Acetic Acid → HCID 58147291, compound

To a vial charged with trimethylacetic acid (0.016 g, 0.152 mmol), HATU (0.058 g, 0.152 mmol), DCM (2 mL) and N,N-dimethylformamide (0.2 mL) was added triethylamine (0.06 mL, 0.434 mmol). The solution was shaken at room temperature for 15 min whereupon a premixed solution of methyl 2,3,4,5-tetrahydro-1H-2-benzazepine-7-carboxylate hydrochloride (0.035 g, 0.145 mmol) and triethylamine (0.06 mL, 0.434 mmol) in N,N-dimethylformamide (0.5 mL) was added. The reaction mixture was stirred at room temperature for 6 h. To the solution was added dichloroethane (1 mL) and saturated aqueous NaHCO3 solution. Upon separation, the aqueous phase was extracted with DCE (2×2 mL). The combined organic phases were dried over anhydrous MgSO4, and concentrated to give a solid residue. To the material obtained was added potassium hydroxide (0.049 g, 0.869 mmol), hydroxylamine hydrochloride (0.03 g, 0.434 mmol) and MeOH (2 mL). The resulting mixture was heated at 80° C. with vigorous shaking for 1 h. Upon cooling to room temperature, acetic acid (65.9 μL, 1.16 mmol) (50% v/v in MeOH) was added and the solution was shaken at room temperature for an additional 10 min. The solvent was then completely evaporated, the solid residue was dissolved in DMSO (1.3 mL) and subjected to prep HPLC separation [238 nm, rt=5.59 min (12 min), 20-45% MeCN—H2O gradient] to give the title compound (0.0188 g, 44.7%) as a white solid. LCMS: (FA) ES+ 291. 1H NMR (MeOD, 300 MHz) δ 7.55 (m, 1H), 7.49 (dd, J=7.8, 1.8 Hz, 1H), 7.39 (d, J=7.8 Hz, 1H), 4.57 (br, 2H), 4.01 (br, 2H), 3.08 (br, 2H), 1.86 (br, 2H), 1.21 (s, 9H).

1. additionwas added
2. customUpon separation
3. extractionthe aqueous phase was extracted with DCE (2×2 mL)
4. dry with materialThe combined organic phases were dried over anhydrous MgSO4
5. concentrationconcentrated
6. customto give a solid residue
7. customTo the material obtained
8. temperatureThe resulting mixture was heated at 80° C.
9. stirringwith vigorous shaking for 1 h
10. temperatureUpon cooling to room temperature
11. stirringthe solution was shaken at room temperature for an additional 10 min
12. customThe solvent was then completely evaporated
13. dissolutionthe solid residue was dissolved in DMSO (1.3 mL)
14. customHPLC separation [238 nm, rt=5.59 min (12 min), 20-45% MeCN—H2O gradient]

ORD record

ord-ba46412a836e4a01bbdd3d19b8a87793

Source dataset

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09096518B2