Diisopropylethylamine → N-(1-{[4-Chloro-2-(trifluoromethyl)phenyl]methyl}-1H-pyrazol-3-yl)-3-fluoro-4-pyridinecarboxamide
Reaction equation
[F:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[C:8]([OH:10])=O.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[Cl:44][C:45]1[CH:50]=[CH:49][C:48]([CH2:51][N:52]2[CH:56]=[CH:55][C:54]([NH2:57])=[N:53]2)=[C:47]([C:58]([F:61])([F:60])[F:59])[CH:46]=1>CN(C=O)C.CO>[Cl:44][C:45]1[CH:50]=[CH:49][C:48]([CH2:51][N:52]2[CH:56]=[CH:55][C:54]([NH:57][C:8]([C:7]3[CH:6]=[CH:5][N:4]=[CH:3][C:2]=3[F:1])=[O:10])=[N:53]2)=[C:47]([C:58]([F:59])([F:61])[F:60])[CH:46]=1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Procedure
To 3-fluoro-4-pyridinecarboxylic acid (27 mg, 0.191 mmol, Aldrich) was added a solution of HATU (24 mg, 0.189 mmol, Advanced asymmetrics) in DMF (0.5 ml), DIPEA (0.076 ml, 0.435 mmol) and then a solution of 1-{[4-chloro-2-(trifluoromethyl)phenyl]methyl}-1H-pyrazol-3-amine (for a preparation see Intermediate 37)(40 mg, 0.145 mmol) in DMF (0.5 ml). The resulting yellow solution was stirred at ambient temperature overnight. Further amounts of HATU (72 mg, 0.189 mmol), 3-fluoro-4-pyridinecarboxylic acid (27 mg, 0.191 mmol) and DIPEA (0.076 ml, 0.435 mmol) were added. The reaction mixture was stirred at ambient temperature for a further 2 h. The reaction mixture was diluted with methanol and purified by MDAP on Sunfire C18 column (Method B) using Acetonitrile-Water with a Formic acid modifier. The solvent was evaporated in vacuo to give the title compound as a white solid (49 mg); LCMS: (System 4) MH+=399 tRET=2.82 min.
Workup
- stirringThe reaction mixture was stirred at ambient temperature for a further 2 h
- custompurified by MDAP on Sunfire C18 column (Method B)
- customThe solvent was evaporated in vacuo
Sources & evidence
- ORD record
- ord-13c285ef697d44fa93b11569cdcccd13
- Source dataset
- uspto-grants-2013_03
- Patent number
- US08399436B2
Reaction notes
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