3,4-Dimethylbenzoic acid → HCID 57345465, compound

Participants

Reaction Steps

3,4-Dimethylbenzoic acid (0.174 g, 1.16 mmol), TBTU (0.373 g, 1.16 mmol) and DIPEA (0.303 mL, 1.74 mmol) was stirred in DCM (2 mL) for 40 min before (S)-1-(2-(methylamino)pentyl)azetidin-3-ol (Compound J4) (0.1 g, 0.58 mmol) was added. The resultant mixture was stirred at rt overnight. The solvent was removed under reduced pressure and the residue dissolved in a mixture of MeOH (3 mL) and NaOH (aq. 1 mL, 1M). The resultant mixture was stirred at rt for 90 min before the MeOH was removed on a vacuum centrifuge. The crude product was extracted with DCM and concentrated under reduced pressure. To the residue was DMSO (1 mL), DCM (3 mL) and KOH (1M solution, 3 mL) added. The organic phase was filtered through a phase separator and concentrated under reduced pressure. The residue was purified by preparative HPLC. The product containing fractions was concentrated, water (5 mL) and DCM (5 mL) was added and the pH was adjusted to 12 using KOH (1M solution). The organic layer was filtered through a phase separator and the solvent was removed under reduced pressure to give the title compound (48 mg, 27%). Mixture of rotamers: (600 MHz, DMSO-d6) δ 0.69-0.78, 0.85-0.93, 0.94-1.06, 1.08-1.50, 2.19-2.28, 2.32-2.41, 2.44-2.56, 2.56-2.65, 2.66-2.76, 3.27-3.38, 3.43-3.55, 4.03-4.20, 4.44-4.52, 5.17-5.26, 6.97-7.21. Total no of protons: 28. HRMS (M+H)+: calculated 305.2229. found 305.2214.

Provenance & Evidence