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

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.

1. stirringstirred at room temperature for ca. 30 min
2. customPetroleum ether layer was decanted
3. waitThe residue left
4. dissolutionbehind was dissolved in mixed solvents of acetone-water=1:1 (ca. 100 mL)
5. stirringstirred with 5M NH3 (100 mL) at room temperature for 1 h
6. filtrationThe solid was filtered
7. washwashed successively with acetone-water=1:4 (5×20 mL), petroleum ether-ethyl acetate=3:1 (5×20 mL)
8. customdried

ORD record

ord-a75270baaf1e4c99affa51b1aa453f6f

Source dataset

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09101632B2