HRP970036A2 - Novel derivatives of 3-bromo and 3,3-dibromo-4-oxo-1-azetidines, process for the preparation thereof and their use - Google Patents
Novel derivatives of 3-bromo and 3,3-dibromo-4-oxo-1-azetidines, process for the preparation thereof and their useInfo
- Publication number
- HRP970036A2 HRP970036A2 HRP970036A HRP970036A2 HR P970036 A2 HRP970036 A2 HR P970036A2 HR P970036 A HRP970036 A HR P970036A HR P970036 A2 HRP970036 A2 HR P970036A2
- Authority
- HR
- Croatia
- Prior art keywords
- hydrogen
- bromine
- halogen
- coor4
- me2c
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 8
- 238000002360 preparation method Methods 0.000 title claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 52
- 239000001257 hydrogen Substances 0.000 claims description 52
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 34
- 229910052794 bromium Chemical group 0.000 claims description 34
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 28
- 229910052736 halogen Inorganic materials 0.000 claims description 28
- 150000002367 halogens Chemical group 0.000 claims description 28
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 23
- 150000002431 hydrogen Chemical group 0.000 claims description 22
- -1 nitroxy group Chemical group 0.000 claims description 19
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 15
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 14
- 125000003545 alkoxy group Chemical group 0.000 claims description 12
- 238000006243 chemical reaction Methods 0.000 claims description 10
- 125000006239 protecting group Chemical group 0.000 claims description 10
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- 125000000623 heterocyclic group Chemical group 0.000 claims description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 150000001875 compounds Chemical class 0.000 claims description 4
- 229910001494 silver tetrafluoroborate Inorganic materials 0.000 claims description 4
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 claims description 4
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims description 2
- 150000001298 alcohols Chemical class 0.000 claims description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims description 2
- 150000001408 amides Chemical class 0.000 claims description 2
- 150000001412 amines Chemical class 0.000 claims description 2
- 150000008064 anhydrides Chemical class 0.000 claims description 2
- 230000000844 anti-bacterial effect Effects 0.000 claims description 2
- 150000001805 chlorine compounds Chemical class 0.000 claims description 2
- 229910001961 silver nitrate Inorganic materials 0.000 claims description 2
- 125000001246 bromo group Chemical group Br* 0.000 claims 7
- 239000013543 active substance Substances 0.000 claims 1
- 239000002671 adjuvant Substances 0.000 claims 1
- 150000001539 azetidines Chemical class 0.000 claims 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
- 239000000047 product Substances 0.000 description 5
- FDSGHYHRLSWSLQ-UHFFFAOYSA-N dichloromethane;propan-2-one Chemical compound ClCCl.CC(C)=O FDSGHYHRLSWSLQ-UHFFFAOYSA-N 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- JPYQFYIEOUVJDU-UHFFFAOYSA-N beclamide Chemical compound ClCCC(=O)NCC1=CC=CC=C1 JPYQFYIEOUVJDU-UHFFFAOYSA-N 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- NWPMSXLAMMMLCC-UHFFFAOYSA-N [N].O=C1CCN1 Chemical compound [N].O=C1CCN1 NWPMSXLAMMMLCC-UHFFFAOYSA-N 0.000 description 1
- MNFORVFSTILPAW-UHFFFAOYSA-N azetidin-2-one Chemical compound O=C1CCN1 MNFORVFSTILPAW-UHFFFAOYSA-N 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Description
Izum se odnosi na derivate 3-bromo-, i 3,3-dibromo-4-okso-1-azetidina, postupke za njihovo dobivanje i upotrebu i to je nadopuna hrvatske patentne prijave pod brojem 960061 A s prioritetom od 06.02.1996. godine pod nazivom "Novi derivati 3-bromo-, i 3,3-dibromo-4-okso-1-azetidina, postupci priprave i upotreba". The invention relates to 3-bromo- and 3,3-dibromo-4-oxo-1-azetidine derivatives, procedures for their preparation and use, and it is a supplement to Croatian patent application number 960061 A with priority from 06.02.1996. entitled "New derivatives of 3-bromo- and 3,3-dibromo-4-oxo-1-azetidine, methods of preparation and use".
