Dimethylamine → HCID 86663610, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of DCC (7.23 g, 35.1 mmol) in dry THF (25 ml) at 0° C. under nitrogen, was added solid acid 9 (5.79 g, 35.1 mmol). The reaction mixture was stirred at 0° C. for 35 min before solid aniline 169 (1.83 g, 7.01 mmol) was added, followed by dry DMA (20 mL) and di-iso-propylethylamine (DIPEA) (6.11 ml, 35.1 mmol). The final reaction mixture was stirred at 0° C. for 45 min before being cooled to −15 to −20° C. (bath). 40% Aqueous dimethylamine (10.6 mL, 84.0 mmol) was then added and after 25 min the reaction mixture was poured into cold 2% aqueous sodium carbonate (200 mL) and the product was extracted into ethyl acetate (600 mL), which was washed successively with water (300 mL), cold 2% aqueous sodium carbonate (300 mL) and water (300 mL). The ethyl acetate solution was dried (Na2SO4) and evaporated under reduced pressure to give a solid which was purified by column chromatography on silica gel eluting with DCM/MeOH (gradient from 100:0 to 15:1), to give (2E)-4-(dimethylamino)-N-[4-(3-ethynylanilino)pyrido[3,4-d]pyrimidin-6-yl]-2-butenamide (171) (1.33 g, 51%) as a yellow/orange solid, mp 163-166° C. 1H NMR δ [(CD3)2SO] 10.89 (s, 1H), 10.25 (s, 1H), 9.02 (s, 1H), 9.00 (s, 1H), 8.63 (s, 1H), 8.02 (br s, 1H), 7.94-7.87 (m, 1H), 7.42 (t, J=7.9 Hz, 1H), 7.26 (br d, J=7.7 Hz, 1H), 6.88 (dt, J=15.4, 6.0 Hz, 1H), 6.52 (br d; J=15.4 Hz, 1H), 4.19 (s, 1H), 3.09 (dd, J=6.0, 1.2 Hz, 2H), 2.19 (s, 6H). Anal. Calcd for C21H20N6O.0.2H2O: C, 67.08; H, 5.47; N, 22.35%. Found C, 66.88; H, 5.47; N, 22.22%.

Provenance & Evidence