HRP930129A2 - N-subutituted derivatives of n-methyl-3-(p-trifluoromethylphenoxy) -3-phenylpropilamine and the process for the preparation thereof - Google Patents
N-subutituted derivatives of n-methyl-3-(p-trifluoromethylphenoxy) -3-phenylpropilamine and the process for the preparation thereof Download PDFInfo
- Publication number
- HRP930129A2 HRP930129A2 HRP930129A HRP930129A2 HR P930129 A2 HRP930129 A2 HR P930129A2 HR P930129 A HRP930129 A HR P930129A HR P930129 A2 HRP930129 A2 HR P930129A2
- Authority
- HR
- Croatia
- Prior art keywords
- methyl
- radical
- trifluoromethylphenoxy
- benzyl
- general formula
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 7
- 238000002360 preparation method Methods 0.000 title claims description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 12
- 150000001875 compounds Chemical class 0.000 claims description 11
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- RTHCYVBBDHJXIQ-UHFFFAOYSA-N N-methyl-3-phenyl-3-[4-(trifluoromethyl)phenoxy]propan-1-amine Chemical class C=1C=CC=CC=1C(CCNC)OC1=CC=C(C(F)(F)F)C=C1 RTHCYVBBDHJXIQ-UHFFFAOYSA-N 0.000 claims description 5
- 125000003118 aryl group Chemical group 0.000 claims description 4
- AOGYCOYQMAVAFD-UHFFFAOYSA-N chlorocarbonic acid Chemical compound OC(Cl)=O AOGYCOYQMAVAFD-UHFFFAOYSA-N 0.000 claims description 3
- 238000009833 condensation Methods 0.000 claims description 3
- 230000005494 condensation Effects 0.000 claims description 3
- 150000002148 esters Chemical class 0.000 claims description 3
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 claims description 3
- QULYNCCPRWKEMF-UHFFFAOYSA-N parachlorobenzotrifluoride Chemical compound FC(F)(F)C1=CC=C(Cl)C=C1 QULYNCCPRWKEMF-UHFFFAOYSA-N 0.000 claims description 3
- XXSDCGNHLFVSET-UHFFFAOYSA-N 3-(methylamino)-1-phenylpropan-1-ol Chemical class CNCCC(O)C1=CC=CC=C1 XXSDCGNHLFVSET-UHFFFAOYSA-N 0.000 claims description 2
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 2
- 125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 claims 5
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 12
- 238000005160 1H NMR spectroscopy Methods 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- FSXSEGYVGKNUIN-UHFFFAOYSA-N n-benzyl-n-methyl-3-phenyl-3-[4-(trifluoromethyl)phenoxy]propan-1-amine Chemical compound C=1C=CC=CC=1CN(C)CCC(C=1C=CC=CC=1)OC1=CC=C(C(F)(F)F)C=C1 FSXSEGYVGKNUIN-UHFFFAOYSA-N 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- BAYGVMXZJBFEMB-UHFFFAOYSA-N 4-(trifluoromethyl)phenol Chemical compound OC1=CC=C(C(F)(F)F)C=C1 BAYGVMXZJBFEMB-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- NXLNNXIXOYSCMB-UHFFFAOYSA-N (4-nitrophenyl) carbonochloridate Chemical compound [O-][N+](=O)C1=CC=C(OC(Cl)=O)C=C1 NXLNNXIXOYSCMB-UHFFFAOYSA-N 0.000 description 1
- RTHCYVBBDHJXIQ-MRXNPFEDSA-N (R)-fluoxetine Chemical compound O([C@H](CCNC)C=1C=CC=CC=1)C1=CC=C(C(F)(F)F)C=C1 RTHCYVBBDHJXIQ-MRXNPFEDSA-N 0.000 description 1
