Diisopropylethylamine → 5-{[2,4-dichloro-5-(3-fluoropyridin-2-yl)benzoyl]amino}-N-[1-(methylcarbamoyl)cyclopropyl]-1-phenyl-1H-pyrazole-3-carboxamide

HRID 522123Notes

Reaction equation

HRID 522123 reaction equation
[Cl:1][C:2]1[CH:24]=[C:23]([Cl:25])[C:22]([C:26]2[C:31]([F:32])=[CH:30][CH:29]=[CH:28][N:27]=2)=[CH:21][C:3]=1[C:4]([NH:6][C:7]1[N:11]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[N:10]=[C:9]([C:18](O)=[O:19])[CH:8]=1)=[O:5].C(N(CC)C(C)C)(C)C.[B-](F)(F)(F)F.CN(C(ON1C(=O)C=CC=C1)=[N+](C)C)C.[NH2:62][C:63]1([C:66]([NH:68][CH3:69])=[O:67])[CH2:65][CH2:64]1>CN(C=O)C.O>[Cl:1][C:2]1[CH:24]=[C:23]([Cl:25])[C:22]([C:26]2[C:31]([F:32])=[CH:30][CH:29]=[CH:28][N:27]=2)=[CH:21][C:3]=1[C:4]([NH:6][C:7]1[N:11]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[N:10]=[C:9]([C:18]([NH:62][C:63]2([C:66](=[O:67])[NH:68][CH3:69])[CH2:65][CH2:64]2)=[O:19])[CH:8]=1)=[O:5]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733204O-(2-Oxo-1(2H)-pyridyl)-N,N,N',N'-tetramethyluronium TetrafluoroborateHCID 587371021-amino-N-methylcyclopropane-1-carboxamideHCID 1184970555-(2,4-dichloro-5-(3-fluoropyridin-2-yl)benzamido)-1-phenyl-1H-pyrazole-3-carboxylic acid

Product 1

HCID 1184970575-{[2,4-dichloro-5-(3-fluoropyridin-2-yl)benzoyl]amino}-N-[1-(methylcarbamoyl)cyclopropyl]-1-phenyl-1H-pyrazole-3-carboxamideYield 79.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 5-(2,4-dichloro-5-(3-fluoropyridin-2-yl)benzamido)-1-phenyl-1H-pyrazole-3-carboxylic acid (Example 107, 961 mg, 2.04 mmol) in DMF (20 mL), were added N,N-diisopropylethylamine (0.8 mL, 5.5 mmol) and TPTU (848 mg, 2.85 mmol) and the mixture stirred at room temperature for 5 minutes. 1-Amino-N-methylcyclopropanecarboxamide (PCT Int. Appl., 2008051547) (300 mg, 2.65 mmol) was then added and the mixture stirred for 30 minutes. The reaction mixture was diluted with water (100 mL) and extracted with EtOAc (3×20 mL). The combined organic layers were washed with saturated aqueous brine solution, dried (magnesium sulphate) and concentrated in vacuo. The residue was purified by column chromatography over silica gel, eluting with EtOAc to afford the title compound as a white solid (916 mg, 79%). Crystallisation by vapour diffusion using methanol as the solvent and acetonitrile as the anti-solvent also afforded the title compound as crystalline colourless needles.

Workup

  1. stirringthe mixture stirred for 30 minutes
  2. extractionextracted with EtOAc (3×20 mL)
  3. washThe combined organic layers were washed with saturated aqueous brine solution
  4. dry with materialdried (magnesium sulphate)
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by column chromatography over silica gel
  7. washeluting with EtOAc

Sources & evidence

ORD record
ord-80e2b61469f64d2daaca930e2f78151e
Source dataset
uspto-grants-2016_05
Patent number
US09328096B2

Reaction notes

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