Untersuchungen an 1,3‐Dicarbonyl‐Verbindungen, 18. Mitt. 2,4‐Diaryl‐6‐methyl‐1,2,3,4‐tetrahydropyrimidin‐5‐carbon‐säureester

Abstract

Bei der Hanrzsch-Synthese werden neben den 1,4-Dihydropyridinen 1 die diastereomeren 1,2,3,4-Tetrahydropyrimidine 2 und 3 erhalten. Die Titelverbindungen werden zu den Pynmidinen 7 oxidiert. Photolyse von Id liefert das Dimer 10. k, M und k, 3d werden photochemisch zu den Bisnitrosophenylpyrimidinen 11 umgesetzt. Unter reduktiven Bedingungen werden aus k die Abbauprodukte 12 und l3 isoliert.In addition to the 1,4-dihydropyridines 1, the diastereomeric 1,2,3,4-tetrahydropyrimidines 2 and 3 are obtained by Hanfzsch synthesis. The title compounds are oxidized to yield the pyrimidines 7. The dimer 10 is formed on photolysis of Id. Compounds k, M and k, 3d are converted by irradiation to the bis(nitrosopheny1)pyrimidines 11. Under reductive conditions the degradation products U and W are isolated. 1887 studierte Lepetit) aus dem Laboratorium von Hanfzsch ,,das Verhalten der drei Nitrobenzaldehyde gegen Acetessigather und Ammoniak". Leperit stellte fest, daR nur mit 2-Nitrobenzaldehyd zwei Substanzen entstehen, und zwar beide in bemerkenswert besserer Ausbeute, wenn man aquimolare Mengen von Acetessigstiureethylester und 2-Nitrobenzaldehyd mit iiberschussigem Ammoniak reagieren labt. Fur die zuerst aus dem Reaktionsansatz kristallisierende Verbindung wurden aufgrund der Analyse die Summenformeln C19HmN405 oder CI9HzN4O5 diskutiert und die wassentoffirmere Formel fur wahrscheinlicher gehalten. Aus der Mutterlauge wurde das normale Hanrzsch-Produkt, 3,5-Diethoxycarbonyl-2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridin (ld), isoliert. Wir interessierten uns fiir diese Arbeit, wed der korrespondierende Dimethylester lc, Nifedipin (Adalat8)4J), 1975 als Calciumantagonist zur Therapie koronarer Herzkrankheiten eingefiihrt wurde.Beim Nacharbeiten der von Leperit) angegebenen Vorschrift konnten wir jedoch durch fraktionierte Kristallisation drei Substanzen isolieren. Zunachst kristallisierten zwei Isomere der Summenformel &H2,$J4O6, danach Id. Demnach haben einerseits nvei + vorgetragen anliRlich der Tagung der Deutschen Pharmazeutischen Gesellschaft, Regensburg, 25. 9. 1980.

Palladium(II) Catalyzed Suzuki/Sonogashira Cross‐Coupling Reactions of Sulfonates: An Efficient Approach to C2‐Functionalized Pyrimidines and Pyridines

“…Ethyl 4-Methyl-2,6-diphenylpyrimidine-5-carboxylate (3a): [23] White solid; m.p. and PPh 3 (52.5 mg, 0.20 equiv.)…”

“…To our delight, the C-C cross-coupling product 3a was isolated in 80 % yield (entry 5). We also examined several pyridin-2-yl sulfonates, including pyridin-2-yl sulfonate (1g), and 5-bromo-, 5-methyl-and 5-nitro substituted pyridin-2-yl sulfonates (1h-j) as substrates in the Suzuki-Miyaura coupling reaction with four arylboronic acids ( Table 2, entries [17][18][19][20][21][22][23][24][25][26]. This revealed that the reaction was best conducted with 5 mol-% Pd(OAc) 2 as the catalyst and either 20 mol-% PPh 3 or 6 mol-% 2,2Ј-oxybis(2,1-phenylene)bis(diphenylphos-phane) (DPE-Phos) as ligand, and 2.5 equivalents of K 3 PO 4 as base, 1,4-dioxane as solvent at 110°C for 7 h, which afforded the desired product in an isolated yield of 86 or 87 %, respectively (entries 4-9).…”

“…Lower yield of 3a was obtained when tetrahydrofuran (THF) was used as solvent (entries 1-3). The reactions of pyridin-2-yl sulfonates with arylboronic acids proceeded smoothly, giving the products 3q-z in moderate to good yields (entries [17][18][19][20][21][22][23][24][25][26]. Under the optimized conditions, various pyrimidin-2-yl sulfonates (1) and a diverse set of arylboronic acids (2) were used to test the scope of the reaction ( Table 2).…”

“…This revealed that the reaction was best conducted with 5 mol-% Pd(OAc) 2 as the catalyst and either 20 mol-% PPh 3 or 6 mol-% 2,2Ј-oxybis(2,1-phenylene)bis(diphenylphos-phane) (DPE-Phos) as ligand, and 2.5 equivalents of K 3 PO 4 as base, 1,4-dioxane as solvent at 110°C for 7 h, which afforded the desired product in an isolated yield of 86 or 87 %, respectively (entries 4-9). Arylboronic acids with electron-rich functional groups (Me, MeO) have significantly higher activity than the unsubstituted arylboronic acids (entries [17][18][19][20][21][22][23][24][25][26]. In general, good to excellent yields (63-96 %) were obtained under the standard reaction conditions using PPh 3 as the ligand (entries 1-16).…”

On the reaction of 3,4‐dihydropyrimidones with nitric acid. Preparation and x‐ray structure analysis of a stable nitrolic acid

“…If one would assume that dinitration of DHPM 1 at 50 °C (60% HNO 3 ) leads to gemdinitro pyrimidone B/C, an internal redox process would readily furnish nitrolic acid 5. Although there is literature precedent for the gem-dinitration of active methylene and methyl groups [8,[35][36][37], we are not aware of any precedent for a (non-photochemical [38][39][40][41]) redox process such as the hypothetical C → H transformation.…”