- HOJWFVSHZMXLAP-UHFFFAOYSA-N 3-[benzyl(methyl)amino]-1-phenylpropan-1-ol Chemical compound C=1C=CC=CC=1CN(C)CCC(O)C1=CC=CC=C1 HOJWFVSHZMXLAP-UHFFFAOYSA-N 0.000 description 1
- YJWZCUHMWDKUES-UHFFFAOYSA-N 3-chloro-n,n-dimethyl-3-phenylpropan-1-amine Chemical compound CN(C)CCC(Cl)C1=CC=CC=C1 YJWZCUHMWDKUES-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- OWAQXCQNWNJICI-UHFFFAOYSA-N benzene;chloroform Chemical compound ClC(Cl)Cl.C1=CC=CC=C1 OWAQXCQNWNJICI-UHFFFAOYSA-N 0.000 description 1
- KYRWMKZDUPPEBD-UHFFFAOYSA-M benzyl-dimethyl-[3-phenyl-3-[4-(trifluoromethyl)phenoxy]propyl]azanium;chloride Chemical compound [Cl-].C=1C=CC=CC=1C[N+](C)(C)CCC(C=1C=CC=CC=1)OC1=CC=C(C(F)(F)F)C=C1 KYRWMKZDUPPEBD-UHFFFAOYSA-M 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 229960002464 fluoxetine Drugs 0.000 description 1
- -1 for example Substances 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- PHTQWCKDNZKARW-UHFFFAOYSA-N isoamylol Chemical compound CC(C)CCO PHTQWCKDNZKARW-UHFFFAOYSA-N 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
- QUFZVVNFYXEIAK-UHFFFAOYSA-N n,n-dimethyl-3-phenyl-3-[4-(trifluoromethyl)phenoxy]propan-1-amine Chemical compound C=1C=CC=CC=1C(CCN(C)C)OC1=CC=C(C(F)(F)F)C=C1 QUFZVVNFYXEIAK-UHFFFAOYSA-N 0.000 description 1
- PKFLCEJSNGQGBK-UHFFFAOYSA-N n-methyl-n-[(4-nitrophenyl)methyl]-3-phenyl-3-[4-(trifluoromethyl)phenoxy]propan-1-amine Chemical class C=1C=C([N+]([O-])=O)C=CC=1CN(C)CCC(C=1C=CC=CC=1)OC1=CC=C(C(F)(F)F)C=C1 PKFLCEJSNGQGBK-UHFFFAOYSA-N 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- AHWALFGBDFAJAI-UHFFFAOYSA-N phenyl carbonochloridate Chemical compound ClC(=O)OC1=CC=CC=C1 AHWALFGBDFAJAI-UHFFFAOYSA-N 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
Područje tehnike kojoj izum pripada
Int. klas. C07C 93/08, A61K 31/135
Izum se odnosi na N-alkil-, N-aril- i N-alkoksikarbonil derivate N-metil-3-(p-trifluorometilfenoksi)-3-fenilpropilamina kao i na postupak za njihovu pripravu.
Najsličniji poznati spojevi su N,N-dimetil- i alkil N-karboksilat derivati N-metil-3-(p-trifluorometilfenoksi) 3-fenilpropilamina. N,N-dimetil derivat je pripravljen kondenzacijom N,N-dimetil-3-fenil-3-klorpropilamina i p-trifluorometilfenola [SAD pat. 4,018,895(1977)], a alkil N-karboksilat derivati su priređeni reakcijom alkil M-metil-3-fenil-3-metilsulfonil-oksipropilamin-N-karboksilata i p-trifluorometilfenola [Španjol. pat. 556 009(1986)]. N,N-dimetil i alkil N-metil-N-karboksilat derivati se koriste kao intermedijeri u sintezi farmakološki vrlo važnog N-metil-3-(p-trifluoro-metilfenoksi)-3-fenilpropilamina (fluoxetin).
Predmet ovog izuma je postupak priprave N-supstituiranih derivata N-metil-3-(p-trifluorometilfenoksi)-3-fenil propilamina opće formule I,
[image]
gdje radikal R ima značenje arilnog, alkilarilnog i alkilnog ostatka s C1 do C4 atoma, a n može biti 0 i 1.
