Water → 4-[2-(4-Morpholin-4-yl-phenylamino)-pyrrolo[2,1-f][1,2,4]triazin-7-yl]-piperidine-1-carboxylic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

Into a 30 mL vial, Palladium Acetate (35 mg, 0.16 mmol) and Triphenylphosphine (100 mg, 0.4 mmol) were added and purged under an atmosphere of Nitrogen for 10 minutes. 1,4-Dioxane (5.9 mL) was added and stirred for 10 minutes. (7-Bromo-pyrrolo[2,1-f][1,2,4]triazin-2-yl)-(4-morpholin-4-yl-phenyl)-amine (0.250 g, 0.668 mmol), 4-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (0.413 g, 1.34 mmol), N,N-Dimethylformamide (5.9 mL) and 1.50 M of Sodium carbonate in Water (2.47 mL, 3.70 mmol) were added and heated at 85° C. for 8 hours. The reaction was partitioned with DCM. The solid was filtered and washed with DCM. The organic solvent was removed under vacuum. The desired product was isolated via ISCO column chromatography with DCM and methanol as eluant (0 to 10% methanol). The collected fractions afforded 4-[2-(4-Morpholin-4-yl-phenylamino)-pyrrolo[2,1-f][1,2,4]triazin-7-yl]-piperidine-1-carboxylic acid tert-butyl ester as a yellow solid (180, 56%). LCMS (E/I+) 477.8 (M+H). NMR 1H (DMSO-d6)-9.15 (s, 1H), 8.88 (s, 1H), 7.57 (d, 2H, J=8.75 Hz), 7.10 (bs, 1H), 6.91 (d, 2H, J=8.75 Hz), 6.82 (d, 1H, J=4.66 Hz), 6.79 (d, 1H, J=4.66 Hz), 4.12 (bs, 2H), 3.74 (t, 4H, J=4.66 Hz), 3.58 (t, 2H, J=5.25 Hz), 3.06 (t, 4H, J=5.25 Hz), 2.58 (bs, 2H), 1.44 (s, 9H).

Provenance & Evidence