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

HRID 870430Notes

Reaction equation

HRID 870430 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[C:14]([F:15])=[CH:13][C:12]([NH:16][C:17]([C:19]3[C:20](=[O:32])[N:21]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)[N:22]([CH3:25])[C:23]=3[CH3:24])=[O:18])=[C:11]([F:33])[CH:10]=2)[CH:5]=[CH:4][N:3]=1.CCN(CC)CC.[C:41](Cl)(=O)[O:42]C1C=CC=CC=1.[NH:51]1[CH2:56][CH2:55][O:54][CH2:53][CH2:52]1>C1COCC1>[CH3:25][N:22]1[C:23]([CH3:24])=[C:19]([C:17]([NH:16][C:12]2[C:11]([F:33])=[CH:10][C:9]([O:8][C:6]3[CH:5]=[CH:4][N:3]=[C:2]([NH:1][C:41]([N:51]4[CH2:56][CH2:55][O:54][CH2:53][CH2:52]4)=[O:42])[CH:7]=3)=[C:14]([F:15])[CH:13]=2)=[O:18])[C:20](=[O:32])[N:21]1[C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1

Participants

6

Reactant 4

HCID 8083MorpholineHCID 8471TriethylamineHCID 15891Phenyl chloroformateHCID 73053611N-(4-((2-aminopyridin-4-yl)oxy)-2,5-difluorophenyl)-1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide

Product 1

HCID 73053698N-(4-(4-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamido)-2,5-difluorophenoxy)pyridin-2-yl)morpholine-4-carboxamideYield 22.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of N-(4-((2-aminopyridin-4-yl)oxy)-2,5-difluorophenyl)-1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide (250 mg, 0.56 mmol) and Et3N (0.25 mL, 1.68 mmol) in THF (10.0 mL) was added phenyl carbonochloridate (0.25 mL, 1.68 mmol). The mixture was stirred at rt for 2 hours, then morpholine (0.35 mL, 3.46 mmol) was added. The reaction mixture was stirred rt for 24 hours and partitioned between aq NH4Cl (40 mL) and DCM (40 mL). The organic phase was separated and the aqueous phase was extracted with DCM (40 mL×3). The combined organic phases was dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by a silica gel column chromatography (EtOAc/PE (v/v)=4/1) to give the title compound as a white solid (70 mg, 21%).

Workup

  1. stirringThe reaction mixture was stirred rt for 24 hours
  2. custompartitioned between aq NH4Cl (40 mL) and DCM (40 mL)
  3. customThe organic phase was separated
  4. extractionthe aqueous phase was extracted with DCM (40 mL×3)
  5. dry with materialThe combined organic phases was dried over anhydrous Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by a silica gel column chromatography (EtOAc/PE (v/v)=4/1)

Sources & evidence

ORD record
ord-ef362049e75f403ca3ea32cdcae8b1d7
Source dataset
uspto-grants-2015_03
Patent number
US08969388B1

Reaction notes

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