Predmet ovog izuma se odnosi na derivate 3-bromo-, i 3,3-dibromo-4-okso-1-azetidina opće formule I u kojoj The subject of this invention relates to 3-bromo- and 3,3-dibromo-4-oxo-1-azetidine derivatives of the general formula I in which
[image] [image]
R1 je vodik ili brom R 1 is hydrogen or bromine
R2 je vodik ili brom R 2 is hydrogen or bromine
R3 je vodik, Me2C=C-COOR4; -C(COOR4)=C(Me)CH2Y; R3 is hydrogen, Me2C=C-COOR4; -C(COOR4)=C(Me)CH2Y;
Me2C=C-CONHR5; -CH(CONHR5)-C(Me)=CH2; Me2C=C-CONHR5; -CH(CONHR5)-C(Me)=CH2;
[image] [image]
kod čega je where is it
R4 je vodik, metil, benzil ili neka druga zaštitna grupa R4 is hydrogen, methyl, benzyl or some other protecting group
R5 je vodik, alkil, alkilaril, heterociklički prsten R5 is hydrogen, alkyl, alkylaryl, heterocyclic ring
Y je halogen Y is halogen
X je halogen, alkoksi grupa, nitroksi grupa X is a halogen, an alkoxy group, a nitroxy group
Daljnji predmet ovog izuma je postupak za pripravu derivata 3-bromo-, i 3,3-dibromo-4-okso-1-azetidina opće formule I u kojoj radikali imaju gore navedeno značenje a koji se mogu pripraviti polazeći od derivata opće formule I u kojoj X je halogen reakcijom sa srebrnim tetrafluoroboratom i alkoholima napr. 2-propanolom pri čemu nastaje derivat opće formule I, u kojoj je X alkoksi grupa odn. izopropoksi grupa, a A further subject of this invention is a process for the preparation of 3-bromo- and 3,3-dibromo-4-oxo-1-azetidine derivatives of the general formula I in which the radicals have the above-mentioned meaning and which can be prepared starting from the derivatives of the general formula I in where X is a halogen by reaction with silver tetrafluoroborate and alcohols e.g. with 2-propanol, whereby a derivative of the general formula I is formed, in which X is an alkoxy group or isopropoxy group, a
R1 je vodik ili brom R 1 is hydrogen or bromine
R2 je vodik ili brom R 2 is hydrogen or bromine
R3 je vodik, Me2C=C-COOR4; -C(COOR4)=C(Me)CH2Y; R3 is hydrogen, Me2C=C-COOR4; -C(COOR4)=C(Me)CH2Y;
Me2C=C-CONHR5; -CH(CONHR5)-C(Me)=CH2; Me2C=C-CONHR5; -CH(CONHR5)-C(Me)=CH2;
[image] [image]
kod čega je where is it?
R4 je vodik, metil, benzil ili neka druga zaštitna grupa, R4 is hydrogen, methyl, benzyl or some other protecting group,
R5 je vodik, alkil, alkilaril, heterociklički prsten R5 is hydrogen, alkyl, alkylaryl, heterocyclic ring
Y je halogen Y is halogen
ili se derivati opće formule I u kojoj je X halogen, a radikali imaju gore navedeno značenje podvrgnu reakciji sa srebrnim nitratom u 2-propanolu, pri čemu nastaje derivat opće formule I u kojoj X je nitroksi grupa, a or the derivatives of the general formula I in which X is halogen and the radicals have the above meaning are subjected to a reaction with silver nitrate in 2-propanol, whereby a derivative of the general formula I is formed in which X is a nitroxy group, and
R1 je vodik ili brom R 1 is hydrogen or bromine
R2 je vodik ili brom R 2 is hydrogen or bromine
R3 je vodik, Me2C=C-COOR4; -C(COOR4)=C(Me)CH2Y; R3 is hydrogen, Me2C=C-COOR4; -C(COOR4)=C(Me)CH2Y;
Me2C=C-CONHR5; -CH(CONHR5)-C(Me)=CH2; Me2C=C-CONHR5; -CH(CONHR5)-C(Me)=CH2;
[image] [image]
kod čega je where is it
R4 je vodik, metil, benzil ili neka druga zaštitna grupa, R4 is hydrogen, methyl, benzyl or some other protecting group,
R5 je vodik, alkil, alkilaril, heterociklički prsten R5 is hydrogen, alkyl, alkylaryl, heterocyclic ring
Y je halogen Y is halogen
ili se derivati opće formule I u kojoj je or the derivatives of the general formula I in which
R1 je vodik ili brom R 1 is hydrogen or bromine
R2 je vodik ili brom R 2 is hydrogen or bromine
R3 je Me2C=C-COOR4; -C(COOR4)=C(Me)CH2Y; R3 is Me2C=C-COOR4; -C(COOR4)=C(Me)CH2Y;
kod čega je where is it
R4 benzil ili neka druga zaštitna grupa, R4 benzyl or some other protecting group,
Y je halogen Y is halogen
X je halogen, alkoksi grupa, nitroksi grupa X is a halogen, an alkoxy group, a nitroxy group
podvrgnu reakciji uklanjanja zaštitne skupine, napr. benzila s aluminijevim trikloridom, pri čemu nastaje produkt opće formule I u kojem je subjected to a protective group removal reaction, e.g. of benzyl with aluminum trichloride, resulting in a product of the general formula I in which
R1 je vodik ili brom R 1 is hydrogen or bromine
R2 je vodik ili brom R 2 is hydrogen or bromine
R3 je Me2C=C-COOR4; -C(COOR4)=C(Me)CH2Y; kod čega je R3 is Me2C=C-COOR4; -C(COOR4)=C(Me)CH2Y; where is it?
