1,1'-Carbonyldiimidazole → 3-[({[8-(Cyclohexylmethoxy)-2-methylimidazo[1,2-a]pyridin-3-yl]carbonyl}amino)sulfonyl]propyl acetate

HRID 64476

반응식

HRID 64476 반응식
[CH:1]1([CH2:7][O:8][C:9]2[C:10]3[N:11]([C:15]([C:19]([OH:21])=O)=[C:16]([CH3:18])[N:17]=3)[CH:12]=[CH:13][CH:14]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(N1C=CN=C1)(N1C=CN=C1)=O.[C:34]([O:37][CH2:38][CH2:39][CH2:40][S:41]([NH2:44])(=[O:43])=[O:42])(=[O:36])[CH3:35].C1CCN2C(=NCCC2)CC1>C1COCC1.C(OCC)(=O)C.O>[C:34]([O:37][CH2:38][CH2:39][CH2:40][S:41]([NH:44][C:19]([C:15]1[N:11]2[CH:12]=[CH:13][CH:14]=[C:9]([O:8][CH2:7][CH:1]3[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]3)[C:10]2=[N:17][C:16]=1[CH3:18])=[O:21])(=[O:42])=[O:43])(=[O:36])[CH3:35]

참가 물질

8

반응물 4

HCID 682631,1'-CarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 106074883-(Aminosulfonyl)propyl acetateHCID 711084908-(Cyclohexylmethoxy)-2-methylimidazo[1,2-a]pyridine-3-carboxylic acid

생성물 1

HCID 867135043-[({[8-(Cyclohexylmethoxy)-2-methylimidazo[1,2-a]pyridin-3-yl]carbonyl}amino)sulfonyl]propyl acetate수율 31.7%

시약·촉매·용매 3

HCID 962Water용매HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

반응 조건

온도
60 °C

실험 절차

To a suspension of 300 mg of 8-(cyclohexylmethoxy)-2-methylimidazo[1,2-a]pyridine-3-carboxylic acid in 5 ml of THF was added 253 mg of 1,1′-carbonyldiimidazole, followed by stirring at 60° C. for 1 hour. Subsequently, 283 mg of 3-(aminosulfonyl)propyl acetate and 389 μl of 1,8-diazabicyclo[5.4.0]-7-undecene were added thereto under ice-cooling, followed by stirring at room temperature overnight. To the reaction mixture were added water and ethyl acetate to carry out a layer separation operation. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and the obtained residue was purified by silica gel column chromatography. Since the reaction was not completed, to the obtained purified product were added again 57 mg of 3-(aminosulfonyl)propyl acetate, 60 mg of N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride, 38 mg of 4-(dimethylamino)pyridine, and 2 ml of DMF, followed by stirring at room temperature overnight. To the reaction mixture were added a saturated aqueous ammonium chloride solution and chloroform to carry out a layer separation operation. The organic layer was dried over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and the obtained residue was purified by silica gel column chromatography. To the obtained product were added ethyl acetate and ethanol, followed by stirring. The resulting solid was collected by filtration and dried to obtain 149 mg of 3-[({[8-(cyclohexylmethoxy)-2-methylimidazo[1,2-a]pyridin-3-yl]carbonyl}amino)sulfonyl]propyl acetate.

후처리

  1. temperatureunder ice-cooling
  2. stirringby stirring at room temperature overnight
  3. customa layer separation operation
  4. washThe organic layer was washed with saturated brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customthe solvent was evaporated under reduced pressure
  7. customthe obtained residue was purified by silica gel column chromatography
  8. custompurified product
  9. additionwere added again 57 mg of 3-(aminosulfonyl)propyl acetate, 60 mg of N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride, 38 mg of 4-(dimethylamino)pyridine, and 2 ml of DMF
  10. stirringby stirring at room temperature overnight
  11. additionTo the reaction mixture were added a saturated aqueous ammonium chloride solution and chloroform
  12. customa layer separation operation
  13. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  14. customthe solvent was evaporated under reduced pressure
  15. customthe obtained residue was purified by silica gel column chromatography
  16. additionTo the obtained product were added ethyl acetate and ethanol
  17. stirringby stirring
  18. filtrationThe resulting solid was collected by filtration
  19. customdried

출처 및 근거

ORD 기록
ord-183c6fea384d46bea28d86f3900b5540
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09447090B2

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