Methylamine → 5-(benzyloxy)-2-(4-fluorophenyl)-N-methylfuro[2,3-c]pyridine-3-carboxamide

Methanamine (3.1 mL, 6.2 mmol, 2M in THF) was added to a stirring solution of DIEA (646 μL, 3.70 mmol), HATU (563 mg, 1.48 mmol), 5-(benzyloxy)-2-(4-fluorophenyl)furo[2,3-c]pyridine-3-carboxylic acid (448 mg, 1.23 mmol) in DMF (12 mL) at room temperature. The mixture concentrated then 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 5-(benzyloxy)-2-(4-fluorophenyl)-N-methylfuro[2,3-c]pyridine-3-carboxamide (180 mg, 39% yield) consistent by LCMS and NMR. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.62 (1H, s), 8.37-8.45 (1 H, m), 7.98-8.08 (2H, m), 7.29-7.50 (7H, m), 7.06 (1H, s), 5.42 (2H, s), 2.83 (3 H, d, J=4.52 Hz). LC-MS retention time: 2.00 min; m/z (MH+): 377. 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.

1. concentrationThe mixture concentrated
2. additionthen diluted with EtOAc
3. washwashed
4. dry with materialThe organic phase was dried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated
7. customwas purified on silica gel (Biotage, EtOAc/hexanes gradient, fraction collection at λ=254 nm)

ORD-Eintrag

ord-1d083c259b97469383468e0eb2bbe294

Quelldatensatz

uspto-grants-2013_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08536338B2