R4 je vodik R4 is hydrogen
Y je halogen Y is halogen
X je halogen, alkoksi grupa, nitroksi grupa X is a halogen, an alkoxy group, a nitroxy group
Dobiveni se derivati opće formule I u kojoj je Derivatives of the general formula I are obtained in which
R1 je vodik ili brom R 1 is hydrogen or bromine
R2 je vodik ili brom R 2 is hydrogen or bromine
R3 je Me2C=C-COOR4; -C(COOR4)=C(Me)CH2Y, R3 is Me2C=C-COOR4; -C(COOR4)=C(Me)CH2Y,
kod čega je where is it
R4 je vodik R4 is hydrogen
Y je halogen Y is halogen
X je halogen, alkoksi grupa, nitroksi grupa X is a halogen, an alkoxy group, a nitroxy group
prevedu opće poznatim metodama u odgovarajuće amide napr. reakcijama odgovarajućih mješovitih anhidrida ili kiselinskih klorida s aminima, pri čemu nastaju derivati opće formule I converted by generally known methods into corresponding amides, e.g. reactions of the corresponding mixed anhydrides or acid chlorides with amines, whereby derivatives of the general formula I are formed
R1 je vodik ili brom R 1 is hydrogen or bromine
R2 je vodik ili brom R 2 is hydrogen or bromine
Me2C=C-CONHR5;-C(CONHR5)=C(Me)CH2Y; Me2C=C-CONHR5;-C(CONHR5)=C(Me)CH2Y;
kod čega je where is it
R5 je vodik, alkil, alkilaril, heterociklički prsten R5 is hydrogen, alkyl, alkylaryl, heterocyclic ring
Y je halogen Y is halogen
X je halogen, alkoksi grupa, nitroksi grupa X is a halogen, an alkoxy group, a nitroxy group
Predmet ovog izuma su novo sintetizirane supstancije koje se pripravljaju polazeći od derivata sulfinskih kiselina azetidinona, najbolje 2-sulfinamida azetidinona sa raznim supstituentima na azetidinonskom dušiku. Predmet ovog izuma je i novi postupak, koji je jednostavan i lako provediv, kojim se nove supstancije dobivaju u visokom iskorištenju. The subject of this invention are newly synthesized substances that are prepared starting from azetidinone sulfinic acid derivatives, preferably 2-sulfinamide azetidinone with various substituents on the azetidinone nitrogen. The subject of this invention is also a new process, which is simple and easy to implement, by which new substances are obtained in high yield.
Daljnji predmet ovog izuma se odnosi na upotrebu ovih spojeva kao kompo-nenata u farmaceutskim preparatima s antibakterijskim djelovanjem. A further subject of this invention relates to the use of these compounds as components in pharmaceutical preparations with antibacterial activity.
Izum je ilustriran sljedećim primjerima koji ni u čemu ne ograničavaju širinu izuma. The invention is illustrated by the following examples, which in no way limit the scope of the invention.
Primjer 1 Example 1
Benzilni ester 3,3-dibromo-2-izopropoksi-alfa-( 1 -metiletiliden)-4-okso-1-azetidin octene kiseline. 3,3-Dibromo-2-isopropoxy-alpha-(1-methylethylidene)-4-oxo-1-azetidine acetic acid benzyl ester.
