Trifluoroacetic acid → N4-(3-chloro-4-(pyridin-2-ylmethoxy)phenyl)pyrido[3,4-d]-pyrimidine-4,6-diamine

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]([NH:16][C:17]2[C:18]3[CH:26]=[C:25]([NH:27]CC4C=CC(OC)=CC=4)[N:24]=[CH:23][C:19]=3[N:20]=[CH:21][N:22]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=1.FC(F)(F)C(O)=O.C1(OC)C=CC=CC=1>>[Cl:1][C:2]1[CH:3]=[C:4]([NH:16][C:17]2[C:18]3[CH:26]=[C:25]([NH2:27])[N:24]=[CH:23][C:19]=3[N:20]=[CH:21][N:22]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=1

Participants

Reactant 3

HCID 6422Trifluoroacetic acid2×

HCID 7519Anisole

HCID 86668931N4-(3-chloro-4-(pyridin-2-ylmethoxy)phenyl)-N6-(4-methoxybenzyl)pyrido[3,4-d]pyrimidine-4,6-diamine

Product 1

HCID 86668932N4-(3-chloro-4-(pyridin-2-ylmethoxy)phenyl)pyrido[3,4-d]-pyrimidine-4,6-diamineYield 89%

Procedure

To a stirred heterogeneous mixture of compound 212 (2.88 g, 5.77 mmol) and DCVI (60 ml) was added trifluoroacetic acid (4.38 ml, 57.7 mmol), followed by anisole (1.27 ml, 11.5 mmol), and the mixture was stirred further at room temperature. After 72 h another batch of trifluoroacetic acid (4.38 ml, 57.7 mmol) was added and stirred further for 49 h. It was poured into petroleum ether (250 ml) and stirred at room temperature for ca. 20 min. Petroleum ether layer was decanted and discarded. The process was repeated with more petroleum ether (250 ml). The solid left behind was dissolved in acetone (150 mL) and 5M NH3 (125 ml) added at 0° C. The mixture was stirred at room temperature for 30 min. The solid was collected and washed successively with acetone/water (1:4) (5×30 ml), petroleum ether/ethyl acetate=3:1 (5×30 ml), and dried to give N4-(3-chloro-4-(pyridin-2-ylmethoxy)phenyl)pyrido[3,4-d]-pyrimidine-4,6-diamine (221) (1.94 g, 89%), mp 247-250° C.; 1H NMR. δ [(CD3)2SO] 9.64 (s, 1H), 8.68 (s, 1H), 8.62-8.56 (m, 1H), 8.33 (s, 1H), 8.06 (d, J=2.6 Hz, 1H), 7.88 (td, J=7.7, 1.8 Hz, 1H), 7.73 (dd, J=9.0, 2.6 Hz, 1H), 7.58 (br d, J=7.8 Hz, 1H), 7.40-7.34 (m, 1H), 7.26 (d, J=9.0 Hz, 1H), 7.12 (s, 1H), 6.23 (s, 2H), 5.29 (s, 2H). Anal. Calcd for C19H13ClN6O.1.5H2O: C, 56.23; H, 4.47; N, 20.71%. Found C, 56.55; H, 4.45; N, 20.42%.