Ethyl Acetate → HCID 71133987, compound

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of N-t-BOC-sarcosine (44.0 mg, 0.233 mmol, 1.2 eq), ByPOP (120 mg, 0.27 mmol, 1.4 eq), and diisopropylethylamine (0.10 mL, 0.58 mmol, 3.0 eq) in anhydrous THF (1.9 mL) and DCE (1.0 mL) was added 5-(3-amino-2-benzyl-2H-indazol-6-yl)-7-piperidin-4-yl-pyrrolo[2,1-f][1,2,4]triazin-4-ylamine (85 mg, 0.194 mmol). The reaction mixture was stirred at 40° C. under N2 for 18 h and cooled to rt. The mixture was cooled and poured into EtOAc. The organic phase was washed with water and brine, dried over Na2SO4, filtered, and concentrated in vacuo. The residue was dissolved in anhydrous THF (2.0 mL), and 1.0 M sodium methoxide in MeOH (0.5 mL) was added. The reaction mixture was stirred at it for 18 h and poured into EtOAc. The organic layer was washed with water and brine, dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified using an ISCO® instrument (gradient 0 to 25% MeOH/EtOAc) and the product containing fractions were concentrated. Trituration with DCM-hexane afforded 43.9 mg (37.2%) of the title compound as pink solid. 1H NMR (300 MHz, DMSO-d6) δ 7.89 (s, 1H), 7.71 (d, 1H), 7.34 to 7.29 (m, 2H), 7.27 to 7.14 (m, 3H), 7.15 (t, 1H), 6.73 (t, 1H), 6.56 (s, 0.5H), 6.48 (s, 0.5H), 6.37 (s, 2H), 5.38 (s, 2H), 4.50 to 4.45 (m, 1H), 4.13 to 3.83 (m, 3H), 3.44 to 3.35 (m, 1H), 3.16 (t, 1H), 2.78 to 2.70 (m, 4H), 2.07 to 2.04 (m, 2H), 1.66 to 1.51 (m, 2H), 1.35 (d, 9H); ES-MS m/z 610.0 [M+H]+, RT (min) 2.55.

Provenance & Evidence