U otopinu benzilnog estera 2,3,3-tribromo-1-(1-metiletiliden)-4-okso-azetidin octene kiseline (0.248 g; 0.5 mmol) u 2-propanolu ( p.a.,10 ml), se doda srebrni tetrafluoroborat (0.388 g; 2.0 mmol) i miješa na sobnoj temperaturi. Nakon 10 minuta suspenzija se pretvori u otopinu i reakcija je gotova za jedan sat. Otopina se filtrira, a lug upari do suhog ostatka. Uparenom ostatku se doda metilen klorid, talog filtrira, upari i ponovo doda metilen klorid, talog filtrira, a lug upari do suhog ostatka. Upareni ostatak se čisti kromatografijom na koloni silikagela sa sistemom otapala etil acetat-metanol (95:5). Prinos nakon sušenja na visoki vakuum 0.130 g (54%). To a solution of 2,3,3-tribromo-1-(1-methylethylidene)-4-oxo-azetidine acetic acid benzyl ester (0.248 g; 0.5 mmol) in 2-propanol (p.a., 10 ml), silver tetrafluoroborate ( 0.388 g; 2.0 mmol) and stir at room temperature. After 10 minutes, the suspension turns into a solution and the reaction is complete in one hour. The solution is filtered, and the lye is evaporated to a dry residue. Methylene chloride is added to the evaporated residue, the residue is filtered, evaporated and methylene chloride is added again, the residue is filtered, and the lye is evaporated to a dry residue. The evaporated residue is purified by chromatography on a silica gel column with the solvent system ethyl acetate-methanol (95:5). Yield after high vacuum drying 0.130 g (54%).
Rf 0.55 (metilen klorid) Rf 0.55 (methylene chloride)
IR (100%): 3350(w), 2980(w), 1800(vs), 1790(vs), 1730(vs), 1655(m), 1500(m), 1455(m), 1390(vs), 1370(vs), 1335(m), 1295(s), 1265(s), 1220(vs), 1165(vs), 1100(vs), 1020(s), 700(vs) cm-1. IR (100%): 3350(w), 2980(w), 1800(vs), 1790(vs), 1730(vs), 1655(m), 1500(m), 1455(m), 1390(vs) , 1370(vs), 1335(m), 1295(s), 1265(s), 1220(vs), 1165(vs), 1100(vs), 1020(s), 700(vs) cm-1.
1HNMR (300 MHz, CDC13) δ: 1.085 i 1.216 (2d, 6H, J=6.2 MHz, Me2-CH,), 1.982 i 2.298 (2s, 6H, 2Me), 3.700-3.741 (m, 1H, J=6.2Hz, CH), 5.117 i 5.292 (2H, 2d, J=12 Hz, CH2Ph), 5.286 (s, 1H, C2-H), 7.331-7.392 (m, 5H, Ar) ppm. 1HNMR (300 MHz, CDCl3) δ: 1.085 and 1.216 (2d, 6H, J=6.2 MHz, Me2-CH,), 1.982 and 2.298 (2s, 6H, 2Me), 3.700-3.741 (m, 1H, J=6.2 Hz, CH), 5.117 and 5.292 (2H, 2d, J=12 Hz, CH2Ph), 5.286 (s, 1H, C2-H), 7.331-7.392 (m, 5H, Ar) ppm.
Primjer 2 Example 2
Benzilamid 2,3,3-tribromo-alfa-( 1 -metiletiliden)-4-okso-1-azetidin octene kiseline Acetic acid 2,3,3-tribromo-alpha-(1-methylethylidene)-4-oxo-1-azetidine benzylamide
2,3,3-Tribromo-alfa-( 1-metiletiliden)-4-okso-1-azetidin octena kiselina (0.406 g, 0.001 mola) se otopi u metilen kloridu (oprani vodom, suhi, 20 ml), ohladi na -10°C, doda tionil klorid (4 ml) i miješa jedan sat, a zatim još jedan sat na sobnoj temperaturi. Zatim se rekcijska smjesa upari, suhom ostatku doda benzen (2 puta po 20 ml i svaki puta upari). Ostataku otopljenom u metilen kloridu (20 ml) se doda benzilamin (0.30 ml,0.0027 mola) otopljen u 10 ml metilen klorida do pH 7.0 i miješa na sobnoj temperaturi jedan sat. Talog se odsiše, a lug upari do suhog ostatka (0.241 g). Dobiveni je produkt čišćen "flash" kromatografijom s metilen kloridom kao eluentom, nakon čega je izoliran uljasti produkt, koji se sušenjem na 0.01 mm Hg pretvara u pjenu (0.209 g). Dio produkta zaostao na sloju silikagela je eluiran metanolom, uparen do suha i ponovo čišćen kromatografijom na koloni sa metilen kloridom-acetonom (10:0.3). Dobiveno je još 0.074g produkta. Ukupno je dobiveno 0.283g (57.2%) 2,3,3-Tribromo-alpha-(1-methylethylidene)-4-oxo-1-azetidine acetic acid (0.406 g, 0.001 mol) is dissolved in methylene chloride (washed with water, dry, 20 ml), cooled to - 10°C, add thionyl chloride (4 ml) and stir for one hour, then another hour at room temperature. Then, the reaction mixture is evaporated, benzene is added to the dry residue (2 times for 20 ml and evaporated each time). Benzylamine (0.30 ml, 0.0027 mol) dissolved in 10 ml of methylene chloride was added to the residue dissolved in methylene chloride (20 ml) until pH 7.0 and stirred at room temperature for one hour. The precipitate is filtered off with suction, and the lye is evaporated to a dry residue (0.241 g). The obtained product was purified by "flash" chromatography with methylene chloride as eluent, after which an oily product was isolated, which turned into foam (0.209 g) by drying at 0.01 mm Hg. Part of the product remaining on the silica gel layer was eluted with methanol, evaporated to dryness and purified again by column chromatography with methylene chloride-acetone (10:0.3). Another 0.074g of product was obtained. A total of 0.283g (57.2%) was obtained.
