N-Hydroxyacetamidine → N-(1-{[2-Chloro-5-(3-methyl-1,2,4-oxadiazol-5-yl)phenyl]methyl}-1H-pyrazol-3-yl)-2,6-difluorobenzamide

HRID 1946385Notes

Reaction equation

[C:1](=[N:4][OH:5])([NH2:3])[CH3:2].[O-]CC.[Na+].[Cl:10][C:11]1[CH:20]=[CH:19][C:14]([C:15](OC)=O)=[CH:13][C:12]=1[CH2:21][N:22]1[CH:26]=[CH:25][C:24]([NH:27][C:28]([C:30]2[C:35]([F:36])=[CH:34][CH:33]=[CH:32][C:31]=2[F:37])=[O:29])=[N:23]1>C(O)C>[Cl:10][C:11]1[CH:20]=[CH:19][C:14]([C:15]2[O:5][N:4]=[C:1]([CH3:2])[N:3]=2)=[CH:13][C:12]=1[CH2:21][N:22]1[CH:26]=[CH:25][C:24]([NH:27][C:28](=[O:29])[C:30]2[C:31]([F:37])=[CH:32][CH:33]=[CH:34][C:35]=2[F:36])=[N:23]1

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of acetamide oxime (89 mg, 1.20 mmol, GFS chemicals) in ethanol (2 ml) was added 4A activated molecular sieves (418 mg) (pre-dried in the oven overnight) and then 21% sodium ethoxide in ethanol (0.2 ml, 0.536 mmol, Alfa Aesar). To the reaction mixture was added methyl 4-chloro-3-[(3-{[(2,6-difluorophenyl)carbonyl]amino}-1H-pyrazol-1-yl)methyl]benzoate (for a preparation see Intermediate 23)(105 mg, 0.259 mmol). The reaction was heated to reflux (100° C.) and stirred for 3 h under nitrogen. The reaction mixture was evaporated in vacuo and the residue dissolved in methanol (0.5 ml) and filtered through a hydrophobic frit. The residue was dissolved with DMSO (0.5 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 gum (6.1 mg);

Workup

temperatureThe reaction was heated
customThe reaction mixture was evaporated in vacuo
dissolutionthe residue dissolved in methanol (0.5 ml)
filtrationfiltered through a hydrophobic frit
dissolutionThe residue was dissolved with DMSO (0.5 ml)
customthe sample was purified by MDAP on Sunfire C18 column
customThe solvent was evaporated in vacuo

Sources & evidence

ORD record: ord-d0f332b905cd402c8c7614d7c25838a7
Source dataset: uspto-grants-2013_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08399436B2

Reaction notes

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