Hydroxylamine → HCID 86669036, compound

HRID 2370994Notes

Reaction equation

[NH2:1][OH:2].[Cl:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[N:9]([C:13]#[N:14])[C:8]([C:15]1[C:19]([CH3:20])=[CH:18][S:17][C:16]=1[CH3:21])=[C:7]2[C:22]1[CH:27]=[CH:26][C:25]([OH:28])=[CH:24][CH:23]=1>C(Cl)Cl.[Cl-].[Na+].O>[Cl:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[N:9]([C:13](=[N:1][OH:2])[NH2:14])[C:8]([C:15]1[C:19]([CH3:20])=[CH:18][S:17][C:16]=1[CH3:21])=[C:7]2[C:22]1[CH:27]=[CH:26][C:25]([OH:28])=[CH:24][CH:23]=1

Participants

Conditions

Temperature: 0 °C

Procedure

Hydroxylamine (16.3 M solution in water, 0.69 mL, 11.0 mmol) was added to 5-chloro-2-(2,4-dimethylthiophen-3-yl)-3-(4-hydroxyphenyl)-1H-indole-1-carbonitrile (42 mg, 0.11 mmol) in DCM (5 mL) at 0° C. and the reaction was stirred at 0° C. for 65 h. Brine was added and the aqueous mixture was extracted with DCM. The solvent was concentrated and the crude product was purified by preparative HPLC to give 5-chloro-2-(2,4-dimethylthiophen-3-yl)-N′-hydroxy-3-(4-hydroxyphenyl)-1H-indole-1-carboximidamide (7.0 mg, 35%). 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: 414.5; 412.4 (M+H), 412.3; 409.9 (M−H); 1H NMR (acetone-d6, 500 MHz): 7.65 (d, 1H, J=2.1 Hz), 7.58 (d, 1H, J=8.8 Hz), 7.25 (dd, 1H, J=8.8, 2.1 Hz), 7.10 (m, 2H), 6.83-6.80 (m, 3H), 2.18 (s, 3H) and 1.95 (d, 3H, J=1.1 Hz).

Workup

extractionthe aqueous mixture was extracted with DCM
concentrationThe solvent was concentrated
customthe crude product was purified by preparative HPLC

Sources & evidence

ORD record: ord-07239889d79b4c7faab62a87b7e91f16
Source dataset: uspto-grants-2014_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08710243B2

Reaction notes

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