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

HRID 2277386Notes

Reaction equation

HRID 2277386 reaction equation
[NH2:1][C:2]1[CH:24]=[CH:23][C:5]([O:6][C:7]2[C:16]3[C:11](=[CH:12][C:13]([O:17][CH2:18][C:19]([CH3:22])([OH:21])[CH3:20])=[CH:14][CH:15]=3)[N:10]=[CH:9][CH:8]=2)=[CH:4][CH:3]=1.[CH3:25][N:26]1[C:30]([CH3:31])=[C:29]([C:32](O)=[O:33])[C:28](=[O:35])[N:27]1[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1.C1C=NC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C>C(Cl)Cl.CCOC(C)=O.O>[OH:21][C:19]([CH3:22])([CH3:20])[CH2:18][O:17][C:13]1[CH:12]=[C:11]2[C:16]([C:7]([O:6][C:5]3[CH:23]=[CH:24][C:2]([NH:1][C:32]([C:29]4[C:28](=[O:35])[N:27]([C:36]5[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=5)[N:26]([CH3:25])[C:30]=4[CH3:31])=[O:33])=[CH:3][CH:4]=3)=[CH:8][CH:9]=[N:10]2)=[CH:15][CH:14]=1

Participants

8

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide2×HCID 181649HOAtHCID 246564Antipyric acidHCID 681939811-((4-(4-Aminophenoxy)quinolin-7-yl)oxy)-2-methylpropan-2-ol

Product 1

HCID 60172729N-(4-((7-(2-hydroxy-2-methylpropoxy)quinolin-4-yl)oxy)phenyl)-1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamideYield 48.87%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
45 °C

Procedure

To a solution of 1-((4-(4-aminophenoxy)quinolin-7-yl)oxy)-2-methylpropan-2-ol (3.75 g, 11.6 mmol) in DCM (31 mL) was added 1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxylic acid (2.7 g, 11.8 mmol), HOAT (0.32 g, 2.32 mmol), EDCI (2.7 g, 13.9 mmol). The reaction mixture was refluxed for 3 hours, then cooled to 45° C. and continued to stir for 4 hours. Additional EDCI (0.4 eq., 0.90 g, 4.64 mmol) was added and the reaction was stirred overnight at 45° C. The mixture was cooled to room temperature and diluted with a mixture of EtOAc (30 mL) and water (30 mL). After stirring at room temperature for 2 hours, the mixture was filtered. The solid was stirred in 95% EtOH (15 mL) at −5° C. for 5 hours. The solid was collected through filtration, dried in vacuo at 50° C. overnight to give the title compound as a gray-white solid (3.04 g, 48.87%).

Workup

  1. temperatureThe reaction mixture was refluxed for 3 hours
  2. stirringthe reaction was stirred overnight at 45° C
  3. temperatureThe mixture was cooled to room temperature
  4. stirringAfter stirring at room temperature for 2 hours
  5. filtrationthe mixture was filtered
  6. stirringThe solid was stirred in 95% EtOH (15 mL) at −5° C. for 5 hours
  7. filtrationThe solid was collected through filtration
  8. customdried in vacuo at 50° C. overnight

Sources & evidence

ORD record
ord-3064b91fa9fe4d5fb0ea624200fe39d7
Source dataset
uspto-grants-2015_09
Patent number
US09133162B2

Reaction notes

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