1,4-Dioxane → HCID 178420026, compound

Participants

Reaction Conditions

Reaction Steps

Cyclopropyl(2-fluoropyridin-3-yl)methanone (intermediate 53, 0.270 g, 1.635 mmol), N-(trans-3-hydrazinylcyclobutyl)benzo[d]thiazol-2-amine dihydrochloride (intermediate 52, 0.502 g, 1.635 mmol), and potassium acetate (0.462 ml, 7.39 mmol) were suspended in a mixture of dry dioxane (5 mL), dry ethanol (5 mL), and dry toluene (5 mL) and heated at 105° C. for 30 minutes. The temperature was lowered to 90° C. and additional potassium acetate (1.2 g, 6.6 eq) was added. The mixture was stirred for another 90 minutes. After another 3 hours the reaction was evaporated to dryness under reduced pressure. Purification using silica chromatography (0-10% (2 N ammonia in methanol) in dichloromethane gradient) followed by repurification using reverse phase HPLC and free basing (ethyl acetate/saturated sodium bicarbonate) gave the desired N-(trans-3-(3-cyclopropyl-1H-pyrazolo[3,4-b]pyridin-1-yl)cyclobutyl)benzo[d]thiazol-2-amine (0.170 g, 0.470 mmol, 28.8% yield) as a white solid. M+1: 362.1. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 0.87-1.20 (m, 4 H) 2.12-2.22 (m, 1 H) 2.49-2.71 (m, 2 H) 3.00-3.26 (m, 2 H) 4.36-4.58 (m, 1 H) 5.63 (quin, J=7.24 Hz, 1 H) 6.61 (br. s., 1 H) 6.89-7.12 (m, 2 H) 7.21 (br. s., 1 H) 7.53 (m, J=7.80 Hz, 2 H) 7.94 (dd, J=7.82, 1.17 Hz, 1 H) 8.39 (dd, J=4.40, 1.08 Hz, 1 H).

Provenance & Evidence