Sodium hydride → 1-(2-Cyclopropyl-3-methylimidazo[1,2-a]pyridin-6-yl)-4-((2,4-difluorobenzyl)oxy)pyridin-2(1H)-one

HRID 2202863노트

반응식

HRID 2202863 반응식
[H-].[Na+].[CH:3]1([C:6]2[N:7]=[C:8]3[CH:13]=[CH:12][C:11]([N:14]4[CH:19]=[CH:18][C:17]([OH:20])=[CH:16][C:15]4=[O:21])=[CH:10][N:9]3[C:22]=2[CH3:23])[CH2:5][CH2:4]1.[F:24][C:25]1[CH:32]=[C:31]([F:33])[CH:30]=[CH:29][C:26]=1[CH2:27]Br>C1COCC1>[CH:3]1([C:6]2[N:7]=[C:8]3[CH:13]=[CH:12][C:11]([N:14]4[CH:19]=[CH:18][C:17]([O:20][CH2:27][C:26]5[CH:29]=[CH:30][C:31]([F:33])=[CH:32][C:25]=5[F:24])=[CH:16][C:15]4=[O:21])=[CH:10][N:9]3[C:22]=2[CH3:23])[CH2:5][CH2:4]1

참가 물질

5

반응물 3

HCID 24758Sodium hydrideHCID 902971-(Bromomethyl)-2,4-difluorobenzeneHCID 896902811-(2-Cyclopropyl-3-methylimidazo[1,2-a]pyridin-6-yl)-4-hydroxypyridin-2(1H)-one

생성물 1

HCID 896905191-(2-Cyclopropyl-3-methylimidazo[1,2-a]pyridin-6-yl)-4-((2,4-difluorobenzyl)oxy)pyridin-2(1H)-one수율 35%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매3회

실험 절차

To a stirred suspension of NaH (40% oil dispersion, 19 mg) in THF (6 ml) was added a solution of 1-(2-cyclopropyl-3-methylimidazo[1,2-a]pyridin-6-yl)-4-hydroxypyridin-2 (1H)-one (75 mg) in THF (1 ml) at 0° C., and then the mixture was stirred at room temperature for 30 min. 2,4-Difluorobenzyl bromide (67 mg) in THF (0.5 ml) was added, and the resulting mixture was stirred at room temperature for further 3 h followed by heating at reflux for 6 h. The reaction mixture was then cooled to room temperature and quenched with ice-water. The mixture was extracted with DCM, and the extract was washed with brine, dried over Na2SO4 and concentrated in vacuo. The crude product was purified by silica gel column chromatography (MeOH/DCM) to give the title compound (38 mg) as an off-white solid.

후처리

  1. stirringthe resulting mixture was stirred at room temperature for further 3 h
  2. temperatureby heating
  3. temperatureat reflux for 6 h
  4. temperatureThe reaction mixture was then cooled to room temperature
  5. customquenched with ice-water
  6. extractionThe mixture was extracted with DCM
  7. washthe extract was washed with brine
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated in vacuo
  10. customThe crude product was purified by silica gel column chromatography (MeOH/DCM)

출처 및 근거

ORD 기록
ord-694a898808c64a83a6b48e3d70002227
출처 데이터셋
uspto-grants-2016_06
특허 번호
US09365540B2

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