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

HRID 870433Notes

Reaction equation

HRID 870433 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)=[CH:4][C:3]=1[Cl:18].[CH3:19][N:20]1[C:24]([CH3:25])=[C:23]([C:26](O)=[O:27])[C:22](=[O:29])[N:21]1[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.CCN=C=NCCCN(C)C.C1C=NC2N(O)N=NC=2C=1>C(Cl)Cl.O>[Cl:18][C:3]1[CH:4]=[C:5]([CH:16]=[CH:17][C:2]=1[NH:1][C:26]([C:23]1[C:22](=[O:29])[N:21]([C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=2)[N:20]([CH3:19])[C:24]=1[CH3:25])=[O:27])[O:6][C:7]1[CH:12]=[CH:11][N:10]=[C:9]([C:13]([NH2:15])=[O:14])[CH:8]=1

Participants

7

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide2×HCID 181649HOAtHCID 246564Antipyric acid2×HCID 231535844-(4-Amino-3-chlorophenoxy)picolinamide

Product 1

HCID 730532634-(3-chloro-4-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamido)phenoxy)picolinamideYield 46.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
46 °C

Procedure

To a suspension of 4-(4-amino-3-chlorophenoxy)picolinamide (191 mg, 0.72 mmol) and 1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxylic acid (168 mg, 0.72 mmol) in DCM (10 mL) was added EDCI (166 mg, 0.86 mmol) and HOAT (20 mg, 0.14 mmol). The reaction was stirred at 46° C. for 6 hours, followed by the addition of 1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxylic acid (32 mg, 0.14 mmol) and EDCI (27 mg, 0.14 mmol). The mixture was continued to stir at 46° C. for 13 hours, then cooled to rt and diluted with water (10 mL). The resulted mixture was extracted with ethyl acetate (10 mL×3), and the combined organic phases were washed with brine (10 mL), dried over anhydrous Na2SO4, and concentrated in vacuo. The residue was purified by a silica gel column chromatography (DCM/MeOH (v/v)=50/1) to give the title compound as a pale yellow solid (160 mg, 46.5%).

Workup

  1. stirringto stir at 46° C. for 13 hours
  2. temperaturecooled to rt
  3. extractionThe resulted mixture was extracted with ethyl acetate (10 mL×3)
  4. washthe combined organic phases were washed with brine (10 mL)
  5. dry with materialdried over anhydrous Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by a silica gel column chromatography (DCM/MeOH (v/v)=50/1)

Sources & evidence

ORD record
ord-2e1666898f42412a85246c77f81d385a
Source dataset
uspto-grants-2015_03
Patent number
US08969388B1

Reaction notes

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