Morpholine → N-(4-(3-chloro-4-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamido)phenoxy)pyridin-2-yl)morpholine-4-carboxamide

HRID 870436ノート

反応式

HRID 870436 の反応式
[NH2:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16]([C:18]3[C:19](=[O:31])[N:20]([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)[N:21]([CH3:24])[C:22]=3[CH3:23])=[O:17])=[C:11]([Cl:32])[CH:10]=2)[CH:5]=[CH:4][N:3]=1.CCN(CC)CC.[C:40](Cl)(=O)[O:41]C1C=CC=CC=1.[NH:50]1[CH2:55][CH2:54][O:53][CH2:52][CH2:51]1>C1COCC1>[Cl:32][C:11]1[CH:10]=[C:9]([CH:14]=[CH:13][C:12]=1[NH:15][C:16]([C:18]1[C:19](=[O:31])[N:20]([C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)[N:21]([CH3:24])[C:22]=1[CH3:23])=[O:17])[O:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([NH:1][C:40]([N:50]2[CH2:55][CH2:54][O:53][CH2:52][CH2:51]2)=[O:41])[CH:7]=1

参加物

6

反応物 4

HCID 8083MorpholineHCID 8471TriethylamineHCID 15891Phenyl chloroformateHCID 73053612N-(4-((2-aminopyridin-4-yl)oxy)-2-chlorophenyl)-1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide

生成物 1

HCID 73053686N-(4-(3-chloro-4-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamido)phenoxy)pyridin-2-yl)morpholine-4-carboxamide収率 38.1%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

To a suspension of N-(4-((2-aminopyridin-4-yl)oxy)-2-chlorophenyl)-1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide (125 mg, 0.28 mmol) and Et3N (0.12 mL, 0.84 mmol) in THF (4.0 mL) was added phenyl carbonochloridate (0.10 mL, 0.84 mmol). The mixture was stirred at rt for 2 hours, then morpholine (0.15 mL, 1.68 mmol) was added. The resulted mixture was stirred rt for 22 hours, then partitioned between aqueous NH4Cl solution (20 mL) and DCM (20 mL). The organic phase was separated and the aqueous phase was extracted with DCM (20 mL×3). The combined organic phases were dried over anhydrous Na2SO4, and concentrated in vacuo. The residue was purified by a silica gel column chromatography (EtOAc/PE (v/v)=20/1), followed by washing with methanol (4 mL) to give the title compound as a beige solid (60 mg, 38%).

後処理

  1. stirringThe resulted mixture was stirred rt for 22 hours
  2. custompartitioned between aqueous NH4Cl solution (20 mL) and DCM (20 mL)
  3. customThe organic phase was separated
  4. extractionthe aqueous phase was extracted with DCM (20 mL×3)
  5. dry with materialThe combined organic phases were dried over anhydrous Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by a silica gel column chromatography (EtOAc/PE (v/v)=20/1)
  8. washby washing with methanol (4 mL)

出典と根拠

ORDレコード
ord-6567ae3534e641998cab4dd64d676260
出典データセット
uspto-grants-2015_03
特許番号
US08969388B1

反応ノート

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