reaction was cooled to rt then was carefully treated with 10% sodium carbonate solution. The black mixture was subsequently extracted five times with DCM:MeOH (90:10). The organic extraction was then washed one time with brine and dried over anhydrous magnesium sulfate. After filtration and concentration, the black residue was treated with MeOH and placed on the rotovap. (without vac.) in a 45° C. water bath. After 30 min, the solid was filtered and rinsed twice with MeOH to afford a tan solid as N-(2-(1-cyclohexen-1-yl)-5-(4-morpholinyl)-3-pyridinyl)-5,7-difluoro-3-methyl-2-(2-pyridinyl)-4-quinolinamine. 1H NMR (500 MHz, DMSO-d6) δ ppm 8.72 (1H, d, J=3.9 Hz), 8.15 (3H, m), 7.89 (1H, d, J=7.8 Hz), 7.68 (1H, d, J=9.0 Hz), 7.53 (1H, ddd, J=7.6, 4.9, 1.2 Hz), 7.46 (1H, m.), 7.01 (1H, s), 5.92 (1H, m.), 2.37 (1H, dd, J=3.5, 1.8 Hz), 2.16 (3H, s), 1.99 (2H, m), 1.63 (2H, m), 1.46 (2H, m.).

후처리

  1. additionUpon complete addition
  2. temperaturethe mixture was warmed to 70° C
  3. waitAfter 18 h
  4. customthe incomplete reaction
  5. temperaturewas cooled to rt
  6. extractionThe black mixture was subsequently extracted five times with DCM:MeOH (90:10)
  7. extractionThe organic extraction
  8. washwas then washed one time with brine
  9. dry with materialdried over anhydrous magnesium sulfate
  10. filtrationAfter filtration and concentration
  11. additionthe black residue was treated with MeOH
  12. customin a 45° C.
  13. waitAfter 30 min
  14. filtrationthe solid was filtered
  15. washrinsed twice with MeOH

출처 및 근거

ORD 기록
ord-ddfdc1e759f14bb3bf8285c7f8d075db
출처 데이터셋
uspto-grants-2015_01
특허 번호
US08940724B2

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