Acetic Acid → HCID 66938762, compound

Participants

Reaction Steps

Under an inert atmosphere, stir a mixture of 2-chloro-4-fluoro-N-(3-amino-4-fluorophenyl)benzamide (Preparation 14, 481 mg, 1.7 mmol), 1-methyl-4-piperidone (384 mg, 0.42 mL, 3.4 mmol), 1,2-dichloroethane (15 mL), powdered molecular sieves 4 Å (1 g) for 15 min. Add glacial acetic acid (306 mg, 0.3 mL, 5.1 mmol). After 1 hr., add sodium triacetoxyborohydride (900 mg, 4.25 mmol). Allow the reaction to go overnight. Pour the reaction mixture into ethyl acetate (200 mL), and wash once with aqueous NaOH (2N, 30 mL). Separate the organic layer, dry over anhydrous sodium sulfate, remove the solvent under reduced pressure. Further purify the residue by chromatography on silica gel using a 4%-6% gradient of (2M NH3 in methanol) in CH2Cl2 to obtain the free base of the title compound (443 mg, 69% yield). Convert the product to its HCl salt by dissolving it in CH2Cl2 and treating with excess 1.0M HCl in diethyl ether. Add more ether to precipitate the title compound as a white solid: mass spectrum (ion spray): m/z=380.2 (M+1); Analysis calculated C19H20ClF2N3O.HCl.H2O: C, 52.54; H, 5.34; N, 9.68. Found: C, 52.93; H, 5.29; N, 9.65; LY 653915: 1H NMR δ (methanol-d) 7.72 (dd, 1H), 7.60 (m, 1H), 7.37 (dd, 1H), 7.14 (m, 3H), 3.74 (m, 1H), 3.62 (d, 2H), 3.30 (dd, 2H), 2.88 (s, 3H), 2.36 (d, 2H), 1.93 (m, 2H)

Provenance & Evidence