58173-74-3Relevant academic research and scientific papers
Development of a Scalable Route for a Highly Polar Heterocyclic Aminocyclopropyl Building Block
Abele, Stefan,Ahmetovic, Muhamed,Fleischer, Tony,Sch?fer, Gabriel
supporting information, p. 1735 - 1742 (2020/10/26)
A robust and scalable route toward key heterocyclic building block 1-(pyrimidin-2-yl)cyclopropan-1-amine hydrochloride from cyclopropanated starting material 1-amino-1-cyclopropanecarbonitrile hydrochloride was successfully developed. The key to success was the construction of a pyrimidine ring via cyclization from an amidine intermediate and a bench-stable 2-chloro vinamidinium hexafluorophosphate salt. The cyclization was performed under mild conditions, and the resulting 4-cloropyrimidine derivative was isolated in high yield and purity. The final hydrogenation was intensively optimized: A combination of Pd(OH)2/C as a catalyst and NaOMe as a base at 1 bar H2 pressure in MeOH simultaneously cleaved the Cbz group and dechlorinated the pyrimidine ring while at the same time suppressing the over-reduction of the pyrimidine ring to below 1.0%. After acidification with HCl, followed by removal of the catalyst and NaCl by filtration, the final product was isolated in high yield and purity as a bench-stable off-white solid. The overall yield of the five-step sequence was 57%.
Inverse electron demand diels-alder reactions of 1,2,3-triazines: Pronounced substituent effects on reactivity and cycloaddition scope
Anderson, Erin D.,Boger, Dale L.
supporting information; experimental part, p. 12285 - 12292 (2011/09/16)
A systematic study of the inverse electron demand Diels-Alder reactions of 1,2,3-triazines is disclosed, including an examination of the impact of a C5 substituent. Such substituents were found to exhibit a remarkable impact on the cycloaddition reactivity of the 1,2,3-triazine without altering, and perhaps even enhancing, the intrinsic cycloaddition regioselectivity. The study revealed not only that the reactivity may be predictably modulated by a C5 substituent (R = CO2Me > Ph > H) but also that the impact is of a magnitude to convert 1,2,3-triazine (1) and its modest cycloaddition scope into a heterocyclic azadiene system with a reaction scope that portends extensive synthetic utility, expanding the range of participating dienophiles. Significantly, the studies define a now powerful additional heterocyclic azadiene, complementary to the isomeric 1,2,4-triazines and 1,3,5-triazines, capable of dependable participation in inverse electron demand Diels-Alder reactions, extending the number of complementary heterocyclic ring systems accessible with implementation of the methodology.
Scope of the inverse electron demand Diels-Alder reactions of 1,2,3-triazine
Anderson, Erin D.,Boger, Dale L.
supporting information; experimental part, p. 2492 - 2494 (2011/07/09)
Chemical equations presented. An examination of the scope of the inverse electron demand Diels-Alder reactions of the parent unsubstituted 1,2,3-triazine is described including the first report of its unique capabilities for participating in previously unexplored [4 + 2] cycloaddition reactions with heterodienophiles.
Negishi coupling of secondary alkylzinc halides with aryl bromides and chlorides
Han, Chong,Buchwald, Stephen L.
supporting information; experimental part, p. 7532 - 7533 (2009/10/16)
(Chemical Equation Presented) An efficient palladium-catalyzed process has been developed for Negishi coupling of secondary alkylzinc halides with a wide range of aryl bromides and activated aryl chlorides. A palladium catalyst composed of a new biaryldialkylphosphine ligand, CPhos, effectively promotes the rate of the reductive elimination step relative to the rate of the undesired β-hydride elimination. The broad substrate scope and excellent ratio of the desired secondary to the undesired primary coupling product make this method a powerful and reliable tool forC(sp3)-C(sp2) bond formation.
