Diisopropylethylamine → HCID 78162456, compound

Participants

Reaction Steps

Benzotriazol-1-yloxytripyrrolidinophosphonium hexafluorophosphate (AK Scientific, Inc., Union City, Calif.) (226 mg, 0.43 mmol) was added to a solution of 2-(1-aminoethyl)-5-(3-((1-hydroxy-2-methylpropan-2-yl)amino)-2-methylquinoxalin-5-yl)-1H-pyrrole-3-carboxylic acid hydrochloride (302d) (140 mg, 0.33 mmol) and DIPEA (0.23 mL, 1.33 mmol) in CH2Cl2 (8 mL) and DMF (8 mL) at RT. After 30 min the reaction mixture was concentrated. The residue was put into solution with EtOAc and the organic layer was washed with water, saturated NaHCO3 (aq.) and brine. The organic layer was dried over anhydrous Na2SO4, filtered and concentrated. The crude material was absorbed onto a plug of silica gel and purified by silica gel chromatography (0-5% MeOH in CH2Cl2) to provide 2-(3-((1-hydroxy-2-methylpropan-2-yl)amino)-2-methylquinoxalin-5-yl)-6-methyl-5,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-one (302e) (35 mg, 0.096 mmol, 28% yield) as a yellow foam. The mixture of enantiomers was separated by chiral SFC (Chiralcel OJ (Sepax) (21×250, 5 μm); additive in supercritical fluid CO2 was 15% MeOH with 20 mM NH3; 75 mL/min; column temperature 40° C.; outlet pressure 100 bar) to give Example 302: (R)-2-(34(1-hydroxy-2-methylpropan-2-yl)amino)-2-methylquinoxalin-5-yl)-6-methyl-5,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-one (22 mg, 0.06 mmol, 18% yield, >99% ee). 1H NMR (400 MHz, CDCl3) δ ppm 7.92 (dd, J=7.63, 1.56 Hz, 1H), 7.69 (dd, J=8.02, 1.56 Hz, 1H), 7.39 (t, J=7.82 Hz, 1H), 6.87 (d, J=1.56 Hz, 1H), 4.60-4.69 (m, 1H), 3.80-3.91 (m, 2H), 2.59 (s, 3H), 1.63-1.64 (m, 3H), 1.61-1.62 (m, 3H), 1.53 (d, J=6.65 Hz, 3H). m/z (ESI, +ve) 366.2 (M+H)+.

Provenance & Evidence