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 2095947ノート

反応式

HRID 2095947 の反応式
[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

参加物

11

反応物 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

生成物 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-carboxamide収率 34%

試薬・触媒・溶媒 5

HCID 702Ethanol溶媒HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒2 回HCID 25517Ammonium Chloride溶媒2 回

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-8569d5582ea54fe8b700fa0e1c2c2301
出典データセット
uspto-grants-2013_05
特許番号
US08445509B2

反応ノート

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