4-Bromobenzoic acid → HCID 57345455, compound

DIPEA (0.52 mL, 3.0 mmol) was added to a stirred suspension of 4-bromobenzoic acid (462 mg, 3.0 mmol) and TBTU (963 mg, 3.0 mmol) in THF (15 mL) at rt. After 10 min was (S)-1-(2-(methylamino)butyl)azetidin-3-ol (Compound M12) (475 mg, 3.0 mmol) added, followed by addition of DIPEA (0.52 mL, 3.0 mmol). The reaction was stirred at rt for 4 h. The mixture was concentrated under reduced pressure and the residue dissolved in DCM (60 mL). The organic phase was washed with NaHCO3 (aq., 60 mL). The aqueous layer was extracted with DCM (15 mL). The combined organic layers were washed with NaHCO3 (8% aq., 60 mL), dried (Na2SO4) and concentrated under reduced pressure. The residue was purified by preparative HPLC to give the title compound (577 mg, 56%). Mixture of rotamers: 1H NMR (500 MHz, DMSO-d6) δ 0.82, 1.43-1.54, 2.43, 2.54-2.62, 2.70-2.80, 3.39-3.51, 4.18, 4.88, 7.33, 7.63. Total number of protons: 20. There is one additional very broad proton signal between 4.2 and 3.1 ppm. HRMS (M+H)+: calculated 341.0865. found 341.0870.

1. concentrationThe mixture was concentrated under reduced pressure
2. dissolutionthe residue dissolved in DCM (60 mL)
3. washThe organic phase was washed with NaHCO3 (aq., 60 mL)
4. extractionThe aqueous layer was extracted with DCM (15 mL)
5. washThe combined organic layers were washed with NaHCO3 (8% aq., 60 mL)
6. dry with materialdried (Na2SO4)
7. concentrationconcentrated under reduced pressure
8. customThe residue was purified by preparative HPLC

ORD record

ord-f94062405c8247fb8eaf6f9aa24897e7

Source dataset

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08361998B2