Daljnji predmet ovog izuma su spojevi opće formule I, gdje radikal R ima značenje arilnog i alkilarilnog ostatka, a n ima prije navedeno značenje. Nađeno je da se spojevi opće formule I, gdje radikal R ima značenje benzilnog i p-nitrobenzilnog ostatka, a n 0, mogu lako i u visokom iskorištenju pripraviti kondenzacijom N-supstituiranih derivata N-metil-3-fenil-3-hidroksipropilamina opće formule II,
[image]
gdje radikal R ima značenje benzilnog i p-nitrobenzilnog ostatka, a n 0, i p-trifluorometilklorbenzena formule III,
[image]
u N,N-dimetilacetamidu uz natrijev hidrid na temperaturi 90-160°C. Dobiveni N-supstituirani derivati opće formule I, gdje radikal R ima značenje benzilnog i p-nitrobenzilnog ostatka, a n je 0 podvrgnu se reakciji s esterima klormravlje kiseline opće formule IV,
[image]
gdje radikal R ima prije navedeno značenje, u aprotičnom otapalu kao što su npr. metilenklorid, toluen, ksilen, na temperaturi 20-115°C. Uparavanjem organskog otapala nakon završene reakcije i pranja s vodom i kristalizacije ostatka iz pogodnog otapala kao što su npr. petroleter, niži alkoholi, ili kromatografije na stupcu silikagela, dobiju se spojevi opće formule I, gdje radikal R ima prije navedeno značenje, a n je 1. Također je nađeno da se reakcijom N.N-dimetil derivata i estera klormravlje kiseline kao glavni reakcijski proizvod katkada dobiju vrlo stabilne kvarterne amonijeve soli, a ne odgovarajući N-metil-N-alkoksikarbonil derivati (M. Matzner, R. P. Kurkjy and R. J. Cotter, Chem. Rew., 64 (1964) 645; B. J. Calvert and J. D. Hobson, J. Chem. Soc., 1965, 2723).
Prema ovom izumu proizlazi da su N-benzil- i N-p-nitrobenzil-N--metil-3-(p-trifluorometilfenoksi)-3-fenilpropilamini mnogo pogodniji supstrati za pripravu N-metil-N-alkoksikarbonil derivata, nego odgovarajući N,N-dimetil derivat.
Primjer 1
N-benzil-N-metil-3-(p-trifluorometilfenoksi)-3-fenilpropilamin
Otopina N-benzil-N-metil-3-fenil-3-hidroksipropilamina (2,55 g, 0,01 mol) u N.N-dimetilacetamidu (8 ml) se dokapa u suspenziju natrij hidrida (0,43 g 60%-tna disperzija u ulju, 0,011 mol) u N.N-dimetilacetamidu (6 ml) i grije 5-10 min na 70-75°C. U nastalu smjesu se doda p-trifluorometilklorbenzen (2,1 g, 0,0115 mol) i dobivena reakcijska smjesa se grije 6 sati na temperaturi 130-135°C, zatim upari u vakuumu i ostatak otopi u toluenu (12 ml). Otopina se opere vodom (4x5 ml), organski sloj profiltrira, zatim se u njega dokapa uz miješanje 2N kloridna kiselina (12 ml) i hladi 2 do 3 sata na 5-10°C. Izlučeni bijeli kristali se odsišu i prvo operu vodom (10 ml), a zatim s toluenom (10 ml). Dobije se 3,92 g proizvoda u obliku hidroklorida t.t. 155-156°C. Dobijeni hidroklorid se miješa u 1N natrij hidroksidu (20 ml) 10 min. na temperaturi 60-70°C, ekstrahira s toluenom (25 ml), organski sloj opere vodom (4 x 10 ml), profiltrira i upari u vakuumu. Dobije se 3,59 g (90,0 %) N-benzil-N-metil-3-(p-trifluorometilfenoksi)-3-fenilpropilamina t.t. 42-44°C.
