Pyrrolidine → HCID 178420445, compound

Participants

Reaction Steps

To a stirring solution of Example 48 (trans-toluene-4-sulfonic acid 3-(4-pyrrolidin-1-ylmethyl-phenyl)-cyclobutylmethyl ester) (200 mg, 0.5 mmol) in DMA (1.5 mL) was added the appropriate amine, for example pyrollidine (84 uL, 1.0 mmol). The reaction was then heated to 110 □C (oil bath). After 12 hr the reaction was cooled to rt and concentrated under reduced pressure. This material was free based by stirring in solid K2CO3 and MeOH for 2 hours. After 2 hr of stirring silica gel was added to the vessel (dry pack) and the methanolic slurry was concentrated. Purfication of this material was accomplished by flash column chromatography using a 12 g ISCO column, eluting with a gradient of 5%–10% MeOH/CH2Cl2 with 0.2% NH4OH. The product containing fractions were collected and concentrated to give the title compound as a colorless oil. The HCl salt was made by taken the freebase up in EtOAc and then adding a solution of HCl (2 eq, 1 M HCl, THF) to give a colorless solid.

Provenance & Evidence