Dichloromethane → 4-(4-Bromophenyl)-5-chloro-2-(2-cyano-acetylamino)-thiophene-3-carboxylic acid ethyl ester
Reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:10]([C:11]2[CH:16]=[CH:15][C:14]([Br:17])=[CH:13][CH:12]=2)=[CH:9][S:8][C:7]=1[NH2:18])=[O:5])[CH3:2].C(N(CC)CC)C.[C:26]([CH2:28][C:29](Cl)=[O:30])#[N:27].C(Cl)[Cl:33]>>[CH2:1]([O:3][C:4]([C:6]1[C:10]([C:11]2[CH:16]=[CH:15][C:14]([Br:17])=[CH:13][CH:12]=2)=[C:9]([Cl:33])[S:8][C:7]=1[NH:18][C:29](=[O:30])[CH2:28][C:26]#[N:27])=[O:5])[CH3:2]Participants
Procedure
To a cold (0° C.) solution of 2-amino-4-(4-bromophenyl)-thiophene-3-carboxylic acid ethyl ester (1.0 g, 3.1 mmol) and triethylamine (0.64 mL, 4.60 mmol) in methylene chloride (6 mL) was added cyanoacetic acid chloride (6.82 mL, 3.41 mmol, 0.5 M in methylene chloride). The cold bath was removed, and the reaction was stirred for 2 h. Saturated aqueous sodium bicarbonate solution (5 mL) was added to the reaction at room temperature. The layers were separated, and the aqueous was extracted with additional methylene chloride (3×5 mL). The combined organic layers were dried with anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to provide the titled compound as a yellow solid. MS (ESI) m/e 393 (M−H)−, NMR (300 MHz, CDCl3): δ ppm 12.0 (br s, 1H), 7.47 d, 2H), 7.16 (d, 2H), 6.68 (s, 1H), 4.16 (q, 2H), 3.69 (s, 2H), and 100 (t, 3H).
Workup
- customThe cold bath was removed
- additionSaturated aqueous sodium bicarbonate solution (5 mL) was added to the reaction at room temperature
- customThe layers were separated
- extractionthe aqueous was extracted with additional methylene chloride (3×5 mL)
- dry with materialThe combined organic layers were dried with anhydrous sodium sulfate
- filtrationfiltered
- concentrationconcentrated under reduced pressure
Sources & evidence
- ORD record
- ord-4ceb0d17efce441b909e94ee92ebf018
- Source dataset
- uspto-grants-2006_10
- Patent number
- US07119205B2
Reaction notes
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