Synthesis of 3(2)-phosphonylated thiazolo[3,2-a]oxopyrimidines

Abstract

A series of 3(2)-phosphonylated thiazolo[3,2-a]oxopyrimidines was synthesized for the first time by the reactions of chloroethynylphosphonates with unsubstituted and 5(6)-substituted 2-thiouracils. The reaction of chloroethynylphosphonates with 6-substituted 2-thiouracils bearing electron-donor groups (CH3, Ph) proceeded with high regioselectivity involving the cyclization through the N3-nitrogen atom to form new 3-phosphonylated thiazolo[3,2-a]-5-oxopyrimidines with good yield. In the case of unsubstituted and 5-methyl-2-thiouracils, cyclization occurred predominantly through the N1 atom and partially via the N3-nitrogen atom to form a mixture of the corresponding thiazolo[3,2-a]-7- and 5-oxopyrimidines. A dramatic change in the reaction regioselectivity was observed in the case of 6-trifluoromethyl-2-thiouracil that afforded 2- and 3-phosphonylated 5-oxothiazolopyrimidines in a 1:1 ratio.

Simple and Expedient Access to Novel Fluorinated Thiazolo- and Oxazolo[3,2-a]pyrimidin-7-one Derivatives and Their Functionalization via Palladium-Catalyzed Reactions

“…At room temperature and under the same conditions, the reaction proceeded with a very low yield and incomplete conversion of 1a after 72 h (Table 1, entry 12). Further optimizations were undertaken using various catalysts, including AgSO 3 CF 3 , Ag 2 CO 3 , AgOAc, Cu(OAc) 2 , Pd(Oac) 2 , ZnCl 2 , and CuBr, but did not improve the reaction yield and provided the cyclized product 3a with yields not exceeding 70% (Table 1, entries [13][14][15][16][17][18][19]. The molecular structure of the new compound 3a was unambiguously confirmed by X-ray crystal analysis, as depicted in Figure 3 [49].…”

“…Additionally, many compounds containing the oxazolo [3,2-a]pyrimidine framework are known for their pharmacological potential as anti-inflammatory [13], antihypertensive [14], and anti-leukemia agents [15]. It should be noted that some examples of structural analogues of thiazolo-and oxazolo [3,2a]pyrimidinones, are used in clinical medicine, such as Ritanserin and Setoperone, which are antipsychotics [16], and SAR218645, which is an mGluR2 positive allosteric modulator that has been shown to be effective in treating some aspects of cognitive dysfunction in schizophrenia (Figure 1) [17].…”

Metal‐Free Site‐Selective Direct Oxidative Phosphorylation of Pyrazolones

“…[11] From the synthetic point of view, direct phosphorylation reactions to introduce the phosphorus moiety to non-prefunctionalized N-heterocyclic scaffolds are very attractive and useful for a preparation of the new phosphorus-containing compounds. To the best of our knowledge, a classical preparation of phosphorylated pyrazolones involved an addition-elimination sequence and followed by the intramolecular cyclization, [12] which required an additional multi-step route for substrate preparation, leading to poor atom-and stepeconomy, and limited the structural diversity and further utilization.…”