N'-hydroxy-2-methoxybenzenecarboximidamide

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a reactor tube, a mixture of N′-hydroxy-2-methoxybenzamidine (598 mg, 3.6 mmol), 4-pentynoic acid (350 mg, 3.6 mmol), HOBT (0.55 g, 3.6 mmol) and EDCI.HCl (1.03 g, 5.4 mmol) in dioxane (7.4 mL) was stirred at R.T for 3 h. After this time the mixture was heated at 80° C. overnight in a reaction block. The mixture was concentrated and the crude product was purified by flash chromatography (Prepacked column 25 g with DCM as eluent) to afford 299 mg of 5-(but-3-ynyl)-3-(2-methoxyphenyl)-1,2,4-oxadiazole (36%) as yellow oil. The mixture was concentrated the crude product was purified by flash chromatography (Prepacked column 25 g with DCM as eluent)

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

Procedure: Oxalyl chloride (139 μL; 1.64 mmol; 3 eq.), Intermediate 33 (120 mg; 0.55 mmol; 1 eq.), Intermediate 1 (91 mg; 0.55 mmol, 1 eq.) and DIEA (283 μL; 1.64 mmol; 3 eq.) were reacted according to general procedure 2. Purification by preparative HPLC (increasing amount of 0.1% TFA in CH3CN, in 0.1% TFA in water) afforded the title compound as an orange solid. Purification by preparative HPLC (increasing amount of 0.1% TFA in CH3CN, in 0.1% TFA in water)

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

Procedure: Oxalyl chloride (138 μL; 1.63 mmol; 3 eq.), Intermediate 35 (120 mg; 0.54 mmol; 1 eq.), Intermediate 1 (90 mg; 0.54 mmol, 1 eq.) and DIEA (280 μL; 1.63 mmol; 3 eq.) were reacted according to general procedure 2. Purification by column chromatography c-hexane/ethyl acetate, 95/5) afforded the title compound as a yellow solid. Purification by column chromatography c-hexane/ethyl acetate, 95/5)

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

Procedure: Oxalyl chloride (109 μL; 1.28 mmol; 3 eq.), Intermediate 34 (120 mg; 0.43 mmol; 1 eq.), Intermediate 1 (71 mg; 0.43 mmol, 1 eq.) and DIEA (95 μL; 1.28 mmol; 3 eq.) were reacted according to general procedure 2. Purification by column chromatography c-hexane/ethyl acetate, 95/5) afforded the title compound as a white solid. Purification by column chromatography c-hexane/ethyl acetate, 95/5)

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

Procedure: Oxalyl chloride (190 mg; 1.5 mmol; 3 eq.), Intermediate 42 (137 mg; 0.5 mmol; 1 eq.), Intermediate 1 (83 mg; 0.5 mmol, 1 eq.) and DIEA (194 mg; 1.5 mmol; 3 eq.) were reacted according to general procedure 2. Purification by crystallisation from n-pentane afforded the title compound as a white solid. Purification by crystallisation from n-pentane

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

Procedure: Oxalyl chloride (106 μL; 1.26 mmol; 3 eq.), Intermediate 32 (120 mg; 0.42 mmol; 1 eq.), Intermediate 1 (70 mg; 0.42 mmol, 1 eq.) and DIEA (217 μL; 1.26 mmol; 3 eq.) were reacted according to general procedure 2. Purification by column chromatography c-hexane/ethyl acetate, 95/5) followed by crystallization from n-pentane afforded the title compound as a yellow solid. Purification by column chromatography c-hexane/ethyl acetate, 95/5) followed by crystallization from n-pentane

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

Procedure: Oxalyl chloride (190 mg; 1.5 mmol; 3 eq.), Intermediate 31 (149 mg; 0.5 mmol; 1 eq.), Intermediate 1 (83 mg; 0.5 mmol, 1 eq.) and DIEA (194 mg; 1.5 mmol; 3 eq.) were reacted according to general procedure 2. Purification by column chromatography c-hexane/ethyl acetate, 50/50) followed by crystallisation from Et2O/n-pentane afforded the title compound as a yellow solid. Purification by column chromatography c-hexane/ethyl acetate, 50/50) followed by crystallisation from Et2O/n-pentane

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

Procedure: Oxalyl chloride (132 μL; 1.56 mmol; 3 eq.), Intermediate 30 (120 mg; 0.52 mmol; 1 eq.), Intermediate 1 (86 mg; 0.52 mmol, 1 eq.) and DIEA (268 μL; 1.56 mmol; 3 eq.) were reacted according to general procedure 2. Purification by column chromatography c-hexane/ethyl acetate, 80/20) afforded the title compound as an orange foam. Purification by column chromatography c-hexane/ethyl acetate, 80/20)

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

Procedure: Oxalyl chloride (120 μL; 1.45 mmol; 3 eq.), Intermediate 29 (120 mg; 0.48 mmol; 1 eq.), Intermediate 1 (80 mg; 0.48 mmol, 1 eq.) and DIEA (250 μL; 1.45 mmol; 3 eq.) were reacted according to general procedure 2. Purification by precipitation from DCM/n-pentane afforded the title compound as a white solid. Purification by precipitation from DCM/n-pentane

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

Procedure: Oxalyl chloride (112 μL; 1.32 mmol; 3 eq.), Intermediate 28 (120 mg; 0.44 mmol; 1 eq.), Intermediate 1 (73 mg; 0.44 mmol, 1 eq.) and DIEA (228 μL; 1.32 mmol; 3 eq.) were reacted according to general procedure 2. Purification by precipitation from DCM/n-pentane afforded the title compound as a yellow solid. Purification by precipitation from DCM/n-pentane

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

Procedure: Oxalyl chloride (126 μL; 1.49 mmol; 3 eq.), Intermediate 27 (120 mg; 0.5 mmol; 1 eq.), Intermediate 1 (82 mg; 0.5 mmol, 1 eq.) and DIEA (256 μL; 1.49 mmol; 3 eq.) were reacted according to general procedure 2. Purification by precipitation from DCM/n-pentane afforded the title compound as a brown solid. Purification by precipitation from DCM/n-pentane