IR (KBr): 2970w, 1620m, 1520m, 1460m, 1330vs, 1250s, 1210vs, 1175s, 1070s,835m,700s,cm-1;
300 MHz 1H NMR (CDCl3) 5: 1,96-2,05 (2 H, m, CH2), 2,22(3 H, s, NMe), 2,39-2,48 i 2,57-2,64 (2 H, m, CH2), 3,47 i 3,51 (2 H, 2d, J 12 Hz, CH2Ph), 5,32 (1 H, dd, CH), 6,86 (2 H, d, J 8,6 Hz, arom.), 7,22-7,30 (10 H, m, 2 C6H5),
7,41 (2 H, d, J 8,6 Hz, arom.);
Anal. C24H24F3NO (399,46)
izračunato: C 72,16; H 6,06; N 3,51 %
nađeno: C 72,18; H 6,34; N 3,54 %
Primjer 2
Metil N-metil-3-(p-trifluorometilfenoksi)-3-fenilpropilamin-N-karboksilat
Otopina N-benzil-N-metil-3-(p-trifluorometilfenoksi)-3-fenilpropil-amina (4,0 g, 0,01 mol) i metil klorformijata (1,45 g 98%-tni, 0,015 mol) u toluenu (50 ml) grije se 4 sata u zataljenoj cjevčici na temperaturi 110-115°C. Nakon hlađenja reakcijska otopina se opere prvo 0,1N kloridnom kiselinom (4 x 10 ml), a zatim 0,1N natrij hidroksidom. (4 x 10 ml). Na kraju se organski sloj opere vodom (4 x 10 ml), upari u vakuumu i ostatak prekristalizira iz petroletera (12 ml). Dobije se 3,3 g 90%) metil N-metil-3-(p-trifluorometilfenoksi)-3-fenilpropilamin-N-karboksilata t.t. 72-74°C.
IR (KBr): 2960w, 1710vs, 1620s, 1490m, 1410m, 1375m, 1340vs, 1275vs, 1165vs, 1070s,845vs,700s cm-1;
300 MHz 1H NMR (CDCl3)6: 2,09-2,10 (2 H, br, CH2), 2,94 (3 H, s, NMe), 3,48-3,65 (5 H, br, CO2Me i CH2), 5,13-5,19 (1 H, br, CH), 6,9 (2 H, d, J 8,6 Hz, arom.), 7,25-7,35 (5 H, m, C6H5), 7,4 (2 H, d, J 8,6 Hz, arom.);
Anal: C19H20F3NO3 (367,36)
izračunato: C 62,11; H 5,49; N 3,81 %
nađeno: C 62,33; H 5,63; N 3,79 %
Primjer 3
Fenil N-metil-3-(p-trifluorometilfenoksi)-3-fenilpropilamin-N-karboksilat
Otopina N-benzil-N-metil-3-(p-trifluorometilfenoksi)-3-fenilpropilamina (4,0 g, 0,01 mol) i fenil klorformijata (1,76 g 98%-tni, 0,011 mol) u metilenkloridu (50 ml) miješa se 3 sata na sobnoj temperaturi i reakcijska otopina se zatim obradi analogno postupku opisanom u primjeru 2. Dobije se 3,71 g (86,5 %, i-propanol) čistog fenil N-metil-3-(p-trifluorometilfenoksi)-3-fenilpropil-amin-N-karboksilata t.t. 83-84°C.
IR(KBr): 2940w, 1715vs, 1620s, 1580m, 1410vs, 1340vs, 1260vs, 1190vs, 1110vs, 1050vs, 947s, 835s, 700s cm-1;
300 MHz 1H NMR (CDCl3)5: 2,16-2,35 (2 H. m, CH2), 3,02 i 3.09 (3 H, 2s, NMe), 3,49-3.69 i 3,78-3,85 (2 H, 2m, CH2), 5.23-5,26 (1 H, br. CH), 6,84 (2 H, d, J 10,5 Hz, arom.), 6,90-7.35 (10 H, m, 2 C6H5), 7,42 (2 H, d, J 10,5 Hz, arom.);
Anal. C24H22F3NO3 (429,42)
izračunato: C 67,12; H 5,16; N 3,26 %
nađeno: C 67,38; H 5,36; N 3,38 %
Primjer 4
p-Nitrofenil N-metil-3-(p-trifluorometilfenoksi)-3-fenilpropilamin-N-karboksilat
Analogno postupku opisanom u primjem 2 iz N-benzil-N-metil-3-(p-trifluorometilfenoksi)-3-fenilpropilamina (4,0 g, 0,01 mol) i p-nitrofenil klorformijata (2,37 g 97%-tni, 0,011 mol) u metilenkloridu (50 ml) dobije se 4,36 g (92 %, i-amilni alkohol) p-nitrofenil N-metil-3-(p-trifluorometilfenoksi)-3-fenilpropilamm-N-karboksilata t.t. 96-97°C.
