1-Hydroxybenzotriazole → 2'-(3-(tert-butylamino)-6-fluoro-2-methylquinoxalin-5-yl)-1'H-spiro[cyclopropane-1,6'-pyrrolo[3,4-b]pyrrol]-4'(5'H)-one

Participants

Reaction Steps

To a suspension of 2-(1-aminocyclopropyl)-5-(3-(tert-butylamino)-6-fluoro-2-methylquinoxalin-5-yl)-1H-pyrrole-3-carboxylic acid hydrochloride (295c) (140 mg, 0.32 mmol) in 8 mL of DMF and 8 mL of DCM at RT was sequentially added 1-hydroxybenzotriazole (AK Scientific, Inc., Union City, Calif.) (65 mg, 0.48 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (Sigma-Aldrich) (93 mg, 0.48 mmol) and DIPEA (Sigma-Aldrich) (0.34 mL, 1.94 mmol). The reaction mixture was stirred at RT for 16 h and was then concentrated. The yellow oil was dissolved in CH2Cl2 and washed with water, 1 M NaOH (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-(tert-butylamino)-6-fluoro-2-methylquinoxalin-5-yl)-1′H-spiro[cyclopropane-1,6′-pyrrolo[3,4-b]pyrrol]-4′(5′H)-one (295) (50 mg, 0.13 mmol, 41% yield) as a light yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.52 (s, 1H), 7.70 (dd, J=9.00, 5.87 Hz, 1H), 7.63 (s, 1H), 7.30 (dd, J=10.47, 8.90 Hz, 1H), 6.49-6.55 (m, 1H), 6.07 (s, 1H), 2.54 (s, 3H), 1.43 (s, 9H), 1.37-1.41 (m, 2H), 1.29-1.35 (m, 2H). 19F NMR (376 MHz, DMSO-d6) δ ppm −111.61 (s, 1F). m/z (ESI, +ve) 380.1 (M+H)+.

Provenance & Evidence