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 870436Notes

Reaction equation

HRID 870436 reaction equation
[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

Participants

6

Reactant 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

Product 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-carboxamideYield 38.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

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%).

Workup

  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)

Sources & evidence

ORD record
ord-6567ae3534e641998cab4dd64d676260
Source dataset
uspto-grants-2015_03
Patent number
US08969388B1

Reaction notes

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