4H-Cyclopenta[b]thiophene-3-carboxylic acid, 2-amino-5,6-dihydro-, ethyl ester

light yellow to beige-brown crystalline powder

General procedure: A mixture of cyclohexanone (1.06 mL, 10 mmol), ethyl cyanoacetate (1.15 mL, 10 mmol), morpholine (0.90 mL, 10 mmol), sulphur (0.32 g, 10 mmol) in ethanol (10 mL) was stirred and refluxed for overnight. After completion of the reaction, the reaction mixture was cooled to room temperature and the solvent was removed under vacuum. The crude solid was washed with cold ethanol and filtered though sintered funnel, dried under vacuum. The crude product was dissolved in dichloromethane and washed with brine. The organic layer was collected and concentrated under low vacuum to give the compound 2a; yield: 73percent (1.83 g);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: For the synthesis of 4, 5-alkyl-2-aminothiophenes (2a–2j), the general procedures are the same as those of compound 2i. A mixture of N-benzyl-4-piperidone (1i, 380 mg, 2 mmol), malononitrile (132 mg, 2 mmol), sulfur (64 mg, 2 mmol), and basic ionic liquid (bmIm)OH (380 mg, 2.4 equiv.) was heated to 60°C for 2 h. The reaction mixture was cooled to room temperature and washed with diethyl ether or ethyl acetate (340 mL), and the organic layers were concentrated under vacuum to obtain an oily crude product. The crude product was dissolved in ether/hexane (3:1, 50 mL) mixture, insoluble material was decanted, and the organic layer was concentrated to 1/4 of the volume and kept in a refrigerator. The precipitate that formed was filtered and dried.General procedure: A mixtureof the respective aldehyde or ketone (1 eq), ethylcyanoacetate (1 eq), S8 (1.1 eq), and morpholine(1.5 eq) in EtOH (5 mL) was irradiated at 120 °C for 20 min under microwave conditions. Thereaction mixture was cooled and the solution was poured onto 20 mL ice water to yield a precipitatewhich was filtered, washed with water and dried under vacuum. The crude solid was recrystallizedfrom ethanol to yield the desired product. If the solid was not precipitated from water, extract theaqueous solution with EtOAc (2 x 15 mL) and the organic solution was washed with brine, driedover sodium sulfate and filtered. The solvent was evaporated in vacuo and recrystallized fromappropriate solvent.General procedure: To a mixture of ketone (1 eq.), ethyl cyanoacetate (4) (1 eq.), and elemental sulfur (1 eq.) in absolute ethanol (1.7 mL/mmol eq.) was added triethylamine (1.5 eq.), and the mixture was refluxed for 24 h. The reaction mixture was then concentrated and the residue was partitioned between water (10 mL/mmol eq.)and ethyl acetate (10 mL/mmol eq.). The organic layer was separated, dried over MgSO4, and concentrated, and the crude product was purified by crystallization from EtOH/H2O unless otherwise stated.#10;A solution of cyclopentanone (16.8 g, 199.72 mmol, 1.00 equiv), ethyl 2-cyanoacetate (22.6 g, 199.80 mmol, 1.00 equiv), diethylamine (14.4 g, 199.8 mmol, 1.00 equiv) and S (6.4 g, 0.2 mol, 1.00 equiv) in ethanol (250 mL) was stirred for 16 h at room temperature. General procedure: A mixture of 1 (1 mmol), 2 (1 mmol), elemental sulfur (1 mmol)and BSA (20 mg) was added to 1 mL of DMF. The reaction was incubatedat 50 C and 200 rpm. After the required time, the BSA wasfiltered off to terminate the reaction. For the products with highyields, the solid crude products precipitated in water, and then followedby filtration and drying. For the products with low yields, the crude residues were purified by flash column chromatographyon silica gel using petroleum/ethyl acetate.General procedure: A mixture of ketone (1.0 eq.), sulfur powder (1.0 eq.) and t-butyl cyanoacetate, ethyl cyanoacetate or malononitrile (1.0 eq.) in EtOH (2mL/mmol) was prepared before morpholine (1.0 eq.) was added dropwise, ensuring that the reaction did not heat up above 60°C during the addition. The mixture was then heated at 40°C and stirred for 4–20h.

Molecular Weight:211.28
XLogP3:2.7
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:3
Exact Mass:211.06669983
Monoisotopic Mass:211.06669983
Topological Polar Surface Area:80.6
Heavy Atom Count:14
Complexity:234
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes