Potassium Hydroxide → HCID 66823658, compound

Participants

Reaction Conditions

Reaction Steps

To a stirred mixture of 2,2-diethoxy-N,N-dimethylethanamine (15.7 g, 97.5 mmol) and water (16.4 mL) at room temperature under a nitrogen atmosphere was added aq. 37% HCl (16.4 mL, 195 mmol). After addition the mixture was stirred at 40° C. (bath) for 25 hours. It was then cooled to 0° C. (bath) to give Solution A. KOH (14.0 g, 250 mmol) was dissolved in water (75 mL) at room temperature under a nitrogen atmosphere. It was then cooled to 0° C. (bath) to give Solution B. To a stirred heterogeneous mixture of compound 160 (19.97 g, 39.0 mmol) at room temperature under a nitrogen atmosphere was added a minimum amount of DMA (60 mL) to give a homogeneous solution. LiCl (1.65 g, 39.0 mmol) was then added and the resulting mixture was stirred at 0° C. (bath) for 15 min. The cold Solution B was then added and the reaction was stirred at 0° C. for 2 min. Cold Solution A was then added and the final reaction mixture was stirred further at 0° C. under a nitrogen atmosphere. The reaction was monitored by TLC (DCM/MeOH=10:1). After 30 min more KOH (s) (5.0 g, 89 mmol) was added and the reaction was stirred further at 0° C. for 1.5 hours. It was then poured into water (1,000 mL). Petroleum ether (1,000 mL) was added and the mixture was stirred at room temperature for 20 min. The petroleum ether layer was decanted before more petroleum ether (600 mL) was added and the mixture was again stirred for 15 min. The solid was collected by filtration, washed with water (5×200 mL) and dried under reduced pressure over silica gel/KOH to give (2E)-N-[4-(3-bromo-4-fluoroanilino)pyrido[3,4-d]pyrimidin-6-yl]-4-(dimethylamino)-2-butenamide (161) (16.9 g, 97%).

Provenance & Evidence