Rf 0.50 metilen klorid-aceton (10:0.3) Rf 0.50 methylene chloride-acetone (10:0.3)
IR(film): 3305(m), 1800(vs), 1670-1635(vs), 1535-1510(s), 1370(vs), 1135(s), 1100(s), 810(s), 705(s) cm-1. IR(film): 3305(m), 1800(vs), 1670-1635(vs), 1535-1510(s), 1370(vs), 1135(s), 1100(s), 810(s), 705 (s) cm-1.
1H NMR (CDCI3) (300 MHz) δ: 1H NMR (CDCl3) (300 MHz) δ:
1.876(s,3H, Me), 2.085 (s, 3H, Me), 4.50-4.52(m, 2H, NHCH2Ph, sa D2O 4.506 2d, centar), 6.010 (bs, 1H, NH, nestaje sa D2O), 6.301(s, 1H, C2-H), 7.303-7.376(m, 5H, Ar) ppm. 1.876(s,3H, Me), 2.085 (s, 3H, Me), 4.50-4.52(m, 2H, NHCH2Ph, with D2O 4.506 2d, center), 6.010 (bs, 1H, NH, vanishes with D2O), 6.301 (s, 1H, C2-H), 7.303-7.376(m, 5H, Ar) ppm.
MS FAB+ MW 492, MH+ 493, (3Br) MS FAB+ MW 492, MH+ 493, (3Br)
Primjer 3 Example 3
Benzilamid 3,3-dibromo-2-metoksi-alfa-(l-metiletiliden)-4-okso-1-azetidin octene kiseline Acetic acid 3,3-dibromo-2-methoxy-alpha-(1-methylethylidene)-4-oxo-1-azetidine benzylamide
U otopinu benzilamida 2,3,3-tribromo-alfa-(1-metiletiliden)-4-okso-1-azetidin octene kiseline (0.074 g, 0.15 mmola) u MeOH (5 ml) doda se srebrni tetrafluoroborat (0.117g; 0.60 mmola) i miješa na sobnoj temperaturi. Kad je reakcija gotova, filtrira se, doda metilen klorid, i ponovo filtrira i filtrat upari do suha (0.136 g). Supstancija se čisti kromatografijom na koloni silikagela sa sistemom otapala metilen klorid-aceton (10:0.3); Prinos 0.033 g (bijeli sirup). Iskorištenje 50%. Silver tetrafluoroborate (0.117g; 0.60) was added to a solution of benzylamide 2,3,3-tribromo-alpha-(1-methylethylidene)-4-oxo-1-azetidine acetic acid (0.074 g, 0.15 mmol) in MeOH (5 ml). mmol) and stir at room temperature. When the reaction is complete, it is filtered, methylene chloride is added, filtered again and the filtrate is evaporated to dryness (0.136 g). The substance is purified by chromatography on a silica gel column with the solvent system methylene chloride-acetone (10:0.3); Yield 0.033 g (white syrup). Utilization 50%.
Rf 0.4 metilen klorid-aceton (10:0.3) Rf 0.4 methylene chloride-acetone (10:0.3)
IR(film): 3335(m), 1800(vs), 1675-1630(s), 1520(s), 1380(vs), !!20(s9, 700(vs) cm-1. IR(film): 3335(m), 1800(vs), 1675-1630(s), 1520(s), 1380(vs), !!20(s9, 700(vs) cm-1.
