4-Aminotetrahydropyran → HCID 56598278, compound

Participants

Reaction Steps

In a 25 mL sealable tube under nitrogen were combined 6-chloro-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-(1-methylethyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxamide (60 mg, 0.16 mmol) and tetrahydro-2H-pyran-4-amine (2 ml, 19 mmol) in EtOH (3 mL). The vessel was sealed and the reaction mixture was irradiated (microwave) at 125° C. for 2 hr. and then at 170° C. for 1 hr. The mixture was concentrated to ca. 20% volume and NMP (2 mL) added to the reaction mixture. The contents were again irradiated (microwave) first at 180° C. for 2.5 h and then at 190° C. for 75 min. The mixture was evaporated under vacuum, and the resulting residue was purified by silica gel chromatography (eluent: gradient 0 to 90:10:1 DCM/MeOH/NH4OH). The isolated product was treated with EtOAc/hexanes (1:1), sonicated, and heated. After cooling, solids that precipitated were filtered and dried to afford the title compound (46 mg, 64%) as an off-white solid. LCMS E-S (M+H)=439.1. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.55 (s, 1H) 8.44 (t, J=5.05 Hz, 1H) 7.83 (s, 1H) 7.20 (d, J=7.33 Hz, 1H) 6.63 (s, 1H) 5.89 (s, 1H) 4.93 (quin, J=6.69 Hz, 1H) 4.32 (d, J=5.05 Hz, 2H) 3.99-4.06 (m, 1H) 3.88 (dt, J=11.49, 3.47 Hz, 2H) 3.45 (td, J=11.37, 2.02 Hz, 2H) 2.21 (s, 3H) 2.13 (s, 3H) 1.95 (d, J=10.61 Hz, 2H) 1.41-1.51 (m, 8H).

Provenance & Evidence