Water → HCID 58529330, compound

Participants

Reaction Conditions

Reaction Steps

To a stirred suspension of Intermediate C (2.62 g mg, 7.85 mmol) and tert-butyl 3-(4-amino-5-bromopyrrolo[2,1-f][1,2,4]triazin-7-yl)pyrrolidine-1-carboxylate (2.50 g, 6.54 mmol) in degassed DMF (6.7 mL) was added solid potassium phosphate (4.16 g, 19.62 mmol) followed by water (833 uL, 49 mmol). The reaction mixture was taken through three purge-fill cycles using nitrogen and vacuum. The reaction was then heated (100° C.) for 1 h and then cooled to rt. The mixture was partitioned between ethyl acetate (200 mL) and H2O (100 mL). The layers were separated and the organic layer was washed 6 times with brine to remove DMF (50 mL each), dried (Na2SO4), and concentrated to dryness. The crude residue was purified by ISCO® chromatography using a gradient of 50 to 100% ethyl acetate in dichloromethane to afford 1.27 g (38%) of the desired product as an off-white solid. 1H NMR (300 MHz, DMSO-d6) δ 8.53 (s, 1 H), 7.93 (s, 1 H), 7.80 (d, 1 H), 7.59 (s, 1 H), 7.35-7.30 (m, 4H), 7.15 (d, 1 H), 6.66 (s, 1H), 5.64 (s, 2 H), 3.9-3.7 (m, 1 H), 3.50-3.30 (m, 4H), 2.42 (m, 1H), 2.13 (m, 1H), 1.38 (s, 9H); ES-MS m/z 510.3 [M+H]+, HPLC RT (min) 3.16.

Provenance & Evidence