Cyclopropylamine → HCID 178516968, compound

Participants

Reaction Steps

Trans-N1-(benzo[d]thiazol-2-yl)-N3-(3-bromopyridin-2-yl)cyclobutane-1,3-diamine (intermediate 33, 0.362 g, 0.965 mmol), sodium tert-butoxide (0.232 g, 2.411 mmol), and chloro(2-dicyclohexylphosphino-3,6-dimethoxy-2′-4′-6′-tri-1-1,1′-biphenyl)]2-(2-aminoethyl)phenyl)palladium(ii) (0.058 g, 0.072 mmol) were placed in a microwave vessel under argon. Dry, sparged dioxane (1.5 mL) was added followed by cyclopropylamine (0.170 ml, 2.424 mmol). The mixture was sealed under argon and stirred at room temperature for 15 minutes then heated in a 90° C. oil bath for 30 minutes. The reaction was cooled and opened. The reaction mixture was diluted with ethyl acetate (10 mL) and washed with water (10 mL). The organic phase was dried with magnesium sulfate and evaporated to dryness under reduced pressure. The crude was further dried under high vacuum to give a solid foam. It was dissolved in dry tetrahydrofuran (10 mL) and added to an ice cooled solution of triphosgene (0.112 g) in dry tetrahydrofuran (10 mL) and dichloromethane (10 mL). Triethylamine (6 mL) was added and the reaction stirred for 20 minutes. Water (50 mL) was added and the reaction stirred for 10 minutes. The phases were separated and the organic dried with magnesium sulfate before evaporating to dryness under reduced pressure. The crude product was purified using silica chromatography (20-100% ethyl acetate in hexane gradient) followed by reverse phase HPLC to give 3-(trans-3-(benzo[d]thiazol-2-ylamino)cyclobutyl)-1-cyclopropyl-1H-imidazo[4,5-b]pyridin-2(3H)-one (48.8 mg, 0.129 mmol, 13.40% yield). M+1: 378. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 0.95-1.07 (m, 2 H) 1.07-1.20 (m, 2 H) 2.43-2.63 (m, 2 H) 2.83-3.02 (m, 1 H) 3.45-3.66 (m, 2 H) 4.50-4.72 (m, 1 H) 5.37 (quin, J=8.36 Hz, 1 H) 6.08 (br. s., 1 H) 7.01 (dd, J=7.43, 5.48 Hz, 1 H) 7.08 (t, J=7.53 Hz, 1 H) 7.23-7.32 (m, 1 H) 7.36 (d, J=7.63 Hz, 1 H) 7.59 (dd, J=10.86, 8.31 Hz, 2 H) 8.05 (d, J=4.89 Hz, 1 H).

Provenance & Evidence