Synthesis of 4-(Dimethylamino)quinazoline via Direct Amination of Quinazolin-4(3H)-one Using N,N-Dimethylformamide as a Nitrogen Source at Room Temperature

Abstract

1) TsCl, Na 2 CO 3 THF 2) DMF, KOt-Bu r.t., 1 h 60-89% R 1 = aryl, heteroaryl R 2 = Me, Br Abstract An efficient direct amination of quinazolin-4(3H)-ones using N,N-dimethylformamide as a nitrogen source is described that affords the corresponding 4-(dimethylamino)quinazolines in high yields. This transformation proceeds through efficient 4-toluenesulfonyl chloride mediated C-OH bond activation at room temperature.

Rhodium-catalyzed C–H selective amination of 2,4-diarylquinazolines with N-fluorobenzenesulfonimide

“…Yellow solid, 90% yield, mp = 176-180°C; 1 H NMR (400 MHz, CDCl 3 ) δ 8.07 (d, J = 9.2 Hz, 1H), 7.85 (d, J = 7.5 Hz, 4H), 7.72 (s, 1H), 7.64 (d, J = 7.6 Hz, 1H), 7.57 (dd, J = 9.2, 2. 7 Hz,1H),6H),7.23 (dd,J = 14.8,6.8 Hz,5H),6.82 (d, J = 7.9 Hz, 1H), 3.89 (s, 3H), 2.46 (s, 3H), 2.30 (s, 3H); 13 C NMR (100 MHz, CDCl 3 ) δ 166. 4, 158.6, 157.9, 147.2, 141.1, 140.1, 139.4, 138.5, 137.3, 133.3, 133.1, 133.0, 130.9, 130.8, 130.5, 129.5, 129.3, 128.4, 128.2, 127.1, 126.0, 122.1, 104.4, 55.7, 21.5, 21. 8.19 (d,J = 8.6 Hz,1H),7.90 (t,J = 6.7 Hz,4H),7.85 (dd,J = 7.8,6.4 Hz,7H),7.57 (t,J = 7.6 Hz,1H),7.45 (d,J = 7.4 Hz,1H),7.28 (d,J = 7.4 Hz, 1H), 7.17 (t, J = 7.7 Hz, 4H), 7.07 (s, 1H), 2.43 (s, 3H); 13 C NMR (100 MHz, CDCl 3 ) δ 165.…”

“…5 Recently, N-fluorobenzenesulfonimide (NFSI) as a nitrogen source to realize the 4-amination reaction of quinazolinones under mild conditions was developed by Peng's group. 6 In 2015, a rhodium-catalyzed direct amination of arene C-H bonds using azides as the nitrogen source was developed by Chang and co-workers. 7 Subsequently, Peng's group developed an efficient rhodium-catalyzed C-H bond-activated amination reaction of azides with 2,4-diarylquinazolines.…”

N,N-Dialkyl Amides as Versatile Synthons for Synthesis of Heterocycles and Acyclic Systems

“…KO t Bu was used as base which leads to the formation of tosylate which attacks DMF which in turn undergoes hydrolysis to give aminated product 59. This reaction is inexpensive and uses easy to handle reagents [59].…”