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

HRID 2277392
Notes
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Reaction equation

HRID 2277392 reaction equation
[NH2:1][C:2]1[CH:23]=[CH:22][C:5]([O:6][C:7]2[C:16]3[C:11](=[CH:12][C:13]([O:17][CH2:18][C@H:19]([OH:21])[CH3:20])=[CH:14][CH:15]=3)[N:10]=[CH:9][CH:8]=2)=[CH:4][CH:3]=1.[CH3:24][N:25]1[C:29]([CH3:30])=[C:28]([C:31](O)=[O:32])[C:27](=[O:34])[N:26]1[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.C1C=NC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C>C(Cl)Cl.O>[OH:21][C@H:19]([CH3:20])[CH2:18][O:17][C:13]1[CH:12]=[C:11]2[C:16]([C:7]([O:6][C:5]3[CH:4]=[CH:3][C:2]([NH:1][C:31]([C:28]4[C:27](=[O:34])[N:26]([C:35]5[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=5)[N:25]([CH3:24])[C:29]=4[CH3:30])=[O:32])=[CH:23][CH:22]=3)=[CH:8][CH:9]=[N:10]2)=[CH:15][CH:14]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 181649HOAtHCID 246564Antipyric acidHCID 68193946(R)-1-((4-(4-aminophenoxy)quinolin-7-yl)oxy)propan-2-ol

Product 1

HCID 60172730(R)-N-(4-((7-(2-hydroxypropoxy)quinolin-4-yl)oxy)phenyl)-1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamideYield 14.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
43 °C

Procedure

To a solution of (R)-1-((4-(4-aminophenoxy)quinolin-7-yl)oxy)propan-2-ol (2.5 g, 11.9 mmol), 1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carb oxylic acid (2.0 g, 8.6 mmol) and HOAT (0.2 g, 1.6 mmol) in DCM (35 mL) was added EDCI (1.9 g, 9.7 mmol). The reaction mixture was stirred at 43° C. for 12 hours, then cooled to room temperature and diluted with a mixture of DCM and H2O (50 mL/50 mL). The organic phase was separated, dried over Na2SO4 and concentrated in vacuo. The residue was purified by a column chromatography on silica gel (EtOAc) to afford the title compound as a yellow solid (0.6 g, 14.3%).

Workup

  1. temperaturecooled to room temperature
  2. customThe organic phase was separated
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by a column chromatography on silica gel (EtOAc)

Sources & evidence

ORD record
ord-dbe2299a314547f489025eb3e15eb38b
Source dataset
uspto-grants-2015_09
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09133162B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes