1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 3-((4-((6-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamido)pyridin-3-yl)oxy)pyridin-2-yl)carbamoyl)cyclobutyl acetate

HRID 520709Notes

Reaction equation

HRID 520709 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:10]=[CH:11][C:12]([NH:15][C:16]([C:18]3[C:19](=[O:31])[N:20]([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)[N:21]([CH3:24])[C:22]=3[CH3:23])=[O:17])=[N:13][CH:14]=2)[CH:5]=[CH:4][N:3]=1.C1C=NC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.CCN(C(C)C)C(C)C.[C:62]([O:65][CH:66]1[CH2:69][CH:68]([C:70](O)=[O:71])[CH2:67]1)(=[O:64])[CH3:63]>CN(C=O)C.O>[C:62]([O:65][CH:66]1[CH2:69][CH:68]([C:70](=[O:71])[NH:1][C:2]2[CH:7]=[C:6]([O:8][C:9]3[CH:14]=[N:13][C:12]([NH:15][C:16]([C:18]4[C:19](=[O:31])[N:20]([C:25]5[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=5)[N:21]([CH3:24])[C:22]=4[CH3:23])=[O:17])=[CH:11][CH:10]=3)[CH:5]=[CH:4][N:3]=2)[CH2:67]1)(=[O:64])[CH3:63]

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 73053627N-(5-((2-aminopyridin-4-yl)oxy)pyridin-2-yl)-1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamideHCID 898403503-Acetoxycyclobutanecarboxylic acid

Product 1

HCID 900336043-((4-((6-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamido)pyridin-3-yl)oxy)pyridin-2-yl)carbamoyl)cyclobutyl acetateYield 30%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
120 °C

Procedure

To a solution of N-(5-((2-aminopyridin-4-yl)oxy)pyridin-2-yl)-1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide (50 mg, 0.12 mmol), HOAT (19 mg, 0.24 mmol), EDCI (28 mg, 0.14 mmol) and DIPEA (0.1 mL, 0.6 mmol) in DMF (5 mL) was added a solution of 3-acetoxycyclobutanecarboxylic acid in DMF (5 mL) at 0° C. The reaction was heated at 120° C. for 5 hours, then cooled to rt, diluted with water (50 mL) and extracted with EtOAc (30 mL×3). The combined organic phases were washed with brine (10 mL), dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The resulted residue was purified by a silica gel column chromatography (DCM/EtOAc (v/v)=1/2) to give the title compound as a white solid (20 mg, 30%).

Workup

  1. temperaturecooled to rt
  2. extractionextracted with EtOAc (30 mL×3)
  3. washThe combined organic phases were washed with brine (10 mL)
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe resulted residue was purified by a silica gel column chromatography (DCM/EtOAc (v/v)=1/2)

Sources & evidence

ORD record
ord-3d27d65c36f240aca0a30675e300fab4
Source dataset
uspto-grants-2016_05
Patent number
US09326975B2

Reaction notes

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