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

HRID 520666Notes

Reaction equation

HRID 520666 reaction equation
[NH2:1][C:2]1[CH:18]=[CH:17][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]([C:13]([NH2:15])=[O:14])[C:8]=2[Cl:16])=[C:4]([F:19])[CH:3]=1.[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>[Cl:16][C:8]1[C:9]([C:13]([NH2:15])=[O:14])=[N:10][CH:11]=[CH:12][C:7]=1[O:6][C:5]1[CH:17]=[CH:18][C:2]([NH:1][C:27]([C:24]2[C:23](=[O:30])[N:22]([C:31]3[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=3)[N:21]([CH3:20])[C:25]=2[CH3:26])=[O:28])=[CH:3][C:4]=1[F:19]

Participants

6

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 181649HOAtHCID 246564Antipyric acidHCID 252319754-(4-Amino-2-fluorophenoxy)-3-chloropicolinamide

Product 1

HCID 730531193-chloro-4-(4-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamido)-2-fluorophenoxy)picolinamideYield 93.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
45 °C

Procedure

To a suspension of 4-(4-amino-2-fluorophenoxy)-3-chloropicolinamide (306 mg, 1.40 mmol) and 1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxylic acid (390 mg, 1.68 mmol) in DCM (6 mL) was added EDCI (322 mg, 1.68 mmol) and HOAT (38 mg, 0.28 mmol). The mixture was stirred at 45° C. for 14.5 hours, then cooled to rt and quenched with 5 mL of water. The mixture was extracted with EtOAc (10 mL×3) and 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 (PE/EtOAc (v/v)=1/4) to give the title compound as a pale yellow solid (647 mg, 93.2%).

Workup

  1. temperaturecooled to rt
  2. customquenched with 5 mL of water
  3. extractionThe mixture was extracted with EtOAc (10 mL×3)
  4. washthe combined organic phases were washed with brine (10 mL×3)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by a silica gel column chromatography (PE/EtOAc (v/v)=1/4)

Sources & evidence

ORD record
ord-1ea70aecf88844cba7103634b9f600c5
Source dataset
uspto-grants-2016_05
Patent number
US09326975B2

Reaction notes

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