1,2-Dichloroethane → 5-chloro-N-methoxy-N-methyl-1H-indole-2-carboxamide

HRID 1818615Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([C:11]([OH:13])=O)=[CH:5]2.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.Cl.[CH3:29][NH:30][O:31][CH3:32].CCN(C(C)C)C(C)C.C(=O)(O)[O-].[Na+]>CN(C)C=O>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([C:11]([N:30]([O:31][CH3:32])[CH3:29])=[O:13])=[CH:5]2

Participants

Conditions

Temperature: 40 °C

Procedure

To a flask containing 5-chloroindole-2-carboxylic acid (8.33 g, 42.6 mmol) were added EDC (12.6 g, 63.9 mmol), HOBt (8.63 g, 63.9 mmol), N,O-dimethylhydroxylamine hydrochloride (6.23 g, 63.9 mmol) sequentially. N,N-Dimethylformamide (100 mL) was added, followed by DIEA (22.6 mL, 128 mmol), and the resulting solution was stirred at 40° C. for 18 h. The reaction mixture was allowed to cool to room temperature, then was poured into saturated aqueous sodium bicarbonate and extracted with ethyl acetate. The combined organic phases were dried over anhydrous sodium sulfate and concentrated in vacuo. The resulting amide was taken forward without further purification: LCMS B, tr=2.03 min, m/z 239.1 [M+H]+; 1H NMR (500 MHz, CDCl3) δ 9.55 (s, 1H), 7.66 (d, J=2.0 Hz, 1H), 7.37 (d, J=8.5 Hz, 1H), 7.24 (dd, J=8.5, 2.0 Hz, 1H), 7.16 (s, 1H), 3.85 (s, 3H), 3.44 (s, 3H).

Workup

temperatureto cool to room temperature
extractionextracted with ethyl acetate
dry with materialThe combined organic phases were dried over anhydrous sodium sulfate
concentrationconcentrated in vacuo
customThe resulting amide was taken forward without further purification
customLCMS B, tr=2.03 min, m/z 239.1 [M+H]+

Sources & evidence

ORD record: ord-13f86a5687bb4cf4aef89b0a649cc2da
Source dataset: uspto-grants-2009_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07598398B2

Reaction notes

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