Methylamine → Tert-butyl 3-(2-(4-fluorophenyl)-3-(methylcarbamoyl)furo[2,3-b]pyridin-5-yl)-4-methylbenzoate

Participants

Reaction Steps

HATU (209 mg, 0.550 mmol) was added to a stirring solution of methanamine (1.2 mL, 2.4 mmol, 2M in THF), DIEA (240 μL, 1.37 mmol) and 5-(5-(tert-butoxycarbonyl)-2-methylphenyl)-2-(4-fluorophenyl)furo[2,3-b]pyridine-3-carboxylic acid (205 mg, 0.458 mmol) in DMF (4.5 mL) at rt. It was allowed to stir for 1 hour. The mixture was diluted with EtOAc and washed with sat NaCl. The organic phase was dried over Na2SO4, filtered and concentrated and was purified on silica gel (Biotage, EtOAc/hexanes gradient, fraction collection at λ=254 nm) to give the expected product tert-butyl 3-(2-(4-fluorophenyl)-3-(methylcarbamoyl)furo[2,3-b]pyridin-5-yl)-4-methylbenzoate (190 mg, 0.413 mmol, 90% yield) consistent by LCMS and NMR. 1H NMR (400 MHz, MeOD) d ppm 8.28 (1H, d, J=2.26 Hz), 8.08 (1H, d, J=2.01 Hz), 7.99-8.06 (2H, m), 7.92 (1H, dd, J=8.03, 1.76 Hz), 7.86 (1H, d, J=1.51 Hz), 7.45 (1H, d, J=8.03 Hz), 7.30 (2H, t, J=8.78 Hz), 2.95 (3H, s), 2.34 (3H, s), 1.60 (9H, s). LC-MS retention time: 2.70 min; m/z (MH+): 461. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Waters SunFire 5u C18 4.6×50 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 5 ml/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 3 min, a hold time of 1 min, and an analysis time of 4 min where solvent A was 10% acetonitrile/90% H2O/0.1% trifluoroacetic acid and solvent B was 10% H2O/90% acetonitrile/0.1% trifluoroacetic acid. MS data was determined using a Micromass Platform for LC in electrospray mode.

Provenance & Evidence