Diisopropylethylamine → N-[4-({2-[(cyclopropylcarbonyl)amino]-3-fluoroimidazo[1,2-a]pyridin-6-yl}oxy)-3-fluorophenyl]-1-(4-fluorophenyl)-6-methyl-2-oxo-1,2-dihydropyridine-3-carboxamide

HRID 2095947노트

반응식

HRID 2095947 반응식
[F:1][C:2]1[N:6]2[CH:7]=[C:8]([O:11][C:12]3[CH:17]=[CH:16][C:15]([N+:18]([O-])=O)=[CH:14][C:13]=3[F:21])[CH:9]=[CH:10][C:5]2=[N:4][C:3]=1[NH:22][C:23]([CH:25]1[CH2:27][CH2:26]1)=[O:24].[F:28][C:29]1[CH:34]=[CH:33][C:32]([N:35]2[C:40]([CH3:41])=[CH:39][CH:38]=[C:37]([C:42](O)=[O:43])[C:36]2=[O:45])=[CH:31][CH:30]=1.C(N(CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(=O)([O-])O.[Na+]>C(O)C.O.C(OCC)(=O)C.[Cl-].[NH4+].CN(C)C=O>[CH:25]1([C:23]([NH:22][C:3]2[N:4]=[C:5]3[CH:10]=[CH:9][C:8]([O:11][C:12]4[CH:17]=[CH:16][C:15]([NH:18][C:42]([C:37]5[C:36](=[O:45])[N:35]([C:32]6[CH:31]=[CH:30][C:29]([F:28])=[CH:34][CH:33]=6)[C:40]([CH3:41])=[CH:39][CH:38]=5)=[O:43])=[CH:14][C:13]=4[F:21])=[CH:7][N:6]3[C:2]=2[F:1])=[O:24])[CH2:27][CH2:26]1

참가 물질

11

반응물 5

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 210815291-(4-Fluorophenyl)-6-methyl-2-oxo-1,2-dihydropyridine-3-carboxylic acidHCID 58158450N-[3-fluoro-6-(2-fluoro-4-nitrophenoxy)imidazo[1,2-a]pyridin-2-yl]cyclopropanecarboxamide

생성물 1

HCID 58158539N-[4-({2-[(cyclopropylcarbonyl)amino]-3-fluoroimidazo[1,2-a]pyridin-6-yl}oxy)-3-fluorophenyl]-1-(4-fluorophenyl)-6-methyl-2-oxo-1,2-dihydropyridine-3-carboxamide수율 34%

시약·촉매·용매 5

HCID 702Ethanol용매HCID 962Water용매HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매2회HCID 25517Ammonium Chloride용매2회

실험 절차

A mixed solution of N-[3-fluoro-6-(2-fluoro-4-nitrophenoxy)imidazo[1,2-a]pyridin-2-yl]cyclopropanecarboxamide (15.2 mg, 0.041 mmol), reduced iron (12.1 mg, 0.205 mmol) and ammonium chloride (21.9 mg, 0.41 mmol) in ethanol (1 mL) and water (0.2 mL) was stirred at 90° C. for 5 hr. The reaction mixture was diluted with ethyl acetate and saturated aqueous ammonium chloride solution and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and filtered, and the solvent was evaporated under reduced pressure. To a solution of the obtained residue and 1-(4-fluorophenyl)-6-methyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid (12.2 mg, 0.0492 mmol) in N,N-dimethylformamide (1 mL) were added N,N-diisopropylethylamine (14 μL, 0.082 mmol) and HATU (18.7 mg, 0.0492 mmol), and the mixture was stirred at room temperature for 17 hr. Ethyl acetate and saturated aqueous sodium hydrogen carbonate solution were added to the reaction mixture, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and filtered, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane=2/1→ethyl acetate alone) to give a white solid. The obtained solid was washed with ethyl acetate and collected by filtration to give the title compound (8 mg, 34%) as a white solid.

후처리

  1. extractionextracted twice with ethyl acetate
  2. washThe organic layer was washed with saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. customthe solvent was evaporated under reduced pressure
  6. extractionthe mixture was extracted 3 times with ethyl acetate
  7. washThe organic layer was washed with saturated brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. filtrationfiltered
  10. customthe solvent was evaporated under reduced pressure
  11. customThe obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane=2/1→ethyl acetate alone)
  12. customto give a white solid
  13. washThe obtained solid was washed with ethyl acetate
  14. filtrationcollected by filtration

출처 및 근거

ORD 기록
ord-8569d5582ea54fe8b700fa0e1c2c2301
출처 데이터셋
uspto-grants-2013_05
특허 번호
US08445509B2

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