1H NMR (CDC13) (300 MHz) δ: 1.873 (s, 3H, Me), 2.156 (s, 3H, Me), 3.552 (s, 3H, OMe), 4.468-4.495 (m, 2H, NHCH2Ph, sa D2O 2d, 4.480 centar), 5.102 (s, 1H, C2-H) 6.418 (b, 1H, NH, nestaje sa D2O), 7.28-7.36 (m, 5H, Ar) ppm. 1H NMR (CDCl3) (300 MHz) δ: 1.873 (s, 3H, Me), 2.156 (s, 3H, Me), 3.552 (s, 3H, OMe), 4.468-4.495 (m, 2H, NHCH2Ph, with D2O 2d, 4.480 center), 5.102 (s, 1H, C2-H) 6.418 (b, 1H, NH, disappears with D2O), 7.28-7.36 (m, 5H, Ar) ppm.
Claims (6)
Priority Applications (12)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HRP970036 HRP970036A2 (en) | 1997-01-20 | 1997-01-20 | Novel derivatives of 3-bromo and 3,3-dibromo-4-oxo-1-azetidines, process for the preparation thereof and their use |
| SK138-97A SK13897A3 (en) | 1996-02-06 | 1997-01-31 | 3-bromo- and 3,3-dibromo-4-oxo-1-azetidines, method for preparation thereof and their use |
| EP97101644A EP0791580A3 (en) | 1996-02-06 | 1997-02-03 | Novel derivatives of 3-bromo and 3,3-dibromo-4-oxo-1-azetidines, processes for the preparation thereof and their use |
| CN97103186A CN1164531A (en) | 1996-02-06 | 1997-02-05 | Novel derivatives of 3-bromo-and 3,3-dibromo-4-oxo-1-azetidines, processes for preparation thereof and their use |
| SI9700028A SI9700028A (en) | 1996-02-06 | 1997-02-05 | Novel derivatives of 3-bromo- and 3,3-dibromo-4-oxo-1-azetidines, their preparation processes and their use |
| BG101202A BG62565B1 (en) | 1996-02-06 | 1997-02-05 | New derivatives of 3-brom- and 3,3-dibrom-4-oxo-1-azetidines, method for their preparation and application |
| CA002196909A CA2196909A1 (en) | 1996-02-06 | 1997-02-05 | Derivatives of 3-bromo- and 3, 3-dibromo-4-oxo-1-azetidines, processes for the preparation thereof and their use |
| CZ97346A CZ34697A3 (en) | 1996-02-06 | 1997-02-05 | Derivatives of 3-bromo and 3,3-dibromo-4-oxo-1-azetidines, process of their preparation and their use |
| PL97318346A PL318346A1 (en) | 1996-02-06 | 1997-02-06 | Novel derivatives of 3-bromine and 3,3-dibromine 4-oxo-1-azetidines, method of obtaining them and pharmaceutic composition |
| HU9700366A HUP9700366A3 (en) | 1996-02-06 | 1997-02-06 | Novel derivatives of 3-bromo- and 3,3 dibromo-4-oxo-1-azetidines, process for the preparation thereof and pharmaceutical compositions containing the same |
| JP9023594A JPH09227511A (en) | 1996-02-06 | 1997-02-06 | New 3-bromo-and 3,3,-dibromo-4-oxo-1-azetidine derivatives, its production and medicinal composition containing the same |
| US08/796,708 US5843939A (en) | 1996-02-06 | 1997-02-06 | Derivatives of 3-bromo- and 3,3-dibromo-4-oxo-1-azetidines, processes for the preparation thereof and their use |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HRP970036 HRP970036A2 (en) | 1997-01-20 | 1997-01-20 | Novel derivatives of 3-bromo and 3,3-dibromo-4-oxo-1-azetidines, process for the preparation thereof and their use |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP970036A2 true HRP970036A2 (en) | 1998-04-30 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP970036 HRP970036A2 (en) | 1996-02-06 | 1997-01-20 | Novel derivatives of 3-bromo and 3,3-dibromo-4-oxo-1-azetidines, process for the preparation thereof and their use |
Country Status (1)
| Country | Link |
|---|---|
| HR (1) | HRP970036A2 (en) |
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1997
- 1997-01-20 HR HRP970036 patent/HRP970036A2/en not_active Application Discontinuation
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