An improved process of separation of R- and S-timolol

Diastereomeric timolol tartrates 4 are obtained in a one-pot synthesis from the racemic base 2 and optically active O,O-diacetyl- or O,O-dibenzoyltartaric anhydrides 3 , as only one of the diastereomers precipitates from acetone solution. Acidic hydrolysis as the corresponding 4 leads to timolol in high yield and optical purity.     

Nitrogen bridgehead compounds. Part 70. Studies on quinolizine derivatives. Part 4. Ultraviolet-visible spectra and chemical properties of some quinolizine derivatives and their monocyclic tautomers

Ultraviolet-visible spectra of 4-oxo 1 and 4-imino 2 quinolizines or their monocyclic tautomers 3, 4 have been studied in neutral, acidic and basic ethanolic solution as well as in dimethyl sulfoxide and chloroform. Ring B of 4-oxo and 6-unsubstituted 4-imino compounds can be cleaved by sodium ethanolate more or less easily. Ring B of 6-methyl-4-iminoquinolizines is very unstable and they are present mainly in the monocyclic form which are partly dissociated in ethanol and dimethyl sulfoxide especially in higher dilution or in the presence of sodium ethanolate. In dilute acidic ethanol or chloroform, the dissociation is suppressed and in the latter solvent and in some cases, absorption bands can be observed due to a small amount of the 4-imino-6-methylquinolizines. In acidic solution of compounds 3B=C, 3D, 4E, 4F=G having simultaneously cyano and ethoxycarbonyl groups in 1 and 3 position, not simple reprotonation occurs but irreversible changes can be observed.     

Nitrogen bridgehead compounds part 14. Acylation of ethyl 6-methyl-4-oxo- -6,7,8,9-tetrahydro-pyrido(1,2-a)pyrimidine-3-carboxilate with isocyanates

The 9-carbamoyl derivatives /$\text{3}$–$\text{9}$/ can be prepared from title compound /$\text{1}$/ with isocyanates /$\text{2}$/. $\text{3}$–$\text{9}$ are mixtures of the cis /Z/ and trans /E/ imines and the enamine /e/. The equilibrium depends on the substituents R,X and on the solvent.     

Nitrogen bridgehead compounds part 21. Preparation of new quaternary 2,3a,6a-triazaphenalenium salts

The first representatives of a new ring system, the 2,3a,6a-triazaphenalenium quaternary salts are prepared by the cycloaddition of tetrahydro-4H-pyrido[1,2-a] pyrimidin-4-ones containing an α-chloroenamine moiety with azomethines.     

Nitrogen bridgehead compounds. Part 88. Synthesis of 3H, 7H-[1,4]diazepino[3,4-b]quinazoline-3,7-diones

3H,7H-[1,4]Diazepino[3,4-b]quinazolone-3,7-diones 9, 11 were synthesized starting from 2-(1-bromo-ethyl)quinazolin-4(3H)-ones 3 and 17 via 2-[1-(4-methoxyphenylamino)ethyl]quinazolin-4(3H)-ones 4 and 18. Cyclization of 3-[2-(1-bromoethyl)-4-oxo-3,4-dihydroquinazolin-3-yl)propionic acid 14 by the action of triethylamine provided the first representative of the tricyclic 7H-[1,4]oxazepino[3,4-b]quinazoline-3,7-dione system, compound 15. The new tricyclic derivatives 9, 11 and 15 are characterized by uv, ir and ¹H nmr spectroscopy.     

Nitrogen bridgehead compounds. Part 35. Structures of α-formyl-2,3-polymethylene-3,4-dihydroquinazolin-4-ones

The structures of the title compounds bearing a five-, six- or seven-membered A ring have been investigated by uv and ¹H and ¹³C nmr spectroscopy. The imine-enol-enamine (I-II-III) tautomerism of these compounds depends greatly on the ring size. A significant solvent-dependence is observed only for the five-membered-ring compounds 1 and 2 , which in ethanolic solution exist predominantly in the imine form I, and in chloroform solution in the enol form II. The compounds with a six-membered A ring, 3 and 4 , are mainly in the enamine form III. On protonation, 3 and 4 change into the E and Z isomeric mixture of the enol tautomer II. The seven-membered-ring compound 5 is a mixture of the imine I and the enamine III tautomers.     

Nitrogen bridgehead compounds. Part 55 Synthesis of substituted 7,8-dihydro-5H,13H-indolo[2′,3′:3,4]pyrido[2,1-b]quinazolin-5-ones

Fischer indolization of 6-arylhydrazono-6,7,8,9-tetahydro-11H-pyrido[2,1-b]quinazolin-11-ones 1 afforded substituted 7,8-dihydro-5H,13H-indolo[2′,3′:3,4]pyrido[2,1-b]quinazolin-5-ones 3-12 in high yields.     

Nitrogen bridgehead compounds. Part 76 Synthesis and stereochemistry of ethyl 9-benzylidene-6,7,8,9-tetrahydro-2-oxo-2H- and 4-oxo-4H-pyrido[1,2-a]pyrimidine-3-carboxylates and their homologues

Ethyl 4-oxo-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidine-3-carboxylates 1–4 , their piperidine ring homologues 5–6 and their 2-oxo isomers 7–9 were reacted with benzaldehyde. At low temperature, kinetically stable addition products were formed. Thermodynamically stable condensation products were obtained at higher temperature, which were also formed when the addition products were refluxed in benzene. The 9-benzyl derivatives were prepared by the hydrogenation of the condensation products over Pd/C. The stereochemical features of the new compounds were determined via ¹H and ¹³C nmr chemical shift and coupling constant analysis and NOE measurements.     

Ring transformation of 4-oxo-1,6,7,8-tetrahydro-4H-pyrido[1,2-a]-pyrimidine-3-carboxamide

The title compound /$\text{3}$/ may be transformed into the 3-/methylaminomethylene/--2,3,6,7,8,9-hexahydro-4H-pyrido[1,2-a]pyrimidine-2,4-dione /$\text{5}$E, $\text{5}$Z/ which is in equilibrium with the 1,2,3,6,7,8-hexahydro tautomer /$\text{8}$E, $\text{8}$Z/ in DMSO-d₆.     

Suzuki-Miyaura cross-coupling reactions of halo derivatives of 4H-pyrido[1,2-a]pyrimidin-4-ones

The palladium-catalyzed Suzuki-Miyaura cross-coupling reactions of halo derivatives of 4H-pyrido[1,2-a]pyrimidin-4-one with (het)arylboronic acids allow easy access to (het)aryl and vinyl derivatives of this bicycle in good to excellent yields, even from chloro derivatives. The sequence of reactivity of the halogen in the different positions of the ring system was also investigated. 6-Phenyl-4H-pyrido[1,2-a]pyrimidin-4-one could be prepared by thermal cyclization of isopropylidene (6-phenylpyrid-2-ylamino)methylenemalonate, together with a small amount of 7-phenyl-1,4-dihydro-1,8-naphthyridin-4-one.