Hydroxylamine → HCID 75628450, compound

HRID 2370998Notes

Reaction equation

[NH2:1][OH:2].[CH3:3][C:4]1[C:8]([C:9]2[N:10]([C:25]#[N:26])[C:11]3[C:16]([C:17]=2[C:18]2[CH:23]=[CH:22][C:21]([OH:24])=[CH:20][CH:19]=2)=[CH:15][CH:14]=[CH:13][CH:12]=3)=[C:7]([CH3:27])[S:6][N:5]=1>CO>[CH3:3][C:4]1[C:8]([C:9]2[N:10]([C:25](=[N:1][OH:2])[NH2:26])[C:11]3[C:16]([C:17]=2[C:18]2[CH:23]=[CH:22][C:21]([OH:24])=[CH:20][CH:19]=2)=[CH:15][CH:14]=[CH:13][CH:12]=3)=[C:7]([CH3:27])[S:6][N:5]=1

Participants

Conditions

Temperature: 130 °C

Procedure

Hydroxylamine (16.3 M solution in water, 0.33 mL, 5.21 mmol) was added to 2-(3,5-dimethylisothiazol-4-yl)-3-(4-hydroxyphenyl)-1H-indole-1-carbonitrile (18 mg, 0.05 mmol) in MeOH (2 mL) and the reaction was stirred at 130° C. for 20 min in the microwave. The mixture was purified by preparative HPLC to give E24 2-(3,5-dimethylisothiazol-4-yl)-N′-hydroxy-3-(4-hydroxyphenyl)-1H-indole-1-carboximidamide (7.0 mg, 35%); ES/MS m/z 379.11 (M+H), 377.14 (M−H); 1H NMR (acetone-d6, 500 MHz): 7.70 (dd, 1H, J=7.9, 1.0 Hz), 7.59 (dd, 1H, J=9.0, 0.9 Hz), 7.29 (m, 1H), 7.20 (m, 1H), 7.09 (m, 2H), 6.81 (m, 2H), 2.30 (s, 3H) and 2.16 (s, 3H) and E25 2-(3,5-dimethylisothiazol-4-yl)-3-(4-hydroxyphenyl)-1H-indole-1-carboxamide (5 mg, 26%), ES/MS m/z 364.11 (M+H), 362.14 (M−H); 1H NMR (acetone-d6, 500 MHz): 8.12 (d, 1H, J=8.4 Hz), 7.67 (d, 1H, J=7.9 Hz), 7.36 (m, 1H), 7.26 (m, 1H), 7.05 (m, 2H), 6.83 (m, 2H) and 2.21 (s, 6H). For each of the title compounds, identification by 1H-NMR showed that the amide oxime product was a single isomer, but did not confirm whether the (E) or (Z) oxime isomer had been obtained.

Workup

customThe mixture was purified by preparative HPLC

Sources & evidence

ORD record: ord-36c666f142ba43ffbd88e617c2432473
Source dataset: uspto-grants-2014_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08710243B2

Reaction notes

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