2-(3-aminooxetan-3-yl)acetamide

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

Procedure: The title compound was synthesized in analogy to Example 112e, using 5-(3,3-difluoroazetidin-1-yl)-4-(2,2,2-trifluoroethoxy)pyridine-2-carboxylic acid (Example 223b) and 2-(3-Amino-oxetan-3-yl)-acetamide (CAN 1417638-25-5) as starting material and isolated (42 mg, 31%); MS (ESI, m/z): 425.5 (M+H+). isolated (42 mg, 31%)

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

Procedure: The title compound was synthesized in analogy to Example 112e, using 4-Cyclopropylmethoxy-5-(3,3-difluoro-azetidin-1-yl)-pyridine-2-carboxylic acid (Example 53e) and 2-(3-Amino-oxetan-3-yl)-acetamide (CAN 1417638-25-5) as starting material and isolated (31 mg, 36%); MS (ESI, m/z): 397.6 (M+H+). isolated (31 mg, 36%)

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

Procedure: To a solution of 4-chloro-5-cyclopropyl-pyridine-2-carboxylic acid (Example 48b, 200 mg, 1.01 mmol) in DMF (4.0 ml) were added TBTU (357 mg, 1.11 mmol) and DIEA (654 mg, 866 μl, 5.06 mmol) and the reaction mixture was stirred at room temperature for 20 minutes. Addition of 2-(3-aminooxetan-3-yl)acetamide (158 mg, 1.21 mmol) and the reaction was stirred at room temperature for 18 hours. The reaction mixture was diluted with ethyl acetate and extracted with water. The organic phase was collected, dried over sodium sulfate and evaporated down to dryness. The crude material was purified by flash chromatography on silica, eluting with a ethyl acetate/heptane gradient to yield the title compound (80 mg, 26%) as a yellow solid. MS (ESI, m/z): 310.0 (M+H+). the reaction was stirred at room temperature for 18 hours extracted with water The organic phase was collected dried over sodium sulfate evaporated down to dryness The crude material was purified by flash chromatography on silica eluting with a ethyl acetate/heptane gradient

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

Procedure: To a microwave tube was added ethyl 2-(3-aminooxetan-3-yl)acetate (CAN 1207175-54-9, 400 mg, 2.51 mmol) followed by toluene (8.0 ml) and 25% ammonium hydroxide (7.2 g, 8.0 ml, 51.4 mmol). The tube was sealed and the reaction mixture was stirred vigorously at room temperature for 6 days. The reaction mixture was concentrated in vacuo and azeotroped several times with 20 ml toluene. The crude solid was dried under high-vacuum at 40° C. to dryness to yield the title compound (290 mg, 89%) as a white solid. MS (ESI, m/z): 131.1 (M+H+). The tube was sealed The reaction mixture was concentrated in vacuo azeotroped several times with 20 ml toluene The crude solid was dried under high-vacuum at 40° C. to dryness

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

Procedure: The title compound was synthesized in analogy to Example 6 using 5-cyclopropyl-6-cyclopropylmethoxy-pyrazine-2-carboxylic acid (Example 10 g, 50 mg, 0.21 mmol) and 2-(3-amino-oxetan-3-yl)-acetamide (31 mg, 0.24 mmol) as starting materials and isolated (30 mg, 41%) as white solid; LC-MS (UV peak area, ESI) 100%, 347.1710 (M+H)+. isolated (30 mg, 41%) as white solid