Hydroxylamine → 4-(2,4-dimethylthiophen-3-yl)-3-(2-fluoro-4-hydroxyphenyl)-N'-hydroxy-1-methyl-1H-pyrazole-5-carboximidamide

HRID 1410173Notes

Reaction equation

[CH3:1][C:2]1[S:3][CH:4]=[C:5]([CH3:23])[C:6]=1[C:7]1[C:8]([C:15]2[CH:20]=[CH:19][C:18]([OH:21])=[CH:17][C:16]=2[F:22])=[N:9][N:10]([CH3:14])[C:11]=1[C:12]#[N:13].[NH2:24][OH:25].CCOC(C)=O.O>CS(C)=O>[CH3:1][C:2]1[S:3][CH:4]=[C:5]([CH3:23])[C:6]=1[C:7]1[C:8]([C:15]2[CH:20]=[CH:19][C:18]([OH:21])=[CH:17][C:16]=2[F:22])=[N:9][N:10]([CH3:14])[C:11]=1[C:12](=[N:24][OH:25])[NH2:13]

Participants

Conditions

Temperature: 150 °C

Procedure

To a solution of 4-(2,4-dimethylthiophen-3-yl)-3-(2-fluoro-4-hydroxyphenyl)-1-methyl-1H-pyrazole-5-carbonitrile (7 mg, 0.02 mmol) in DMSO (0.6 mL) was added neutral hydroxylamine solution (16 M in water, 0.33 mL, 5.35 mmol) The reaction was heated at 150° C. in the microwave for 15 min. EtOAc and water were added and the phases were separated. The crude product was purified on preparative HPLC to give 4-(2,4-dimethylthiophen-3-yl)-3-(2-fluoro-4-hydroxyphenyl)-N′-hydroxy-1-methyl-1H-pyrazole-5-carboximidamide (3.62 mg, 47%). Identification of the title compound by 1H-NMR showed that the oxime product was a single isomer, but did not confirm whether the (E) or (Z) oxime isomer had been obtained. ES/MS m/z: 361.06 (M+H), 359.14 (M−H); 1H NMR (acetone-d6, 500 MHz): 7.05 (t, 1H, J=8.6 Hz), 6.77 (q, 1H, J=0.9 Hz), 6.59 (dd, 1H, J=8.6, 2.5 Hz), 6.51 (dd, 1H, J=11.7, 2.5 Hz), 4.01 (s, 3H), 2.07 (s, 3H) and 1.88 (d, 3H, J=0.9 Hz).

Workup

customthe phases were separated
customThe crude product was purified on preparative HPLC

Sources & evidence

ORD record: ord-c776cb172bf14a739a4d84a6db21db91
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08921402B2

Reaction notes

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