Trifluoroacetic acid → N4-(3-chloro-4-(3-chlorobenzyloxy)phenyl)pyrido[3,4-d]pyrimidine-4,6-diamine

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Reaction Steps

To a stirred heterogeneous mixture of compound 210 (1.46 g, 2.74 mmol) and dry DCM (27 mL) was added trifluoroacetic acid (2.1 mL, 27.4 mmol), followed by anisole (0.60 mL, 5.48 mmol), and the mixture was stirred further at room temperature for 91 h. It was poured into petroleum ether (300 mL) and stirred at room temperature for ca. 30 min. Petroleum ether layer was decanted and discarded. The process was repeated with more petroleum ether (300 mL). The residue left behind was dissolved in mixed solvents of acetone-water=1:1 (ca. 100 mL) and stirred with 5M NH3 (100 mL) at room temperature for 1 h. The solid was filtered and washed successively with acetone-water=1:4 (5×20 mL), petroleum ether-ethyl acetate=3:1 (5×20 mL), and dried to give N4-(3-chloro-4-(3-chlorobenzyloxy)phenyl)pyrido[3,4-d]pyrimidine-4,6-diamine (219) (1.10 g, 97%), mp 251-254° C. (decomp); 1H NMR δ [(CD3)2SO] 9.70 (s, 1H), 8.68 (s, 1H), 8.34 (s, 1H), 8.04 (br s, 1H), 7.73 (br d, J=8.0 Hz, 1H), 7.57-7.53 (m, 1H), 7.48-7.39 (m, 3H), 7.26 (d, J=9.0 Hz, 1H), 7.12 (br s, 1H), 7.65 (br s, 2H), 5.24 (s, 2H). Anal. Calcd for C20H13Cl2N5O: C, 58.27; H, 3.67; N, 16.99. Found C, 58.33; H, 3.57; N, 17.2.

Provenance & Evidence