Hydrochloric Acid → HCID 86727148, compound

Participants

Reaction Conditions

Reaction Steps

In a microwave tube, a mixture of 5-bromo-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine (Intermediate 4) (100 mg, 0.300 mmol), (7-methoxyquinolin-6-yl)boronic acid (˜50% by weight, 171 mg, 0.420 mmol) and sodium carbonate (95 mg, 0.90 mmol) in 3:1 dimethoxyethane/water (2.5 mL) was degassed with a dry stream of nitrogen for five minutes. Tetrakis(triphenylphosphine)palladium(0) (34.7 mg, 0.030 mmol) was added and the mixture heated in a microwave at 140° C. for 30 min. The mixture was diluted with water and extracted with DCM (6×). HCl in dioxane (1 M, 1.2 mL, 1.2 mmol) was added and the solution concentrated to dryness. SCX purification (2 g column, 7 M ammonia in MeOH elution) provided a brown residue which was further purified by flash column chromatography (12 g silica gel, 1-17% 1.4 N ammonia in MeOH gradient in DCM over 30 column volumes) to provide 5-(7-methoxyquinolin-6-yl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine as a yellow solid (104 mg, 84%). MS=412.3 (M+1), Rt=0.45 min [Method D]. 1H NMR (400 MHz, METHANOL-d4) ppm 8.83 (dd, J=4.3, 1.8 Hz, 1H), 8.71 (s, 1H), 8.42 (d, J=8.1 Hz, 1H), 7.57 (s, 1H), 7.48 (dd, J=8.3, 4.3 Hz, 1H), 4.43-4.57 (m, 1H), 4.16 (s, 3H), 3.11 (s, 3H), 1.81 (dd, J=12.6, 3.0 Hz, 2H), 1.58 (t, J=12.4 Hz, 2H), 1.37 (s, 6H), 1.25 (s, 6H).

Provenance & Evidence