ETHYL 2-AMINO-4-METHYLTHIOPHENE-3-CARBOXYLATE

Yellow solid

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);Acetone (200 g, 3.444 mol, 1 eq), cyanoacetic acid ethyl ester (389.5 g, 3.444 mol, 1 eq), sulfur (110.4 g, 3.444 mol, 1 eq)Anhydrous ethanol 400ml, stirring, warming to an internal temperature of 30 , temperature control 30 ~ 40 dropwise morpholine (300g, 3.444mol, 1eq), the addition was complete, warmed to 60 , incubated for 5h, TLC (EA: PE = 1: 3) until the reaction was complete. The reaction was stopped and the temperature was lowered to about 30 ° C. The reaction mixture was poured into 2 L of water and precipitated with a solid and stirred for 15 min.Filtration, the filter cake was rinsed with 200ml of 50percent ethanol in water and air-dried at 50 ° C for 4h to obtain a yellow solid II:454.2 g, yield: 71.2percent;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: 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;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.Example 201

Molecular Weight:185.25
XLogP3:2.4
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:3
Exact Mass:185.05104977
Monoisotopic Mass:185.05104977
Topological Polar Surface Area:80.6
Heavy Atom Count:12
Complexity:174
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes