911429-36-2Relevant academic research and scientific papers
Exploration of fluoral hydrazones derived from carbohydrazides for the synthesis of trifluoromethylated heterocycles
Mloston, Grzegorz,Urbaniak, Katarzyna,Jacaszek, Natalia,Linden, Anthony,Heimgartner, Heinz
, p. 387 - 401 (2014/01/17)
The reaction of fluoral hydrate with carbohydrazides in methanol in the presence of molecular sieves (4 A) gave the desired N-acylated fluoral hydrazones (3a-f) in fair yields. Treatment of the latter with mercaptoacetic acid in benzene led to the corresponding 2-trifluoromethyl-1,3-thiazolidinone derivatives (4a-f), whereas the reaction with acetic anhydride gave 3-acetyl-2,3-dihydro-2-trifluoromethyl-1,3,4-oxadiazoles (5a-f). The structures of each type of product have been established by X-ray crystallography.
New optically active bis-heterocycles derived from (S)-proline
Pieczonka, Adam M.,Mloston, Grzegorz,Linden, Anthony,Heimgartner, Heinz
, p. 1521 - 1530 (2012/11/13)
Enantiomerically pure bis-heterocycles containing a (S)-proline moiety have been prepared starting from (S)-N-benzylprolinehydrazide (2b). The reactions with isothiocyanates or butyl isocyanate in refluxing MeOH led to the corresponding thiosemicarbazide 5 and semicarbazide 9 with a N-benzylprolinoyl residue. The structure of the tert-butyl derivative 5d was established by X-ray crystallography. Base-catalyzed cyclization of 5 and 9 led to (S)-3-(pyrrolidin-2-yl)-1H-1,2,4-triazole-5(4H)-thiones 6 and the corresponding 5(4H)-one 8, respectively, whereas, in concentrated H2SO4, compounds 5 undergo cyclization to give (S)-5-amino-2-(pyrrolidin-2-yl)-1,3,4- thiadiazoles 7. Furthermore, 2b reacted with hexane-2,5-dione in boiling iPrOH to yield the (S)-N-(2,5-dimethylpyrrol-1-yl)prolinamide 10. In the case of the bis-heterocycle 8, treatment with HCOONH4 and Pd/C in MeOH gave the debenzylated product 12.
Studies on the synthesis and some reactions of (S)-proline hydrazides
Mloston, Grzegorz,Pieczonka, Adam M.,Wroblewska, Aneta,Linden, Anthony,Heimgartner, Heinz
experimental part, p. 795 - 801 (2012/09/07)
A convenient synthesis of (S)-proline hydrazide 2a via the reaction of ethyl (S)-N-benzylprolinate with hydrazine hydrate and subsequent deprotection of (S)-N-benzyl proline hydrazide 5 is described. The latter, in methanolic solution, reacted with aromatic aldehydes as well as with cycloaliphatic ketones at room temperature to give the corresponding hydrazones of type 7 in good yields. The structure of the product with furan-2-carbaldehyde 7b, proving the (E)-configuration of the hydrazone, was established by X-ray crystallography. In the case of the unprotected (S)-proline hydrazide 2a, the analogous reaction with aromatic aldehydes led either to the expected hydrazones 7 or the 1H-pyrrolo[1,2-c]imidazol-1-one derivatives 8, depending on the reaction conditions. The latter were formed via a secondary cyclocondensation of the initially formed 7 with a second molecule of the aldehyde. Whereas the reaction of (S)-N-benzyl proline hydrazide 5 with butyl isocyanate and isothiocyanate gave the corresponding semicarbazide and thiosemicarbazide, respectively, of type 9, the unprotected (S)-proline hydrazide 2a yielded the 1:2 adducts 10. Thiosemicarbazide 9b underwent cyclization reactions under basic (NaOH) and acidic (H2SO4) conditions to yield (S)-prolinyl- substituted 1,2,4-triazole-3-thione 11 and 1,3,4-thiadiazole-2-amine 12, respectively.
Pyrrolidine amides of pyrazolodihydropyrimidines as potent and selective KV1.5 blockers
Lloyd, John,Finlay, Heather J.,Vacarro, Wayne,Hyunh, Tram,Kover, Alexander,Bhandaru, Rao,Yan, Lin,Atwal, Karnail,Conder, Mary Lee,Jenkins-West, Tonya,Shi, Hong,Huang, Christine,Li, Danshi,Sun, Huabin,Levesque, Paul
scheme or table, p. 1436 - 1439 (2010/07/02)
Design and synthesis of pyrazolodihydropyrimidines as KV1.5 blockers led to the discovery of 7d as a potent and selective antagonist. This compound showed atrial selective prolongation of effective refractory period in rabbits and was selected for clinical development.
