Triethylamine → HCID 44409596, compound

Participants

Reaction Steps

To a stirred solution of 4-chloro-5-methyl-pyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid methyl ester (0.5 g, 2.22 inmol) and 2-methyl-5-hydroxyindole (424 mg, 2.9 mmol) under argon in acetonitrile (10.0 mL) was added triethylamine (6.65 mmol, 0.93 mL). After stirring the mixture at room temperature for 17 h. solvent was removed under vacuum and the residue was chromatographed on silica gel eluting with 20-30% ethyl acetate (gradient) in hexanes. The solvent was removed in vacuo to obtain 5-methyl-4-(2-methyl-1H-indol-5-yloxy)-pyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid methyl ester as a white solid (0.58 g, 85%). LC/MS; (M+H)+=337.2 B. To a solution of compound A (575 mg, 1.71 mmol) in pyridine (20 mL) was added lithium iodide (17 mmol, 2.3 g). The mixture was stirred at reflux for 45 h. The mixture was allowed to cool and the pyridine was then removed in vacuo. The remaining solid material was purified by preparative HPLC. Removal of the eluent in vacuo afforded 5-methyl-4-(2-methyl-1H-indol-5-yloxy)pyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid (228 mg, 41%) as a brown solid. LC/MS; (M+H)+=323.1 C. To a solution of compound B (35 mg, 0.11 mmol) in dioxane (7 mL) was added ca. 5 mg of crushed 4 Å molecular sieves, triethylamine (0.13 mmol, 18 EL), and DPPA (0.13 mmol, 28 mL). The mixture was heated under argon at 50° C. for 6 h, followed by addition of the 3-piperidinepropanol (1.1 mmol, 156 mg) in dioxane (2.0 mL), warmed to 76° C., then allowed to stir for ca. 16 h. The reaction mixture was purified on preparative HPLC. The product obtained was then dissolved in ethyl acetate (100 mL) and washed with 30 mL of saturated aqueous sodium bicarbonate, dried, filtered and concentrated in vacuo. The oil was then chromatographed using silica gel eluting with 1% triethylamine, 10% methanol in chloroform. Removal of the solvent in vacuo afforded the title compound (9.2 mg, 18%) as an orange oil. LC/MS; (M+H)+=323.2

Provenance & Evidence