Synthesis of New Derivatives of 4‐(4,7,7‐Trimethyl‐7,8‐dihydro‐6H‐benzo[b]pyrimido[5,4‐e][1,4]thiazin‐2‐yl)morpholine

Abstract

Cyclocondensation of 5‐amino‐6‐methyl‐2‐morpholinopyrimidine‐4‐thiol (1) and 2‐bromo‐5,5‐dimethylcyclohexane‐1,3‐dione (2) under mild reaction condition afforded 4,7,7‐trimethyl‐2‐morpholino‐7,8‐dihydro‐5H‐benzo[b]pyrimido[5,4‐e][1,4]thiazin‐9(6H)‐one (3). The 1H and 13C NMR data of compound (3) are demonstrated that this compound exists primarily in the enamino ketone form. Reaction of compound (3) with phosphorous oxychloride gave 4‐(9‐chloro‐4,7,7‐trimethyl‐7,8‐dihydro‐6H‐benzo[b]pyrimido[5,4‐e][1,4]thiazin‐2‐yl)morpholine (4). Nucleophilic substitution of chlorine atom of compound (4) with typical secondary amines in DMF and K2CO3 furnished the new substituted derivatives of 4‐(4,7,7‐trimethyl‐7,8‐dihydro‐6H‐benzo[b]pyrimido[5,4‐e][1,4]thiazin‐2‐yl)morpholine (5a, 5b, 5c, 5d, 5e, 5f, 5g, 5h). All the synthesized products were characterized and confirmed by their spectroscopic and microanalytical data.

Synthesis of New Pyrimido[5′,4′:5,6][1,4]thiazino[2,3‐b]quinoxaline Derivatives in One Step

“…Based on the mentioned facts and also in continuation of our previous studies in the synthesis of new heterocyclic compounds , the present study reports the synthesis of new derivatives of pyrimido[5′,4′:5,6][1,4]thiazino[2,3‐ b ]quinoxaline through the one‐pot heterocyclization of the appropriate 5‐amino6‐methylpyrimidine‐4‐thiols and 2,3‐dichloroquinoxaline. N ‐alkylation of the synthesized compounds with several alkyl halides also gave the desired new derivatives of N ‐alkylated pyrimido[5′,4′:5,6][1,4]thiazino[2,3‐ b ]quinoxalines ( 4a–h ).…”

“…Our previous published studies on the synthesis and using of 5‐amino6‐methylpyrimidine‐4‐thiols ( 1 ) in heterocyclization reactions prompted us to explore another aspects of treatment with the 2,3‐dichloroquinoxaline ( 2 ) thereby leading to the corresponding fused pyrimido[5′,4′:5,6] [1,4] thiazino[2,3‐ b ]quinoxaline ( 3a–d ) derivatives in the presence of K 2 CO 3 in dimethylformamide (DMF) under reflux. The heterocyclization occurred in one step and any intermediate was not isolated.…”

“…On the other hand, fused heterocyclic compounds containing pyrimidothiazine as central core in particular have been studied recently and found to possess wide biological properties, like antibacterial , antiparkinsonism , anti‐allergic , and 15‐Lipoxygenase inhibition . Commonly major methods for preparation of fused heterocyclic pyrimidothiazines have also been mentioned in the literature .…”

Synthesis of new derivatives of 4-(4-methyl-5H-pyrimido[4,5-b][1,4]thiazin-2-yl)morpholine and 4-methyl-2-(piperidin-1-yl)-5H-pyrimido[4,5-b][1,4]thiazine

“…20,21 Commonly employed methods for the synthesis of fused-ring pyrimidothiazines have also been reported in the literature. 21,[22][23][24][25][26][27][28] In view of the aforementioned facts and also in continuation of our research program on the synthesis of new heterocyclic compounds, 21,22,29,30 we now report the synthesis of new derivatives of 4-(4-methyl-5H-pyrimido [4,5-b][1,4]thiazin-2-yl)morpholine and 4-methyl-2-(piperidin-1-yl)-5H-pyrimido [4,5-b][1,4]thiazine. All the synthesised products were characterised and confirmed by their spectroscopic and microanalytical data.…”