4-ethylcyclohexan-1-amine

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (3S,6R)-1-[2-amino-6-(4-cyano-3-fluorophenyl)-4-pyrimidinyl]-6-methyl-3-piperidinecarboxylic acid (170 mg, 0.478 mmol) and HATU (218 mg, 0.574 mmol) in DMF (3 mL) was added Hunig's base (0.167 mL, 0.957 mmol), and the resulting mixture was stirred at room temperature for 15 minutes. 4-Ethylcyclohexanamine (61 mg, 0.48 mmol) was added, and the reaction mixture was stirred at room temperature for 0.5 hours. LCMS showed reaction was completed. The reaction was poured into water, and EtOAc was added to extract the product. The product stayed in the EtOAc layer. The organic layer solution was concentrated, and the formed solid was recrystallized from CH3CN to afford the title compound (187 mg) as a light yellow solid. LC-MS (ES) m/z=465 [M+H]+. the reaction mixture was stirred at room temperature for 0.5 hours reaction was added to extract the product The organic layer solution was concentrated the formed solid was recrystallized from CH3CN

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Ethyl 3-(dimethylamino)-2-isocyanoacrylate (2.00 g) was dissolved in 4-ethylcyclohexylamine (3.37 g), and the solution was stirred at 70° C. for 4.5 hours. To the reaction solution, saturated aqueous ammonium chloride was added, and organic matter was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and filtered, and the solvent was distilled off under reduced pressure to obtain a crude product. Lithium aluminum hydride (92%, 0.490 g) was suspended in tetrahydrofuran (12 mL). The produced crude product was dissolved in tetrahydrofuran (12 mL), and this solution was slowly added dropwise to the suspension at 0° C. After stirring at 0° C. for 30 minutes, the reaction solution was diluted with diethyl ether, and saturated aqueous sodium sulfate was added thereto. After stirring at room temperature for 1 hour, the formed inorganic salt was removed by filtration through celite. The filtrate was concentrated under reduced pressure to obtain a crude product. This crude product was purified by silica gel column chromatography (eluting solvent: methylene chloride-methylene chloride/methanol=9/1) to obtain the title compound (1.35 g, diastereomeric mixture, trans:cis=4:1). organic matter was extracted with ethyl acetate The organic layer was dried over anhydrous sodium sulfate filtered the solvent was distilled off under reduced pressure to obtain a crude product The produced crude product this solution was slowly added dropwise to the suspension at 0° C After stirring at 0° C. for 30 minutes was added After stirring at room temperature for 1 hour the formed inorganic salt was removed by filtration through celite The filtrate was concentrated under reduced pressure to obtain a crude product This crude product was purified by silica gel column chromatography (eluting solvent: methylene chloride-methylene chloride/methanol=9/1)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In the same manner as the synthesis of Compound 1, methyl 3-amino-4-phenylthiophene-2-carboxylate (100 mg, 0.43 mmol), triethyl orthoformate (1.0 ml), 4-ethylcyclohexanamine (0.133 ml, 0.90 mmol), and acetic acid (0.1 ml) were used to give 6.8 mg (0.02 mmol, 4.7% yield) of the title compound.