N-[1-({5-[(2-acetylhydrazino)carbonyl]-2-chlorophenyl}methyl)-1H-pyrazol-3-yl]-2,6-difluorobenzamide → N-(1-{[2-chloro-5-(5-methyl-1,3,4-oxadiazol-2-yl)phenyl]methyl}-1H-pyrazol-3-yl)-2,6-difluorobenzamide

HRID 1946428Notes

Reaction equation

HRID 1946428 reaction equation
[C:1]([NH:4][NH:5][C:6]([C:8]1[CH:9]=[CH:10][C:11]([Cl:31])=[C:12]([CH2:14][N:15]2[CH:19]=[CH:18][C:17]([NH:20][C:21](=[O:30])[C:22]3[C:27]([F:28])=[CH:26][CH:25]=[CH:24][C:23]=3[F:29])=[N:16]2)[CH:13]=1)=O)(=[O:3])[CH3:2]>C1COCC1>[Cl:31][C:11]1[CH:10]=[CH:9][C:8]([C:6]2[O:3][C:1]([CH3:2])=[N:4][N:5]=2)=[CH:13][C:12]=1[CH2:14][N:15]1[CH:19]=[CH:18][C:17]([NH:20][C:21](=[O:30])[C:22]2[C:27]([F:28])=[CH:26][CH:25]=[CH:24][C:23]=2[F:29])=[N:16]1

Participants

3

Reactant 1

HCID 59547995N-[1-({5-[(2-acetylhydrazino)carbonyl]-2-chlorophenyl}methyl)-1H-pyrazol-3-yl]-2,6-difluorobenzamide

Product 1

HCID 59547952N-(1-{[2-chloro-5-(5-methyl-1,3,4-oxadiazol-2-yl)phenyl]methyl}-1H-pyrazol-3-yl)-2,6-difluorobenzamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of N-[1-({5-[(2-acetylhydrazino)carbonyl]-2-chlorophenyl}methyl)-1H-pyrazol-3-yl]-2,6-difluorobenzamide (for a preparation see Intermediate 51)(130 mg, 0.290 mmol) in THF (4 ml) was added 4A molecular sieves (513 mg) (pre-dried in an oven) and then (methoxycarbonylsulfamoyl)triethylammonium hydroxide, inner salt (21 mg, 0.088 mmol, Fluka). The reaction vessel was sealed and heated in a Biotage Initiator microwave to 150° C. for 25 min. The solvent was evaporated in vacuo, the residue was dissolved in methanol (1 ml) and then filtered through a hydrophobic frit. The filtrate was dissolved in DMSO (1 ml) and the sample was purified by MDAP on Sunfire C18 column using Acetonitrile-Water with a Formic acid modifier (Method B). The solvent was evaporated in vacuo to give the title compound as a white solid (13 mg); LCMS (System 3) MH+=430/432, tRET=2.54 min.

Workup

  1. additionwas added
  2. dry with material4A molecular sieves (513 mg) (pre-dried in an oven)
  3. customThe reaction vessel was sealed
  4. customThe solvent was evaporated in vacuo
  5. dissolutionthe residue was dissolved in methanol (1 ml)
  6. filtrationfiltered through a hydrophobic frit
  7. dissolutionThe filtrate was dissolved in DMSO (1 ml)
  8. customthe sample was purified by MDAP on Sunfire C18 column
  9. customThe solvent was evaporated in vacuo

Sources & evidence

ORD record
ord-491f506fcd654ac795d2a7d74b4d28ba
Source dataset
uspto-grants-2013_03
Patent number
US08399436B2

Reaction notes

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