IR (KBr): 2970w, 1720vs, 1620m, 1520s, 1410m, 1350s, 1320s, 1260s, 1210s, 1160s, 1110s, 840s, 750m cm-1;
300 MHz 1H NMR (CDCl3)8: 2,14-2,35 (2 H, br, CH2), 3,05 i 3,11 (3 H, 2s, NMe), 3,49-3,60, 364-3,74 i 3,82-3,92 (2 H, 3m, CH2), 5,21-5,29 (1 H, m, CH), 6,86 (2 H, d, J 8,7 Hz, arom), 6,91 i 6,98 (2 H, 2d, J 9 i 9 Hz, arom), 7,14-7,39 (5 H, m, C6H5), 7,43 (2 H. d. J 8,7 Hz, arom) ,8,12 i 8,19 (2 H, 2d, J 9 i 9 Hz, arom);
Anal: C24H21F3N2O5 (474,42)
izračunato: C 60,76; H 4,46; N 5,91 %
nađeno: C 61,03; H 4,37; N 6,20 %
Primjer 5
Benzil N-metil-3-(p-trifluorometilfenoksi)-3-fenilpropilamin-N-karboksilat
Otopina N-metil-N-p-nitrobenzil-3-(p-trifluorometilfenoksi)-3-fenilpropil amina (4,43 g, 0,01 mol) i benzil klorformijata (1,98 g 95%-tni, 0,011 mol) u metilenkloridu (50 ml) grije se 5 sati na temperaturi ključanja otopine i zatim obradi analogno postupku opisanom u primjeru 2. Ostatak nakon uparavanja toluenskog sloja se kromatografira na stupcu silikagela uz eluiranje sa smjesom otapala kloroform-benzen (1:1). Izolira se 3,77 g (85 %, Rf=0,47) benzil N-metil-3-(p-trifluorometilfenoksi)-3-fenilpropilamin-N-karboksilata u obliku ulja.
IR (KBr) : 2965w, 1710vs, 1620s, 1460m, 1410m, 1335vs, 1255vs, 1165vs, 1115vs, 1075s, 840s, 700s cm-1
300 MHz 1H NMR (CDCl3): 2,06-2,22 (2 H, br, CH2), 2,93 (3 H, s, NMe), 3,44-3,57 (2 H, br, CH2), 4,86-5,19 (3 H, br, CH i CO2CH2Ph), 6,80-7,14 (14 H, m, arom);
Anal. C25H24F3NO3 (443,45)
izračunato: C 67,70; H 5,46; N3,16%
nađeno: C 67,45; H 5,68; N 3,05 %
Primjer 6
N,N-dimetil-N-benzil-3-(p-trifluorometilfenoksi)-3-fenilpropilamonijev klorid
Otopina N,N-dimetil-3-(p-trifluorometilfenoksi)-3-fenilpropilamina (3,23 g, 0,01 mol) i benzil klorformijata (1,98 g 98%-tni, 0,011 mol) u toluenu (20 ml) grije se 4 sata na temperaturi ključanja smjese i zatim hladi 15 sati na 0-5 °C. Izlučeni kristali se odsišu i prekristaliziraju iz toluena (20 ml). Dobije se 3,46 g (77 %) N,N-dimetil-N-benzil-3-(p-trifluoro-metilfenoksi)-3-fenilpropilamomjeva klorida t.t. 154-155 °C.
