2-Amino-5-methyl-3-thiophenecarbonitrile

General procedure: A mixture of 0.070 g 4-propylcyclohexanone (0.5 mmol), 0.030 g malononitrile (0.5 mmol), 0.019 g sulfur powder(0.6 mmol), and 0.1 cmGeneral procedure: General procedure forpreparation of2‑aminothiophenesFor a general synthesis see He, X.; Griesser, U. J.; Stowell, J. G.; Borchrdt, T. B.; Byrn, S. R. J. Pharm. Sci. 2001, 90, 371.A Sulfur (STriethylamine (33.3 g, 0.33 mol) was added dropwise to a mixture of sulfur (16.0 g, 0.50 mol) and propionaldehyde (34.8 g, 0.60 mol) in DMF (100 mL) under vigorous stirring in an ice bath. The reaction mixture was stirred for 40 min at 0 °C, and stirred another 120 min at 15–20 °C. Then malononitrile (33.7 g, 0.51 mol) in DMF (66 mL) was added dropwise in an ice bath. The reaction mixture was stirred for additional 80 min at 15–20 °C, and was poured into an ice-water (300 mL) with stirring. The resulted precipitate was filtered, washed with ice-water, and dried in vacuo to obtain an orange solid product (37.0 g). The resulted solution was extracted with EtOAc (200 mL × 3), washed with water, dried over NaA mixture of sulfur (21.8 g), propionaldehyde (47.3 g) and N, N- DIMETHYLFORMAMIDE (135 mL) was placed in a 500 mL flask and cooled in an ice bath. Triethylamine (57.6 mL) was added dropwise over 30 minutes to the stirred reaction mixture and the temperature was maintained between 5-10°C. The pot was warmed to 18°C, and stirred at 182 C over 50 minutes. A solution of malononitrile (45 g) in N, N-DIMETHYLFORMAMIDE (90 mL) was added dropwise at a temperature of 182°C. After the addition was complete, the mixture was stirred at 18I2°C for 45 minutes. The mixture was poured onto ice/water (1.2 L) while stirring. A solid precipitate was collected by filtration, washed thoroughly with water, and dried overnight in vacuo at 70°C, (or fan-dried at 45°C) to give 2- amino-5-methylthiophene-3-carbonitrile (58.5 g). Yield: 62.3percent.General procedure: 10 mmol of ketone or aldehyde, 10 mmol of malonodinitrile, and 10 mmol of sulfur powder were mixed. Then, 0.02 g (2.5 molpercent) of ZnO nano-particles was added and the mixture was heated to 100 °C with good stirring for the required time. After 6 h, the reaction was stopped and the corresponding product was worked up by 10 ml of ethanol and ZnO was separated by a simple filtration. Thereafter, the reaction mixture was cooled to room temperature and poured into 150 ml of ice-water. The precipitate was filtered off, washed with cold water and dried. To further purification, the crude product was purified by silica gel column chromatography with 10:1 hexane:ethyl acetate as eluent.2-Methyl-4-(4-methylpiperazin-1-yl)-10H-benzo[b]thieno[2, 3-e][1, 4]diazepine Step 1 2-Amino-5-methylthiophene-3-carbonitrile: At about -5° C. and over a period of about 15 minutes, triethylamine (22.97 g, 227 mmol) was added dropwise to a mixture of sulphur powder (12.13 g, 378.35 mmol), propionaldehyde (26.34 g, 454.1 mmol) and N, N-dimethylformamide (100 mL). The mixture was stirred at about 18° C. for about 2 hours, and then a solution of malononitrile (25 g, 378.44 mmol) and N, N-dimethylformamide (50 mL) was added dropwise over a period of about 20 minutes. The mixture was stirred at about 18° C. for about 90 minutes, and then poured into ice-cold water. The resulting precipitant was collected and dried to give the title product as a cream color solid (25 g, yield=48percent). m.p. 93-95° C. General procedure: A mixture of carbonyl compounds 4a-r (3.0 mmol), dicyanomethane (3.3 mmol), sulfur (4.5 mmol), and imidazole (0.3 mmol) in DMF (3.0 mL) was stirred at 60 °C under nitrogen atmosphere for 10-18 h. The crude materials were directly purified through flash chromatography to give the desired products 5a-r.

An Impurity generated in the preparation of Olanzapine (O253750).

Molecular Weight:138.19
XLogP3:1.9
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Exact Mass:138.02516937
Monoisotopic Mass:138.02516937
Topological Polar Surface Area:78
Heavy Atom Count:9
Complexity:148
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes