Hydrochloric Acid → HCID 59187379, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 2,3-dichloropyrazine (6-1, 3.5 g, 23.5 mmol) in MeOH (115 mL) was added NaOMe (15.0 mL, 70.5 mmol) and the system was stirred overnight. The reaction contents were then filtered through a fritted funnel of medium porosity, concentrated, and partitioned between EtOAc and water. The organic phase was washed with brine, dried over Na2SO4, filtered and concentrated to afford a clear oil. To this clear oil (2.5 g, 17.8 mmol) in DMF (17 ml) at 0° C. was added NBS (3.5 g, 19.6 mmol) the system was stirred overnight. The system was quenched with Na2SO3 and then poured into ice water. The resulting solids that precipitated from solution were isolated by filtration and dried to afford a white solid. To this white solid (1 g, 4.5 mmol) in DMF (9 mL) was added copper cyanide (0.45 g, 5.0 mmol) and heated to 185° C. for 20 minutes in the microwave reactor. The mixture was cooled and partitioned between EtOAc and water. The organic phase was washed with brine, dried over Na2SO4, filtered and concentrated. The crude material was purified by gradient elution on silica (0 to 65% EtOAc in hexanes) to afford a white powder. To this white powder (0.740 g, 4.5 mmol) in MeOH (40 mL) was added Pearlman's Catalyst (0.315 g, 0.45 mmol) and concentrated HCl (3.0 mL, 36 mmol). The system was then stirred under an atmosphere of hydrogen via a balloon for 1.5 h. The reaction contents were filtered through a pad of celite followed by removal of methanol in vacuo. The crude mixture was then dissolved in DCM, basified using saturated Na2CO3 and then extracted several times with DCM. The organic phase was washed with brine, dried over Na2SO4, filtered and concentrated to yield the desired product (6-2) as a bone solid. ESI+MS[M+H]+C7H11N3O2: M−16 (—NH2), 152.82 found, 169.2 required.

Provenance & Evidence