3-oxabicyclo[3.1.0]hexane-2,4-dione

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

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

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

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

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

Conditions: temp:180.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-(cyclohexen-1-yl)ethylamine (0.59 g) and 3-oxabicyclo[3.1.0]hexane-2,4-dione (0.5 g) was heated at 180° C. for 3 hours. The resulting mixture was cooled to room temperature to give the title compound as a yellow solid, m.p. 60-61° C. The resulting mixture was cooled to room temperature

Conditions: temp:180.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of n-octylamine (24.2 g) and 3-oxabicyclo[3.1.0]hexane-2,4-dione (20.0 g) was heated at 180° C. for 2.5 hours and was then cooled to room temperature. The mixture was distilled in vacuo (boiling point 140-142° C. @ 0.1 mmHg) to give the title compound as a colourless oil. was then cooled to room temperature The mixture was distilled in vacuo (boiling point 140-142° C. @ 0.1 mmHg)

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

Procedure: To 100 mL of ethanol is added 1-pentylpiperazine (15.6 g, 0.1 mol) and 11.2 g (0.1 mol) of 3-oxabicyclo[3.1.0]-hexane-2,4-dione. Reflux the reaction and monitor by thin-layer chromatography. Upon completion remove the solvent in vacuo to obtain the title compound. Reflux the reaction and monitor by thin-layer chromatography Upon completion remove the solvent in vacuo

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

Procedure: A solution of the compound obtained in Step C (15 mmoles) and 3-oxa-bicyclo[3.1.0]-hexane-2,4-dione (22.5 mmoles) in acetic acid (60 ml) is heated at reflux for 48 hours. The mixture is brought to ambient temperature and the solid formed is filtered off to yield the title product, which is used directly in the next reaction. at reflux for 48 hours is brought to ambient temperature the solid formed is filtered off

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

Procedure: N′-hydroxy-2-pyridinecarboximidamide (0.137 g) with 3-oxabicyclo[3.1.0]hexane-2,4-dione (0.112 g) in dimethylformamide (2 drops) was heated for 4 times 30 seconds in a CEM MARS 5 microwave at 100% of 300 W to leave a fused mass. The reaction was allowed to cool and triturated with diethyl ether and filtered to leave cis-2-[3-(2-pyridinyl)-1,2,4-oxadiazol-5-yl]cyclopropanecarboxylic acid (0.200 g). to leave a fused mass to cool triturated with diethyl ether filtered

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

Procedure: To a cold (0° C.) stirred solution of bromobenzene (9.09 g, 57.89 mmol) and AlCl3 (18.36 g, 137.84 mmol) in dry DCM (150 mL) was added 3-oxabicyclo[3.1.0]hexane-2,4-dione (5.40 g, 48.24 mmol). The reaction mixture was stirred at rt for 3 days. The dark-red solution was then poured into ice-cold water (120 mL), and conc. HCl (10 mL) was added. The solution was stirred for few minutes, and the layers were separated. The aqueous layer was extracted with DCM and the combined organic phases were washed with water, brine, dried over Na2SO4 and concentrated to give cis-2-(4-bromobenzoyl)cyclopropanecarboxylic acid (9.69 g, 65%). LC-MS ret. time 2.50; m/z 270 (MH+); 1H NMR (400 MHz, CD2Cl2) δ 1.54 (m, 1H), 1.85 (m, 1H), 2.37 (m, 1H), 2.88 (m, 1H), 7.65 (m, 2H), 7.90 (m, 2H). was added The solution was stirred for few minutes the layers were separated The aqueous layer was extracted with DCM the combined organic phases were washed with water, brine dried over Na2SO4 concentrated

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

Procedure: A solution of N-(2-aminopyridin-4-yl)-2,6-dichlorobenzamide (1.41 g, 5 mmol) and 3-oxabicyclo[3.1.0]hexane-2,4-dione (2.24 g, 20 mmol) in 1,4-dioxane (25 mL) was heated at 90° C. for 4 hours. The reaction was cooled to room temperature and the precipitated white solid was collected by filtration to give 2,6-dichloro-N-(2-(−2,4-dioxo-3-azabicyclo[3.1.0]hexan-3-yl)pyridin-4-yl)benzamide (1.28 g, yield: 68%). 1H NMR (400 MHz, DMSO-d6) δ 11.42 (s, 1H), 8.47 (d, J=5.6 Hz, 1H), 7.69 (d, J=1.8 Hz, 1H), 7.67-7.59 (m, 3H), 7.55 (dd, J=9.2, 6.8 Hz, 1H), 2.74 (dd, J=8.0, 3.6 Hz, 2H), 1.69 (ddt, J=20.6, 8.1, 4.2 Hz, 2H). LCMS (ESI) m/z: 376.0 [M+H+]. the precipitated white solid was collected by filtration