Thiophene-3-carboxylic acid → N-(3-Iodo-4-methylphenyl)thiophene-3-carboxamide

Thiophene-3-carboxylic acid (2.75 g, 21.45 mmol) and HATU (8.15 g, 21.45 mmol) in DMF (25 ml) were stirred at room temperature for l5 mins. HOBT (2.9 g, 21.45 mmol), 3-iodo-4-methylaniline (5.0 g, 21.45 mmol) and DIPEA (11.2 ml, 64.35 mmol) were added and the reaction stirred at room temperature for 16 hrs. The solvent was evaporated under vacuum and the residue partitioned between ethyl acetate (100 ml) and aqueous sodium carbonate (10%, 100 ml). The aqueous layer was extracted with ethyl acetate (50 ml) and the combined organic phases washed with hydrochloric acid (2N, 75 ml), water (75 ml) and brine (75 ml). The organic phase was dried (magnesium sulphate) and absorbed onto silica. The silica was applied to a flash silica column and eluted with cyclohexane/ethyl acetate (4:1). The solvent was evaporated from the product fractions under vacuum to give N-(3-iodo-4-methylphenyl)thiophene-3-amide. LCMS: retention time 3.69 min, MH+ 344. NMR: δH [2H6]-DMSO 10.06,(1H, b), 8.34,(1H, m), 8.29,(1H, d), 7.70,(1H, dd), 7.66,(1H, dd), 7.62,(1H, dd), 7.30,(1H, d), 2.34,(3H, s).

1. customThe solvent was evaporated under vacuum
2. customthe residue partitioned between ethyl acetate (100 ml) and aqueous sodium carbonate (10%, 100 ml)
3. extractionThe aqueous layer was extracted with ethyl acetate (50 ml)
4. washthe combined organic phases washed with hydrochloric acid (2N, 75 ml), water (75 ml) and brine (75 ml)
5. dry with materialThe organic phase was dried (magnesium sulphate)
6. customabsorbed onto silica
7. washeluted with cyclohexane/ethyl acetate (4:1)
8. customThe solvent was evaporated from the product fractions under vacuum

ORD record

ord-abbff8343f9d43529b6dd6a5e0a57cd4

Source dataset

uspto-grants-2012_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08252818B2