1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → N-(3-fluoro-4-((7-hydroxyquinolin-4-yl)oxy)phenyl)-1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide

HRID 2277374Notes

Reaction equation

HRID 2277374 reaction equation
[NH2:1][C:2]1[CH:19]=[CH:18][C:5]([O:6][C:7]2[C:16]3[C:11](=[CH:12][C:13]([OH:17])=[CH:14][CH:15]=3)[N:10]=[CH:9][CH:8]=2)=[C:4]([F:20])[CH:3]=1.[CH3:21][N:22]1[C:26]([CH3:27])=[C:25]([C:28](O)=[O:29])[C:24](=[O:31])[N:23]1[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1.C1C=NC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C>CN(C=O)C.C1(C)C=CC=CC=1.O>[F:20][C:4]1[CH:3]=[C:2]([NH:1][C:28]([C:25]2[C:24](=[O:31])[N:23]([C:32]3[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=3)[N:22]([CH3:21])[C:26]=2[CH3:27])=[O:29])[CH:19]=[CH:18][C:5]=1[O:6][C:7]1[C:16]2[C:11](=[CH:12][C:13]([OH:17])=[CH:14][CH:15]=2)[N:10]=[CH:9][CH:8]=1

Participants

8

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 181649HOAtHCID 246564Antipyric acidHCID 1363502984-(4-Amino-2-fluorophenoxy)quinolin-7-ol

Product 1

HCID 136347997N-(3-fluoro-4-((7-hydroxyquinolin-4-yl)oxy)phenyl)-1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamideYield 65.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
45 °C

Procedure

To a solution of 4-(4-amino-2-fluorophenoxy)quinolin-7-ol (10 g, 37.0 mmol), 1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxylic acid (10 g, 44.4 mmol), HOAT (0.5 g, 3.7 mmol) in DMF (50 mL) and toluene (30 mL) was added EDCI (8.5 g, 44.4 mmol). The reaction was stirred at 45° C. overnight, then diluted with water (100 mL) and continued to stir at room temperature for 2 hours. The solid was collected through filtration, washed with a mixture of 95% EtOH (50 mL) and DCM (25 mL), and then treated with 3 M hydrochloric acid (10.5 mL). The resulted solid was collected and was recrystallized in a mixture of 95% EtOH and H2O (90 mL, EtOH/H2O=5:1, v/v) to give the title compound as a white solid (11.7 g, 60.8%).

Workup

  1. stirringto stir at room temperature for 2 hours
  2. filtrationThe solid was collected through filtration
  3. washwashed with a mixture of 95% EtOH (50 mL) and DCM (25 mL)
  4. additiontreated with 3 M hydrochloric acid (10.5 mL)
  5. customThe resulted solid was collected
  6. customwas recrystallized in a mixture of 95% EtOH and H2O (90 mL, EtOH/H2O=5:1

Sources & evidence

ORD record
ord-06e6aec3e989469f9ec77b1c678cdf3a
Source dataset
uspto-grants-2015_09
Patent number
US09133162B2

Reaction notes

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