Benzyl Chloride → (1-Benzyl-1H-indazol-5-yl)-[5-(2-methoxy-ethoxymethyl)-pyrrolo[2,1-f][1,2,4]triazin-4-yl]-amine

Participants

Reaction Steps

A suspension of 5-bromomethyl-4-chloro-pyrrolo[2,1-f][1,2,4]triazine (50 mg, 0.202 mmole and NaHCO3 (75 mg, 4.4 equiv) in 2-methoxyethanol (1.0 mL) under N2 was left stirring at RT for 6 hr. The reaction was diluted with DCM, extracted with water and dried (Na2SO4). Removal of the solvent left 4-chloro-5-(2-methoxy-ethoxymethyl)-pyrrolo[2,1-f][1,2,4]triazine (41 mg, 84%) as an oil. 1H NMR (CDCl3) δ 3.40 (s, 3H), 3.67 (m, 4H), 4.96 (s, 2H), 7.05 (d, 1H, J=3 Hz), 7.82 (d, 1H, J=1 Hz), 8.16 (s, 1H). A suspension of 4-chloro-5-(2-methoxy-ethoxymethyl)-pyrrolo[2,1-f][1,2,4]triazine (5 mg, 0.020 mmole), NaHCO3 (3 mg, 2 equiv) and 1-benzyl-1H-indazol-5-ylamine (4.5 mg, 1 equiv, prepared in the same manner as 1-(3-fluoro-benzyl)-1H-indazol-5-ylamine but using benzyl chloride) in dry CH3CN (0.5 mL) was left stirring at RT for 2 hr. The reaction was diluted with DCM, washed with water and dried (Na2SO4). Removal of the solvent followed by radial chromatography (1 mm silica gel plate, gradient elution with DCM containing 0 to 1% MeOH) afforded the product as and oil (1.8 mg, 21%). 1H NMR (CDCl3) δ 3.16 (s, 3H), 3.63 (m, 4H), 4.83 (s, 2H), 5.53 (s, 2H), 6.48 (d, 1H, J=3 Hz), 7.1-7.5 (m, 8H), 7.88 s, 1H), 7.96 (s, 1H), 8.11 (s, 1H), 9.56 (s, 1H); MS: 429 (M+H)+; HPLC Ret Time: 2.58 min (YMC C18 S5, 4.6×50 mm, 3 min gradient (starting with 0% solvent B and ending with 70% solvent B), 4 mL/min.

Provenance & Evidence