Acetic Acid → HCID 68008713, compound

Participants

Reaction Steps

4-Fluoroaniline (0.032 mL, 0.34 mmol) was added to a stirred solution of 3-(2-oxo-ethyl)-5-phenoxymethyl-pyridine-2-carboxylic acid methyl ester (80 mg, 0.28 mmol, from step 7) in DCM (4 mL). The mixture was stirred at RT for 1 h. Sodium triacetoxyborohydride (89 mg, 0.42 mmol) was added and the mixture was stirred at RT for 16 h. Acetic acid (0.040 mL) was added and the mixture was stirred at RT for additional 20 h. The mixture was diluted with DCM and washed with a saturated solution of NaHCO3 and brine. The organic layer was separated, dried (Na2SO4), filtered and the solvents evaporated in vacuo. The crude product was purified by flash column chromatography (silica; 7N solution of ammonia in methanol in DCM 0/100 to 4/96). The desired fractions were collected and the solvents evaporated in vacuo to yield an impure fraction which was re-purified by RP-HPLC on (C18 XBridge, 19×100, 5 μm; 80%/0.1% NH4CO3H/NH4OH pH 9 solution in water, 20% CH3CN to 0%/0.1% NH4CO3H/NH4OH pH 9 solution in water, 100% CH3CN), to yield 7-(4-fluoro-phenyl)-3-phenoxymethyl-6,7-dihydro-[1,7]-naphthyridin-8(5H)-one (14.86 mg, 15% yield) as a white solid: 1H NMR (500 MHz, CDCl3) δ 3.22 (t, J=6.4, 2 H), 4.01 (t, J=6.4, 2 H), 5.17 (s, 2 H), 6.98 (d, J=7.8, 2 H), 7.01 (t, J=7.5, 1 H), 7.07-7.16 (m, 2 H), 7.29-7.35 (m, 2 H), 7.36-7.42 (m, 2 H), 7.76 (br. s, 1 H), 8.78 (d, J=1.7, 1 H); LC-MS (M+H)=349.1.

Provenance & Evidence