2-amino-2-cyclopropylpropanenitrile

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

Procedure: 3-(Chloromethyl)benzoyl chloride (9.08 mmol, 1.290 ml, 1.716 g) and triethylamine (27.2 mmol, 3.79 mL, 2.76 g) were stirred in dichloromethane (10 mL) at 0° C. 2-Amino-2-cyclopropylpropanenitrile (9.08 mmol, 1 g) was added dropwise and the reaction allowed to warm to room temperature and stir for 1 hour. The reaction mixture was washed with water and the organic phase concentrated under vacuum to afford the title compound (1.451 g). MS (ESI) m/z 263.1 [M+H]+ The reaction mixture was washed with water the organic phase concentrated under vacuum

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

Procedure: The title compound was synthesized in analogy to Example 78e, using 5-Bromo-4-((S)-2,2,2-trifluoro-1-methyl-ethoxy)-pyridine-2-carboxylic acid (Example 96d) and 2-amino-2-cyclopropylpropanenitrile (CAN 37024-73-0) as starting materials and isolated (607 mg, 65%) as a yellow oil; MS (ESI, m/z): 420.4 (M+H+). isolated (607 mg, 65%) as a yellow oil

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

Procedure: To a solution of 5-Bromo-4-(2,2,2-trifluoro-ethoxy)-pyridine-2-carboxylic acid (Example 78d, 1.0 g, 3.33 mmol) dry DMF (15 ml) were added TBTU (1.12 g, 3.5 mmol) and triethylamine (675 mg, 929 μl, 6.67 mmol). The reaction mixture was stirred at room temperature for 30 minutes followed by addition of 2-amino-2-cyclopropylpropanenitrile (CAN 37024-73-0, 404 mg, 3.67 mmol). The reaction was stirred at room temperature for 18 hours. The reaction mixture was poured into a separatory funnel, diluted with ethylacetate and extracted with an 1.0M aqueous solution of sodium bicarbonate. The organic phase was collected and the aqueous phase was back-extracted with ethylacetate. The organic phases were combined, dried over sodium sulfate and evaporated down to dryness. The crude material was purified by flash chromatography on silica eluting a heptane/ethylacetate gradient to yield the title compound (910 mg, 70%) as a light yellow oil. MS (ESI, m/z): 392.3 (M+H+). The reaction was stirred at room temperature for 18 hours The reaction mixture was poured into a separatory funnel extracted with an 1.0M aqueous solution of sodium bicarbonate The organic phase was collected the aqueous phase was back-extracted with ethylacetate dried over sodium sulfate evaporated down to dryness The crude material was purified by flash chromatography on silica eluting a heptane/ethylacetate gradient