- Solid phase synthesis of hydroxy benzothiazepinones through cyclative release under thermolysis
-
Hydroxy benzothiazepinones were synthesized by a simple procedure involving epoxidation of polymer bound cinnamic acids followed by nucleophilic opening of the resulting glycidic ester by o-aminothiophenol to afford the intermediate hydroxy anilino-esters which underwent cyclization cleavage on heating in DMF to release the product completely.
- Sampath Kumar,Pawan Chakravarthy,Shesha Rao,Joyasawal, Sipak,Yadav
-
p. 888 - 889
(2007/10/03)
-
- Process for preparing an optically active phenylglycidyl acid derivative
-
The invention relates to a process for preparing an optically active trans-compound having formula (1), in which R represents a phenyl group, whether or not substituted, preferably p-methoxyphenyl, and A is derived from an optically active compound, in which an aldehyde having formula (2), in which R is as defined above, is, in the presence of a base, brought into contact with an optically active acetyl compound having formula (3), in which X represents a leaving group and in which A is derived from an amino alcohol, preferably a beta -amino alcohol having a rigid structure. Particularly good results were obtained when use was made of a compound having formula (3), in which A is derived from an amino indanol compound having formula (4), in which R1 and R2 represent a (hetero)alkyl or (hetero)aryl group, whether or not substituted, having 1-10 C atoms, or R1 and R2 constitute an aromatic or aliphatic ring together with the N atom to which they are bound, in particular in which R1 and R2 each independently of one another represent methyl, ethyl, isopropyl, n-propyl, n-butyl, allyl, benzyl or tosyl.
- -
-
-
- Optical resolution of a 1,5-benzothiazepine derivative, a synthetic intermediate of diltiazem, by preferential crystallization and diastereomeric salt formation
-
Practical preparation methods of an optically active intermediate of diltiazem, (+)-(2S,3S)-5-[2-(dimethylamino)ethyl]-2,3-dihydro-3-hydroxy-2- (4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one [(+)-7], have been developed by the use of physicochemical and chemical resolutions. 1) The salt of (+)-7 with 3-amino-4-hydroxy-benzenesulfonic acid (AHS), was found to exist as a conglomerate and could be reproducibly resolved into (+)-7·AHS and (-)- 7·AHS of 94-98% ee by a preferential crystallization procedure. 2) (+)- (1R)-3-Bromocamphor-9-sulfonic acid [(+)-BCS] was found to be an efficient resolving agent for (±)-7 and the diastereomeric resolution provided (+)- 7·(+)-BCS·2H2O salt in >43% yield and >97% ee by fractional crystallization. It is presumed that the crystal water of (+)-7·(+)- BCS·2H2O plays an important role in the selective crystallization during this efficient resolution.
- Yamada, Shin-Ichi,Yoshioka, Ryuzo,Shibatani, Takeji
-
p. 1922 - 1927
(2007/10/03)
-
- Process for the preparation of a benzothiazepine
-
Process for the preparation of a 1,5-benzothiazepine derivative, or a salt thereof, of formula 1 where R1 represents H, an alkyl group or an alkoxy group and R2represents H or a halogen, in which process a propanoic acid derivative of formula 2 where R1and R2are as defined above and R3represents H or an alkyl group is subjected to an intramolecular cyclisation reaction in a non-halogenated solvent in the presence of a carboxylic acid. Preferably, R2is H and R1is OCH3.Trichloroacetic acid is preferablky used as α-chlorinated acid. The benzothiazepine obtained on cyclisation can be subjected to an alkylation reaction and/or an acylation reaction to obtain known pharmaceutical products, in particular diltiazem.
- -
-
-
- A microwave synthesis of the cis and trans isomers of 3-hydroxy-2-(4-methoxyphenyl)-2,3-dihydro-1,5-benzothiazepin-4(5H)-one : The influence of solvent and power output on the diastereoselectivity
-
A diastereoselective one-pot synthesis and the trans- and cis-3-hydroxy-2-(4-methoxyphenyl)-2,3-dihydro-1,5-benzothiazepin-4(5H) -one nucleus, a key intermediate in the preparation of the calcium channel blocker Diltiazem, is carried out under microwave irradiation in an open vessel. Control of the diastereoselectivity is achieved by varying the reaction time and power output as well as the nature of the solvent.
