Hydrochloric Acid → N-(5-(7-methoxyquinolin-4-yloxy)pyridin-2-yl)-1-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide

HRID 415933ノート

反応式

HRID 415933 の反応式
[CH3:1][N:2]1[CH:6]=[C:5]([C:7]([O:9]CC)=O)[C:4](=[O:12])[N:3]1[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[OH-].[Na+].Cl.[CH3:22][O:23][C:24]1[CH:33]=[C:32]2[C:27]([C:28]([O:34][C:35]3[CH:36]=[CH:37][C:38]([NH2:41])=[N:39][CH:40]=3)=[CH:29][CH:30]=[N:31]2)=[CH:26][CH:25]=1.CCN(CC)CC.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CO.O.CN(C=O)C.CCOC(C)=O.ClCCl>[CH3:22][O:23][C:24]1[CH:33]=[C:32]2[C:27]([C:28]([O:34][C:35]3[CH:36]=[CH:37][C:38]([NH:41][C:7]([C:5]4[C:4](=[O:12])[N:3]([C:13]5[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=5)[N:2]([CH3:1])[CH:6]=4)=[O:9])=[N:39][CH:40]=3)=[CH:29][CH:30]=[N:31]2)=[CH:26][CH:25]=1

参加物

12

反応物 6

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 15192740ethyl 2,3-dihydro-1-methyl-3-oxo-2-phenyl-1H-pyrazole-4-carboxylateHCID 595983945-(7-Methoxyquinolin-4-yloxy)pyridin-2-amine

生成物 1

HCID 44516532N-(5-(7-methoxyquinolin-4-yloxy)pyridin-2-yl)-1-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide収率 20.3%

試薬・触媒・溶媒 5

HCID 887Methanol溶媒HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
60 °C

実験手順

A solution of ethyl 1-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxylate (260 mg, 1056 μmol) in MeOH was treated with NaOH (1000 μl, 5000 μmol) in H2O (3 mL). The mixture was heated to 60° C. for 30 min and then cooled to room temperature. Then, the mixture was neutralized with aq. HCl (5 N, 1.1 mL) and concentrated to dryness. The residue was further dried with (azeotrope distillation with toluene, 3×5 mL). The resulting carboxylic acid was mixed with 5-(7-methoxyquinolin-4-yloxy)pyridin-2-amine (282 mg, 1054 μmol), Et3N (500 μl, 3587 μmol), and HATU (401 mg, 1054 μmol) in DMF (4 mL)-dichloromethane (5 mL) and was stirred at 60° C. for 2 h. Upon cooling to room temperature, the mixture was diluted with EtOAc containing 10% MeOH (30 mL) and washed with H2O. The organic layer was dried over Na2SO4, concentrated, and eluded on silica (1-10% 2N NH3-MeOH in CHCl3). The product was further purified on preparative HPLC to afford a white powder (100 mg, 20%).

後処理

  1. temperaturecooled to room temperature
  2. concentrationconcentrated to dryness
  3. dry with materialThe residue was further dried with (azeotrope distillation with toluene, 3×5 mL)
  4. temperatureUpon cooling to room temperature
  5. washwashed with H2O
  6. dry with materialThe organic layer was dried over Na2SO4
  7. concentrationconcentrated
  8. customThe product was further purified on preparative HPLC

出典と根拠

ORDレコード
ord-1877856ac5484f7293ece950b61d87c0
出典データセット
uspto-grants-2012_01
特許番号
US08088794B2

反応ノート

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