Morpholine → HCID 73053700, compound

HRID 870458Notes

Reaction equation

HRID 870458 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])=[CH:11][C:10]=2[Cl:32])[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:10]1[CH:11]=[C:12]([NH:15][C:16]([C:18]2[C:19](=[O:31])[N:20]([C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=3)[N:21]([CH3:24])[C:22]=2[CH3:23])=[O:17])[CH:13]=[CH:14][C:9]=1[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 73053630HCID 73053630, compound

Product 1

HCID 73053700HCID 73053700, compoundYield 25.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of N-(4-((2-aminopyridin-4-yl)oxy)-3-chlorophenyl)-1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide (135 mg, 0.3 mmol) in THF (3 mL) was added Et3N (0.080 mL, 0.6 mmol), followed by adding phenyl carbonochloridate (0.075 mL, 0.6 mmol) dropwise. The reaction mixture was stirred at rt for 2 hours, then morpholine (0.250 mL, 3.0 mmol) was added. The reaction mixture was stirred at rt for 22 hours, quenched with saturated NH4Cl aqueous (20 mL) and CH2Cl2 (20 mL). The resulted mixture was stirred at rt for 10 minutes, and extracted with CH2Cl2 (20 mL×3). The combined organic phases were washed with brine (20 mL×3), dried over anhydrous Na2SO4, and concentrated in vacuo. The residue was purified by a silica gel column chromatography (EtOAc/PE (v/v)=6/1) to give the title compound as a beige solid (43 mg, 25.4%).

Workup

  1. stirringThe reaction mixture was stirred at rt for 22 hours
  2. customquenched with saturated NH4Cl aqueous (20 mL) and CH2Cl2 (20 mL)
  3. stirringThe resulted mixture was stirred at rt for 10 minutes
  4. extractionextracted with CH2Cl2 (20 mL×3)
  5. washThe combined organic phases were washed with brine (20 mL×3)
  6. dry with materialdried over anhydrous Na2SO4
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by a silica gel column chromatography (EtOAc/PE (v/v)=6/1)

Sources & evidence

ORD record
ord-3b6b1387b57047228dd77935ddb8f94e
Source dataset
uspto-grants-2015_03
Patent number
US08969388B1

Reaction notes

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