IR (KBr): 3020w, 2980w, 1620s, 1525s, 1340vs, 1255vs, 1160vs, 1025vs, 1070vs, 835vs, 735s, 705s cm-1;
300 MHz 1H NMR (CDCl3):5 2,70-2,81 (2 H, m, CH2), 3,56 (6 H, s, NMe2), 3,91-3,97 i 4,18-4,24 (2 H, 2m, CH2), 5,16 i 5,27 (2 H, 2d, J 12,6 i 12,6 Hz, CH2Ph), 5,73 (1 H, dd, CH, 7,13-7,83 (14 H, m, arom);
Anal. C25H27ClF3NO (449,93)
izračunato: C 66,73; H 6,03; N 3,11; Cl 7,88 %
nađeno: C 67,02; H 6,15; N 3,06; Cl 8,08 %
Claims (8)
1. Postupak za pripravu N-supstituiranih derivata N-metil-3-(p-triflorometilfenoksi)-3-fenilpropilamina opće formule I
[image]
gdje kad je n=0 R ima značenje benzilne ili p-nitrobenzilne skupine, a kad je n=1 R predstavlja arilnu, alkilarilnu ili alkilnu skupinu s C1-C4 atoma, naznačen time, da se kondenzacijom N-supstituiranih derivata N-metil-3-fenil-3-hidroksipropilamina opće formule II,
[image]
gdje radikal R ima značenje benzilnog i p-nitrobenzilnog ostatka, a n 0 i p-trifluorometilklor benzena formule III,
[image]
priprave N-supstituirani derivati N-metil-3-(p-trifluorometilfenoksi)-3-fenilpropilamina opće formule I, gdje radikali R ima značenje bezilnog i p-nitrobenzilnog ostatka, a n je 0, koji se zatim reakcijom s esterima klormravlje kiseline opće formule IV,
ClCOOR IV
gdje radikal R ima prije navedeno značenje, prevede u spoj opće formule I, gdje radikal R ima prije navedeno značenje, a n je 1.
2. N-supstituirani derivati N-metil-3-(p-trifluorometilfenoksi)-3-fenil-propilamina opće formule I, naznačeni time, da kadje n=0, R predstavlja benzil ili p-nitrobenzil, a kad je n=1, R predstavlja aril ili alkil.
3. Spoj prema zahtjevu 2, naznačen time, da je radikal R benzil, a n je 0.
4. Spoj prema zahtjevu 2, naznačen time, da je radikal R p-nitrobenzil, a n je 0.
5. Spoj prema zahtjevu 2, naznačen time, da je radikal R fenil, a n je 1.
6. Spoj prema zahtjevu 2, naznačen time, da je radikal R p-nitrofenil, a n je 1.
7. Spoj prema zahtjevu 2, naznačen time, da je radikal R benzil, a n je 1.
8. Spoj prema zahtjevu 2, naznačen time, da je radikal R p-nitrobenzil, a n je 1.
Priority Applications (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HR930129A HRP930129B1 (en) | 1993-02-05 | 1993-02-05 | N-substituted derivatives of n-methyl-3-(p-trifluoromethylphenoxy)-3-phenylpropylamine and procedure for their preparation |
| US08/145,141 US5618968A (en) | 1993-02-05 | 1993-11-03 | N-substituted derivatives of N-methyl-3-(p-trifluoromethylphenoxy)-3-phenylpropylamine and the procedure for their preparation |
| SI9400049A SI9400049B (en) | 1993-02-05 | 1994-02-01 | N-substituted derivatives of n-methyl-3-(p-trifluoromethyl- phenoxy)-3-phenylpropylamine and process for their preparation |
| EP94101743A EP0617006B1 (en) | 1993-02-05 | 1994-02-04 | N-Substituted derivatives of N-methyl-3-(p-trifluoromethylphenoxy)-3-phenylpropylamine and procedure for their preparation |
| AT94101743T ATE165810T1 (de) | 1993-02-05 | 1994-02-04 | N-substituierte derivate des n-methyl-3-(p- trifluormethylphenoxy)-3-phenylpropylamins und verfahren zu deren herstellung |
| DE69410005T DE69410005T2 (de) | 1993-02-05 | 1994-02-04 | N-Substituierte Derivate des N-Methyl-3-(p-trifluormethylphenoxy)-3-phenylpropylamins und Verfahren zu deren Herstellung |
| ES94101743T ES2118988T3 (es) | 1993-02-05 | 1994-02-04 | Derivados n-sustituidos de n-metil-3-(p-trifluoro-metil-fenoxi)-3-fenil-propil-amina y el procedimiento para su preparacion. |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HR930129A HRP930129B1 (en) | 1993-02-05 | 1993-02-05 | N-substituted derivatives of n-methyl-3-(p-trifluoromethylphenoxy)-3-phenylpropylamine and procedure for their preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| HRP930129A2 true HRP930129A2 (en) | 1994-12-31 |
