2-Chloro-6-fluorobenzoic acid → 2-Chloro-N-[1-({5-chloro-2-[(phenylmethyl)oxy]phenyl}methyl)-1H-pyrazol-3-yl]-6-fluorobenzamide

HRID 1946427Notes

Reaction equation

HRID 1946427 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([F:11])[C:3]=1[C:4]([OH:6])=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:45][C:46]1[CH:47]=[CH:48][C:49]([O:59][CH2:60][C:61]2[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=2)=[C:50]([CH2:52][N:53]2[CH:57]=[CH:56][C:55]([NH2:58])=[N:54]2)[CH:51]=1>CN(C=O)C>[Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([F:11])[C:3]=1[C:4]([NH:58][C:55]1[CH:56]=[CH:57][N:53]([CH2:52][C:50]2[CH:51]=[C:46]([Cl:45])[CH:47]=[CH:48][C:49]=2[O:59][CH2:60][C:61]2[CH:62]=[CH:63][CH:64]=[CH:65][CH:66]=2)[N:54]=1)=[O:6]

Participants

6

Reactant 4

HCID 679472-Chloro-6-fluorobenzoic acidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 578755491-({5-Chloro-2-[(phenylmethyl)oxy]phenyl}methyl)-1H-pyrazol-3-amine

Product 1

HCID 595479542-Chloro-N-[1-({5-chloro-2-[(phenylmethyl)oxy]phenyl}methyl)-1H-pyrazol-3-yl]-6-fluorobenzamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

To a solution of 2-chloro-6-fluorobenzoic acid (18 mg, 0.1 mmol, Aldrich) in DMF (0.1 ml) was added a solution of HATU (38 mg, 0.1 mmol) in DMF (0.2 ml). After 5 min, DIPEA (0.050 ml, 0.27 mmol) was added to the mixture. To the mixture was added a solution of 1-({5-chloro-2-[(phenylmethyl)oxy]phenyl}methyl)-1H-pyrazol-3-amine (for a preparation see Intermediate 55)(0.1 mmol) in DMF (0.1 ml). After shaking for 10 min, the resulting solution was allowed to stand for 16 h at ambient temperature. The solvent was removed using a genevac. The sample was dissolved in 1:1 MeOH:DMSO (0.6 ml) and purified by MDAP on a C18 column using Acetonitrile-Water with a TFA modifier (Method D). The solvent was evaporated in vacuo using the Genevac to give the title compound; LCMS (System 3) MH+=470/472, tRET=1.32 min.

Workup

  1. waitto stand for 16 h at ambient temperature
  2. customThe solvent was removed
  3. dissolutionThe sample was dissolved in 1:1 MeOH
  4. customDMSO (0.6 ml) and purified by MDAP on a C18 column
  5. customThe solvent was evaporated in vacuo

Sources & evidence

ORD record
ord-f10750b87f584d34838e4fdeb69efe8a
Source dataset
uspto-grants-2013_03
Patent number
US08399436B2

Reaction notes

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