- Vega, Juan A.,Cueto, Senida,Ramos, Andres,Vaquero, Juan J.,Garcia-Navio, Jose L.,Alvarez-Builla, Julio,Ezquerra, Jesus
-
p. 6413 - 6416
(2007/10/03)
-
- Enantiomer associations in the crystal structures of racemic and (2S,3R)-(-)-3-hydroxy-2-(4-methoxyphenyl)-2,3-dihydro-1,5-benzothiazepin-4(5H)- one
-
The crystal structures of racemic and (2S,3R)-(-)-3-hydroxy-2-(4-methoxyphenyl)-2,3-dihydro-1,5-benzothiazepin-4(5H)- one (C16H15NO3S) have been determined in order to compare the interactions between molecules of the same and opposite chirality. The enantiomeric associations observed in these two crystal structures are analysed, relating the differences to those found in the equivalent diastereomers, (2R, 3R) and/or (2S, 3S). Single-crystal X-ray diffraction data were collected at low temperature with Cu Kα radiation (λ = 1.54184 A). Optically active: monoclinic, space group C2, with a = 24.726(3), b = 5.2426(5), c =12.0726(12) A, β - 112.979(9)°, V = 1440.8(5) A3, Z = 4, Dx= 1.389 g cm-3, μ = 20.35 cm-1, the refinement on 2918 observed reflections gave R=0.0271. Racemic: monoclinic, space group P21/n, with a = 13.308(3), b = 4.8474(8), c = 22.130(4) A, β = 91.782(14), V= 1426.9(5) A3, Z=4, Dx= 1.403 g cm-3, μ= 20.54 cm-1, refined to R = 0.0318 for 2753 observed reflections. An intramolecular hydrogen bond between the hydroxy and carbonyl groups appears to stabilize the benzothiazepinone ring in the (P,2S,3R) boat conformation with the hydroxy and methoxyphenyl substituents in equatorial positions. In both crystal structures two N-H...O hydrogen bonds connect the molecules into dimers. In the optically active compound the two molecules are related by a twofold axis, in the racemate by an inversion centre. The racemate contains an additional hydrogen bond which is reflected by its higher melting enthalpy compared with the optically active compound. The difference in the chiral discrimination in the solutions of the cis-and trans-diastereomers does not appear to have its origin in the strong (O-H...O, N-H...O) hydrogen bonds, but rather in the weak (C-H...O) interactions. Acta Chemica Scandinavica 1996.
- Marthi, Katalin,Larsen, Sine,Acs, Maria,Jaszay, Zsuzsa,Fogassy, Elemer
-
p. 906 - 913
(2007/10/03)
-
- cis-(±)-5-[2- (Dimethylamino)ethyl]-3-hydroxy-2-(4- methoxyphenyl )-2,3,4,5-tetrahydro-1,5-benzothiazepin-4-one
-
The title compound, C20H24N2O3S, is a drug intermediate of diltiazem. The molecule is stabilized by covalent bonding and weak hydrogen bonding, and the crystal packing is stabilized by hydrogen bonding. The seven-membered ring is distorted showing a twist-boat conformation. The methoxyphenyl and hydroxy groups are cis oriented with respect to one another, with the phenyl ring in an axial position. Intermolecular hydrogen bonding produces dimers in the crystal.
- Kumaradhas,Nirmala,Sridhar
-
p. 2595 - 2597
(2007/10/03)
-
- Carbohydrates as Chiral Auxiliaries in Asymmetric Darzens Reactions: Enantioselective Synthesis of the Benzothiazepine Ring System of Diltiazem
-
Carbohydrate alcohols 11 and 14, prepared from D-glucose and D-galactose, are employed as their chloro acetes 18 and 19 in the asymmetric Darzens glycidic ester condensation with p-anisaldehyde.Alcohol 11 induces modest diastereoselectivity (65:35) and af
- Nangia, Ashwini,Rao, P. Bheema,Madhavi, N.N.L.
-
p. 1716 - 1730
(2007/10/03)
-
- Stereoselective addition of 2-aminothiophenol to α-alkoxycinnamic acid derivatives - Alternative synthesis of (±)-diltiazem
-
A stereocontrolled synthesis of (±)-diltiazem by applying nucleophilic addition of 2-aminothiophenol to α-alkoxycinnamic acid derivatives is described.
- Miyata, Okiko,Shinada, Tetsuro,Naito, Takeaki,Ninomiya, Ichiya,Date, Tadamasa,Okamura, Kimio
-
p. 8119 - 8128
(2007/10/02)
-
- Glycidic acid ester and process of preparation
-
A process for the preparing a compound of the formula STR1 wherein R 1 and R 2 are each independently hydrogen, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, halogen, trifluoromethyl or nitro; or R 1 and R 2 taken together with the benzene ring to which they are attached are naphthalene, and Ar is p-lower alkoxy phenyl.which comprises reacting STR2 wherein R 1 and R 2 are as described above with the compound of the formula STR3 wherein Ar is as described above, in an aromatic organic compound. The intermediates formed by the process of the invention are useful in the production of thiazepin-4(5H)-ones which have activity as calcium channel blockers and accordingly are useful as agents for lowering blood pressure and agents for treating ischemia.
- -
-
-
- ENANTIOMER-ASSOCIATIONS INFLUENCING CHEMICAL REACTIVITY.
-
A comparative study for a ring-closure reaction in solution, melt and solid state is reported.The different behaviour of the different enantio-composition is explained on the basis of enantiomer-associate formation.
- Acs, M.,Gizur, T.,Peter, I.,Harsanyi, K.,Jaszay, Zs.,Fogassy, E.
-
p. 289 - 296
(2007/10/02)
-
- Reaction of 3-Phenylglycidic Esters. III. Reaction of cis-3-Arylglycidic Esters with Various Thiophenols
-
The reaction of the cis-3-arylglycidic esters 2 and 10 with thiophenols (3) has been investigated.The reactivity and stereoselectivity of the oxirane ring-opening of these cis-glycidic esters were lower than those of the trans-analogues (1 and 9).These tendencies were more apparent in the 4-MeO derivative (2).On the other hand, the tin-catalyzed reaction of 2 with 3a was highly stereospecific and afforded the cis-opening products (5a).Keywords - cis-3-arylglycidic ester; thiophenol; oxirane ring-opening; tin catalyst; stereoselectivity
- Hashiyama, Tomiki,Inoue, Hirozumi,Konda, Mikihiko,Takeda, Mikio
-
p. 1256 - 1259
(2007/10/02)
-