| HRP930129B1 HRP930129B1 (en) | 2000-12-31 |
Family
ID=10945882
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HR930129A HRP930129B1 (en) | 1993-02-05 | 1993-02-05 | N-substituted derivatives of n-methyl-3-(p-trifluoromethylphenoxy)-3-phenylpropylamine and procedure for their preparation |
Country Status (1)
| Country | Link |
|---|---|
| HR (1) | HRP930129B1 (hr) |
-
1993
- 1993-02-05 HR HR930129A patent/HRP930129B1/xx not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| HRP930129B1 (en) | 2000-12-31 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR100555970B1 (ko) | 2-아미노-1,3-프로판디올유도체의 제조방법 | |
| GB1575709A (en) | 1,1-cycloalkyldiacetic acid imide derivatives and their use for preparing 1-aminomethyl-1-cycloalkylacetic acids | |
| SU651704A3 (ru) | Способ получени производных дибензоциклогептена, рацемических или оптически активных, или их солей | |
| JP2018518489A (ja) | アプレミラスト及びその中間体の調製方法 | |
| JP2818763B2 (ja) | Ｎ−（ヒドロキシ）アラルキルフェニルエタノールアミン類のｏ−アルキル化された化合物 | |
| EP0617006B1 (en) | N-Substituted derivatives of N-methyl-3-(p-trifluoromethylphenoxy)-3-phenylpropylamine and procedure for their preparation | |
| CN101939289A (zh) | 用于制备伏立诺他的新方法 | |
| KR100352047B1 (ko) | 사이클로프로판유도체및이의제조방법 | |
| HRP930129A2 (en) | N-subutituted derivatives of n-methyl-3-(p-trifluoromethylphenoxy) -3-phenylpropilamine and the process for the preparation thereof | |
| JPH02188570A (ja) | ハロゲン置換キノリン誘導体の製造法 | |
| US4416827A (en) | Process for the resolution of the racemate (1RS,2SR)-2-amino-1-phenyl-propan-1-ol | |
| CZ282068B6 (cs) | 3-Methoxy-4-[1-methyl-5-(2-methyl-4,4,4-trifluorbutylkarbamoyl)indol-3-ylmethyl]-N-(2-methylfenylsulfonyl)benzamid, jeho farmaceuticky přijatelná sůl, způsob jejich přípravy a farmaceutické prostředky tyto látky obsahující | |
| SK285681B6 (sk) | Spôsob chlórmetylácie tiofénu | |
| JP4682204B2 (ja) | ４，５−ジアミノシキミ酸の製造方法 | |
| US4091029A (en) | N-pentafluoropropionyl and n-heptafluorobutyryl proline | |
| GB2106516A (en) | Anthranilic acid esters | |
| US2540307A (en) | 3, 4-diethoxymandelic acid and process for preparing same | |
| GB2056988A (en) | Oxime Derivatives of 2-(2- tritylamino-thiazolyl)-acetic Acid and Alkyl Esters Thereof | |
| EP0095091B1 (en) | Process for the preparation of dihydrolysergic acid esters | |
| JP3632979B6 (ja) | ２―アミノマロン酸誘導体及び２―アミノ―１，３―プロパンジオール誘導体の製造方法 | |
| GB2134521A (en) | Improvements in or relating to the synthesis of nizatidine | |
| Brown et al. | Synthesis of chiral polyfunctionalised cyclopentanes from the Diels–Alder adduct of furan and maleic anhydride | |
| SK8893A3 (en) | Process for preparing 2-carboxy-3-[2-(dimethylamino)-ethyl]-n- -methyl-1h-indole-5-methanesulfonamide and lower alkyl esters thereof | |
| JPH0338265B2 (hr) | ||
| KR950006149B1 (ko) | 신규 n-(2-할로알카노일옥시)석신이미드 유도체 및 그 제조방법 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A1OB | Publication of a patent application | ||
| AIPI | Request for the grant of a patent on the basis of a substantive examination of a patent application | ||
| PNAN | Change of the applicant name, address/residence |
Owner name: PLIVA, FARMACEUTSKA, KEMIJSKA, PREHRAMBENA I KOZME |
|
| B1PR | Patent granted | ||
| ODRP | Renewal fee for the maintenance of a patent |
Payment date: 20031210 Year of fee payment: 12 |
|
| PBON | Lapse due to non-payment of renewal fee |
Effective date: 20050206 |