4-Methylmorpholine → HCID 57345451, compound

4-Fluoro-3-methylbenzoic acid (0.095 g, 0.62 mmol), TBTU (0.226 g, 0.70 mmol) and 4-methylmorpholine (0.194 mL, 1.76 mmol) was mixed in DMF (2 mL). After 30 min at rt was (S)-1-(2-cyclopropyl-2-(methylamino)ethyl)azetidin-3-ol (Compound J3) (0.1 g, 0.59 mmol) added. The resultant mixture was stirred at rt overnight. Analysis by LCMS indicated formation of both mono and diacylated product. Additional TBTU (0.189 g, 0.59 mmol), 4-fluoro-3-methylbenzoic acid (0.091 g, 0.59 mmol) and NMM (0.129 mL, 1.17 mmol) were added to drive the reaction towards the diacylated product. The resultant mixture was stirred at rt overnight. The mixture was diluted with DCM (5 mL) and the organic phase was washed with NaHCO3 (saturated, 5 mL), filtered through a phase separator and concentrated under reduced pressure. The residue was dissolved in a mixture of MeOH (3 mL) and NaOH (aq. 3 mL, 1M) and the resultant mixture stirred at rt for 30 min. The solvents were evaporated and the crude mixture purified by preparative HPLC to give the title compound (54 mg, 30%). Mixture of rotamers: 1H NMR (400 MHz, CD3OD) δ −0.13-1.25, 2.01-2.48, 2.60-2.65, 2.73-3.22, 3.39-4.02, 4.21-4.45, 6.96-7.45. Total no of protons: 22. HRMS (M+H)+: calculated 307.1822. found 307.1827.

1. customthe reaction towards the diacylated product
2. washthe organic phase was washed with NaHCO3 (saturated, 5 mL)
3. filtrationfiltered through a phase separator
4. concentrationconcentrated under reduced pressure
5. dissolutionThe residue was dissolved in a mixture of MeOH (3 mL) and NaOH (aq. 3 mL, 1M)
6. customThe solvents were evaporated
7. customthe crude mixture purified by preparative HPLC

ORD record

ord-bda13d219d294dcb9046041ea199a165

Source dataset

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08361998B2