Diisopropylethylamine → N7-2-[di(2-hydroxyethyl)amino]ethyl-4-amino-3-(3-methoxy-4-[(1-methyl-1H-2-indolyl)carbonyl]aminophenyl)thieno[3,2-c]pyridine-7-carboxamide

A 20 mL scintillation vial was charged with 4-amino-3-(3-methoxy-4-{[(1-methyl-1H-indol-2-yl)carbonyl]amino}phenyl)thieno[3,2-c]pyridine-7-carboxylic acid (0.070 g, 0.148 mmol), O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexafluorophosphate (0.067 g, 0.177 mmol), 1-hydroxybenzotriazole hydrate (0.024 g, 0.177 mmol) and N,N-dimethylformamide (1.5 mL). To the suspension was added diisopropylethylamine (0.100 mL, 0.592 mmol) and 2-[(2-aminoethyl)(2-hydroxyethyl)amino]ethanol (0.024 mg, 0.162 mmol). The vial was flushed with nitrogen gas prior to capping, and the reaction mixture was shaken at room temperature for 12 hours. Upon completion of the reaction, methylene chloride (2 mL) and saturated sodium bicarbonate solution (2 mL) were added. The solution was filtered through an Empore™ cartridge, and the solvents removed under reduced pressure. The residues were taken up in a minimal amount of methanol and eluted (gravity) through a Si-carbonate™ cartridge (2 gram, 6 mL). The organic solution obtained was concentrated and the resulting residue triturated with water to give N7-2-[di(2-hydroxyethyl)amino]ethyl-4-amino-3-(3-methoxy-4-[(1-methyl-1H-2-indolyl)carbonyl]aminophenyl)thieno[3,2-c]pyridine-7-carboxamide as a precipitate. The title compound was collected and dried by vacuum filtration (15 mg, 14%). LCMS (Conditions a) Rt 2.62 min., 603.4 (MH+); 1H NMR (400 MHz, DMSO-d6) δ 9.51 (s, 1H), 8.51 (s, 1H), 8.39 (t, J=5.5 Hz, 1H), 7.99 (dd, J=7.8 Hz, 8.2 Hz, 1H), 7.70 (d, J=8.2 Hz, 1H), 7.59 (d, J=7.2 Hz, 1H), 7.58 (s, 1H), 7.35 (s, 1H), 7.32 (d, J=8.2 Hz, 1H), 7.20 (d, J=1.6 Hz, 1H), 7.15 (dd, J=7.8 Hz, 7.2 Hz, 1H), 7.07 (dd, J=8.2 Hz, 1.6 Hz, 1H), 4.41 (t, J=5.8 Hz, 1H), 4.04 (s, 3H), 3.91 (s, 3H), 3.44 (q, J=5.8 Hz, 4H), 3.34 (m, 2H), 2.68 (t, J=7.2 Hz, 2H), 2.61 (t, J=5.8 Hz, 4H).

1. customThe vial was flushed with nitrogen gas
2. customUpon completion of the reaction, methylene chloride (2 mL) and saturated sodium bicarbonate solution (2 mL)
3. additionwere added
4. filtrationThe solution was filtered through an Empore™ cartridge
5. customthe solvents removed under reduced pressure
6. washeluted (gravity) through a Si-carbonate™ cartridge (2 gram, 6 mL)
7. customThe organic solution obtained
8. concentrationwas concentrated
9. customthe resulting residue triturated with water

ORD record

ord-d78bf22ba79240c88ce73e2b86dba0a5

Source dataset

uspto-grants-2012_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08273736B2