1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 4-(4-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamido)-2,3-difluorophenoxy)picolinamide

HRID 520669Notes

Reaction equation

HRID 520669 reaction equation
[NH2:1][C:2]1[CH:17]=[CH:16][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]([C:13]([NH2:15])=[O:14])[CH:8]=2)=[C:4]([F:18])[C:3]=1[F:19].[CH3:20][N:21]1[C:25]([CH3:26])=[C:24]([C:27](O)=[O:28])[C:23](=[O:30])[N:22]1[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.CCN=C=NCCCN(C)C.C1C=NC2N(O)N=NC=2C=1>C(Cl)Cl>[CH3:20][N:21]1[C:25]([CH3:26])=[C:24]([C:27]([NH:1][C:2]2[CH:17]=[CH:16][C:5]([O:6][C:7]3[CH:12]=[CH:11][N:10]=[C:9]([C:13]([NH2:15])=[O:14])[CH:8]=3)=[C:4]([F:18])[C:3]=2[F:19])=[O:28])[C:23](=[O:30])[N:22]1[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1

Participants

6

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 181649HOAtHCID 246564Antipyric acid2×HCID 574708784-(4-Amino-2,3-difluorophenoxy)pyridine-2-carboxamide

Product 1

HCID 730532644-(4-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamido)-2,3-difluorophenoxy)picolinamideYield 33.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
45 °C

Procedure

To a suspension of 4-(4-amino-2,3-difluorophenoxy)picolinamide (180 mg, 0.68 mmol) and 1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxylic acid (161 mg, 0.69 mmol) in DCM (4 mL) was added EDCI (157 mg, 0.82 mmol) and HOAT (19 mg, 0.14 mmol). The mixture was stirred at 45° C. for 12 hours, then more 1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxylic acid (87 mg, 0.37 mmol) was added and the reaction was further stirred at 45° C. for 5 hours. The mixture was cooled to rt, quenched with 5 mL of water, and extracted with EtOAc (10 mL×3). The combined organic phases were washed with brine (10 mL×3), dried over Na2SO4, and concentrated in vacuo. The residue was purified by a silica gel column chromatography (EtOAc 100%) to give the title compound as an orange solid (108 mg, 33.2%).

Workup

  1. stirringthe reaction was further stirred at 45° C. for 5 hours
  2. temperatureThe mixture was cooled to rt
  3. customquenched with 5 mL of water
  4. extractionextracted with EtOAc (10 mL×3)
  5. washThe combined organic phases were washed with brine (10 mL×3)
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by a silica gel column chromatography (EtOAc 100%)

Sources & evidence

ORD record
ord-5d770289d1b74e058ca3e976352bdc20
Source dataset
uspto-grants-2016_05
Patent number
US09326975B2

Reaction notes

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