1-Pyrrolidinepropanamine → 7-(3-{[(3-isopropylphenyl)amino]carbonyl}phenyl)-N-(3-pyrrolidin-1-ylpropyl)-5,6,7,8-tetrahydro-2,7-naphthyridine-4-carboxamide

Participants

Reaction Steps

To a mixture of 7-(3-{[(3-isopropylphenyl)amino]carbonyl}phenyl)-5,6,7,8-tetrahydro-2,7-naphthyridine-4-carboxylic acid (40 mg, 0.096 mmol), N,N-diisopropylethylamine (0.050 mL, 0.29 mmol), and catalytic DMAP in 2.5 mL 1,2-dichloroethane at rt was added propylphosphonic anhydride solution (50 wt % in EtOAc, 0.069 mL, 0.116 mmol). After 6 min at rt, 1-(3-Aminopropyl)pyrrolidine (16.0 mg, 0.125 mmol) was added and the reaction stirred at rt for 4 hours. The reaction was quenched with aqueous NaHCO3 solution, extracted with EtOAc, the EtOAc layer washed with H2O, aqueous Na2CO3 solution, brine, dried with anhydrous Na2SO4 and rotary evaporated. The sample was triturated with EtOAc, and the filtrate chromatographed eluting with CHCl3/MeOH plus triethylamine to give the title compound as a light beige solid (27 mg, 53%). 1H NMR (CDCl3) δ: 8.50 (s, 1H), 8.36-8.44 (m, 2H), 8.10 (s, 1H), 7.58 (s, 1H), 7.46-7.54 (m, 2H), 7.32-7.39 (m, 1H), 7.22-7.31 (m, 2H), 7.10 (d, J=7.6 Hz, 1H), 7.02 (d, J=7.6 Hz, 1H), 4.46 (s, 2H), 3.53-3.61 (m, 4H), 3.22 (t, J=5.4 Hz, 2H), 2.77-2.97 (m, 7H), 1.82-1.99 (m, 6H), 1.27 (d, J=6.7 Hz, 6H)

Provenance & Evidence