2-AMINO-4,7-DIHYDRO-5H-THIENO[2,3-C]PYRIDINE-3,6-DICARBOXYLIC ACID 6-TERT BUTYL ESTER 3-ETHYL ESTER

2-Amino-4, 7-dihydro-5H-thieno[2, 3-c]pyridine-3, 6-dicarboxylic acid 6-tert-butyl ester 3-ethyl ester (step a). To a mixture of 4-oxo-piperidine-1-carboxylic acid tert-butyl ester (12.9 g), ethyl cyanoacetate (7.345 g), and sulphur (2.080 g) in absolute ethanol (50 mL) was added triethylamine (9 mL). After stirring for 16 h, the precipitate was collected by filtration and washed with ethanol to give the title compound (18.7 g, 88percent). tert-Butyl 4-oxopiperidine-l-carboxylate (101 g, 505 mmol) was dissolved in ethanol (806 mL), and ethyl cyanoacetate (57.2 g, 505 mmol) and sulfur (17.0 g, 531 mmol) were added. The mixture was stirred for a couple of minutes, and then morpholine (44.0 g, 505 mmol) was added. The reaction was stirred at rt overnight. The precipitate was collected by suction filtration and washed with ethanol to yield 142 g (86percent) of the title compound.To a 1-Boc-4-piperidone (25.0 g, 123 mmol) in ethanol (100 mL) solution were added ethyl cyanoacetate (14.2 g, 123 mmol, 1 equiv), diethylamine (12.72 mL, 123 mmol, 1 equiv), and sulfur (4.14 g, 129 mmol, 1.05 equiv). The reaction was stirred at room temperature for 16 h then filtered and washed with ethanol (25 mL) to obtain a white solid (33.11 g, 102 mmol, 83percent). General procedure: A mixture of the ketone (1 eq.), cyanoacetate (1 eq.), and elemental sulphur (1eq.) in ethanol were combined and heated at 40-70 °C. Morpholine or diethylamne (1 eq.) was added dropwise. The reaction was stirred at 40-70 °C for 1-4 hours, and then stirred at room temperature overnight. The resulting precipitate was typically collected by filtration and recrystallised from ethanol or toluene.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);

Molecular Weight:326.4
XLogP3:2.8
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:6
Rotatable Bond Count:5
Exact Mass:326.13002836
Monoisotopic Mass:326.13002836
Topological Polar Surface Area:110
Heavy Atom Count:22
Complexity:438
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes