| PATENT NUMBER | This data is not available for free |
| PATENT GRANT DATE | February 2, 1982 |
| PATENT TITLE |
Aryloxyphenylpropylamines |
| PATENT ABSTRACT | 3-Aryloxy-3-phenylpropylamines and acid additions salts thereof, useful as psychotropic agents, particularly as anti-depressants |
| PATENT INVENTORS | This data is not available for free |
| PATENT ASSIGNEE | This data is not available for free |
| PATENT FILE DATE | January 10, 1974 |
| PATENT REFERENCES CITED | Yoshika et al., "Pharm. Soc. of Japan", vol 93, pp. 508-528 (1973). |
| PATENT CLAIMS |
-------------------------------------------------------------------------------- We claim: 1. A compound of the formula ##STR7## wherein each R' is independently H or CH.sub.3 and R is m- or p-chlorophenyl, o-, m-, or p-methoxyphenyl, phenyl, o- or m-fluorophenyl, o- or p-tolyl, 2,4-difluorophenyl or p-trifluoromethylphenyl and acid addition salts formed with pharmaceutically-acceptable acids. 2. A compound according to claim 1, said compound being N-methyl 3-(o-tolyloxy)-3-phenylpropylamine and pharmaceutically-acceptable acid addition salts thereof. 3. A compound according to claim 2, said compond being N-methyl 3-(o-tolyloxy)-3-phenylpropylamine hydrochloride. 4. A compound according to claim 1, said compound being N-methyl 3-(p-trifluoromethylphenoxy)-3-phenylpropylamine, and pharmaceutically-acceptable acid addition salts thereof formed with non-toxic acids. 5. A compound according to claim 4, said compound being N-methyl 3-(p-trifluoromethylphenoxy)-3-phenylpropylamine hydrochloride. 6. A compound according to claim 1, said compound being N-methyl 3-(o-methoxyphenoxy)-3-phenylpropylamine, and pharmaceutically-acceptable acid addition salts thereof formed with non-toxic acids. 7. A compound according to claim 1, said compound being N-methyl 3-(o-methoxyphenoxy)-3-phenylpropylamine hydrochloride. 8. A compound according to claim 1, said compound being N-methyl 3-(2,4-difluorophenoxy)-3-phenylpropylamine. 9. A compound according to claim 8, said compound being N-methyl 3-(m-fluorophenoxy)-3-phenylpropylamine oxalate. -------------------------------------------------------------------------------- |
| PATENT DESCRIPTION |
BACKGROUND OF THE INVENTION Tertiary 2-phenoxy-2-phenylethylamines constitute the subject matter of U.S. Pat. No. 3,106,564. The compounds are said to be useful pharmacological agents exhibiting activity on the central nervous system including useful application as analeptic agents without significant effect on respiration. The compounds are also said to have a high order of activity as antihistaminic and anticholinergic agents. Several tertiary 3-phenoxy-3-phenylpropylamines and quaternary ammonium compounds are disclosed in J. Pharmaceutical Society, Japan, 93, 508-519, 1144-53, 1154-61 (1973). The compounds are said to be mydriatic agents. Secondary and primary 3-aryloxy-3-phenylpropylamines have not hitherto been known. SUMMARY OF THE INVENTION This invention provides 3-aryloxy-3-phenylpropylamines of the formula: ##STR1## wherein each R' is independently hydrogen or methyl; wherein R is naphthyl or ##STR2## wherein R" and R'" are halo, trifluoromethyl, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.3 alkoxy or C.sub.3 -C.sub.4 alkenyl; and wherein n and m are 0, 1 or 2; and acid addition salts thereof formed with pharmaceutically-acceptable acids. In the above formula when R is naphthyl, it can be either .alpha.-naphthyl of .beta.-naphthyl. R" and R'" when they are halo, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.3 alkyloxy or C.sub.3 -C.sub.4 alkenyl represent, illustratively, the following atoms or groups: fluoro, chloro, bromo, iodo, methyl, ethyl, isopropyl, n-propyl, n-butyl, isobutyl, sec.-butyl, t-butyl, methoxy, ethoxy, n-propoxy, isopropoxy, allyl, methallyl, crotyl and the like. R thus can represent o, m and p-trifluoromethylphenyl, o, m and p-chlorophenyl, o,m and p-bromophenyl, o,m and p-fluorophenyl, o,m and p-tolyl, xylyl including all position isomers, o,m and p-anisyl, o,m and p-allylphenyl, o,m and p-methylallylphenyl, o,m and p-phenetolyl(ethoxyphenyl), 2,4-dichlorophenyl, 3,5-difluorophenyl, 2-methoxy-4-chlorophenyl, 2-methyl-4-chlorophenyl, 2-ethyl-4-bromophenyl, 2,4,6-trimethylphenyl, 2-fluoro-4-trifluoromethylphenyl, 2,4,6-trichlorophenyl, 2,4,5-trichlorophenyl, and the like. Compounds illustrative of the scope of this invention include the following: 3-(p-isopropoxyphenoxy)-3-phenylpropylamine methanesulfonate N,N-dimethyl 3-(3',4'-dimethoxyphenoxy)-3-phenylpropylamine p-hydroxybenzoate N,N-dimethyl 3-(.alpha.-naphthoxy)-3-phenylpropylamine bromide N,N-dimethyl 3-(.beta.-naphthoxy)-3-phenyl-1-methylpropylamine iodide 3-(2'-methyl-4',5'-dichlorophenoxy)-3-phenylpropylamine nitrate 3-(p-t-butylphenoxy)-3-phenylpropylamine glutarate N-methyl 3-(2'-chloro-p-tolyloxy)-3-phenyl-1-methylpropylamine lactate 3-(2',4'-dichlorophenoxy)-3-phenyl-2-methylpropylamine citrate N,N-dimethyl 3-(m-anisyloxy)-3-phenyl-1-methylpropylamine maleate N-methyl 3-(p-tolyloxy)-3-phenylpropylamine sulfate N,N-dimethyl 3-(2',4'-difluorophenoxy)-3-phenylpropylamine 2,4-dinitrobenzoate 3-(o-ethylphenoxy)-3-phenylpropylamine dihydrogen phosphate N-methyl 3-(2'-chloro-4'-isopropylphenoxy)-3-phenyl-2-methylpropylamine maleate N,N-dimethyl 3-(2'-alkyl-4'-fluorophenoxy)-3-phenyl-propylamine succinate N,N-dimethyl 3-(o-isopropoxyphenoxy)-3-phenyl-propylamine phenylacetate N,N-dimethyl 3-(o-bromophenoxy)-3-phenyl-propylamine .beta.-phenylpropionate N-methyl 3-(p-iodophenoxy)-3-phenyl-propylamine propiolate N-methyl 3-(3-n-propylphenoxy)-3-phenyl-propylamine decanoate Also included within the scope of this invention are the pharmaceutically-acceptable salts of the amine bases represented by the above formula formed with non-toxic acids. These acid addition salts include salts derived from inorganic acids such as: hydrochloric acid, nitric acid, phosphoric acid, sulfuric acid, hydrobromic acid, hydriodic acid, nitrous acid, phosphorous acid and the like, as well as salts of non-toxic organic acids including aliphatic mono and dicarboxylates, phenyl-substituted alkanoates, hydroxy alkanoates and alkanedioates, aromatic acids, aliphatic and aromatic sulfonic acids etc. Such pharmaceutically-acceptable salts thus include: sulfate, pyrosulfate, bisulfate, sulfite, bisulfite, nitrate, phosphate, monohydrogenphosphate, dihydrogenphosphate, metaphosphate, pyrophosphate, chloride, bromide, iodide, fluoride, acetate, propionate, decanoate, caprylate, acrylate, formate, isobutyrate, caprate, heptanoate, propiolate, oxalate, malonate, succinate, suberate, sebacate, fumarate, maleate, butyne-1,4-dioate, hexyne-1,6-dioate, benzoate, chlorobenzoate, methylbenzoate, dinitrobenzoate, hydroxybenzoate, methoxybenzoate, phthalate, terephthalate, benzenesulfonates, toluenesulfonate, chlorobenzenesulfonate, xylenesulfonate, phenylacetate, phenylpropionate, phenylbutyrate, citrate, lactate, .beta.-hydroxybutyrate, glycollate, malate, tartrate, methanesulfonate, propanesulfonates, naphthalene-1-sulfonate, naphthalene-2-sulfonate, mandelate and the like salts. The compounds of this invention in the form of their free bases are high boiling oils, but white crystalline solids in the form of their acid addition salts. The compounds can be prepared in several ways. A particularly useful procedure for preparing compounds represented by the above formula (in which both R' groups attached to the nitrogen are methyl) involves the reduction of .beta.-dimethylaminopropiophenone produced by a Mannich reaction to yield N,N-dimethyl 3-phenyl-3-hydroxypropylamine. Replacement of the hydroxyl group with a halogen, such as chlorine, yields the corresponding N,N-dimethyl 3-phenyl-3-chloropropylamine. Reaction of this chloro compound with a suitably substituted phenol, as for example o-methoxyphenol (guiacol), produces a compound of this invention in which both R' groups are methyl. Treatment of the N,N-dimethyl compound with cyanogenbromide serves to replace one N-methyl group with a cyano group. Hydrolysis of the resulting compound with base yields a compound of this invention in which only one R' group on the nitrogen is methyl. For example, treatment of N,N-dimethyl 3-(o-anisyloxy)-3-phenylpropylamine with cyanogen bromide followed by alkaline hydrolysis of the N-cyano compound yields directly N-methyl 3-(o-anisyloxy)-3 -phenylpropylamine [N-methyl 3-(o-methoxy phenoxy)-3-phenylpropylamine]. An alternate preparation of the compounds of this invention in which only one of the R' groups attached to the nitrogen is methyl is carried out as follows: 3-Chloropropylbenzene is reacted with a positive halogenating agent such N-bromosuccinimide to yield the corresponding 3-chloro-1-bromopropylbenzene. Selective replacement of the bromo atom with the sodium salt of a phenol, as for example, the sodium salt of o-methoxyphenol (guiacol) yields a 3-chloro-1-(1-methoxyphenoxy)-propylbenzene [also named as 3-chloro-1-(o-anisyloxy)propylbenzene]. Reaction of the 3-chloro derivative thus produced with methylamine yields the desired N-methyl 3-(o-anisyloxy)-3-phenylpropylamine. Compounds in which both R' groups attached to the nitrogen in the above formula are hydrogen can be prepared from an intermediate produced in the previous preparation of the N-methyl compounds such as, for illustrative purposes, 3-chloro-1-(o-anisyloxy)-propylbenzene prepared by the reaction of 3-chloro-1-bromobenzene and sodium guiacol. This chloro compound is reacted with sodium azide to give the corresponding 3-azido-1-(o-anisyloxy)-propylbenzene. Reduction of the azide group with a metallo-organic reducing agent such as sodium borohydride yields the desired primary amine. Alternatively, the chloro compound can be reacted directly with a large excess of ammonia in a high pressure reactor to give the primary amine. Compounds in which the R' group on the carbon atom alpha to the nitrogen is methyl can be prepared by reacting phenyl 2'-propenyl ketone with dimethylamine [See J. Am. Chem. Soc., 75, 4460 (1953)]. The resulting 3-dimethylaminobutyrophenone is reduced to yield the N,N-dimethyl 3-hydroxy-1-methyl-3-phenylpropylamine. Replacement of the hydroxyl with chlorine followed by reaction of the chloro-compound with the sodium salt of a suitably substituted phenol yields the N,N-dimethyl derivatives of this invention bearing an alpha methyl group on the propylamine backbone of the molecule. Production of the corresponding N-methyl derivative can be accomplished by the aforementioned reaction sequence utilizing cyanogen bromide. The N-methyl derivative can in turn be converted to the corresponding primary amine (in which both R' groups on the nitrogen are hydrogen) by oxidation in neutral permanganate according to the procedure of Booher and Pohland, Ser. No. 317,969, filed Dec. 26, 1972. Compounds in which the R' group attached to the .beta.-carbon atom is methyl are prepared by a Mannich reaction involving propiophenone, formaldehyde and dimethylamine. The resulting ketone, a .alpha.-methyl-.beta.-dimethylaminopropiophenone, is subjected to the same reduction procedure as before to yield a hydroxy compound. Replacement of the hydroxyl with chlorine followed by reaction of the chloro compound with the sodium salt of a phenol yields a dimethyl amine compound of this invention. Conversion of the dimethylamine to the corresponding monomethyl and primary amines is carried out as before. Those compounds in which the R' group attached to either the .alpha. or .beta.-carbon is methyl have two asymmetric carbon atoms, the carbon carrying the R' methyl and the .gamma.-carbon carrying the phenoxy and phenyl groups. Thus, such compounds exist in four diastereomeric forms occurring as two racemic pairs, the less soluble pair being designated .alpha.-dl form and the more soluble the .beta.-dl form. Each racemate can be resolved into its individual d and l isomers by methods well known in the art, particularly, by forming salts with optically active acids and separating the salts by crystallization. This invention is further illustrated by the following specific examples: EXAMPLE 1 Preparation of N-methyl 3-(p-trifluoromethylphenoxy)-3-phenylpropylamine and of N,N-dimethyl 3-(p-trifluoromethylphenoxy)-3-phenylpropylamine. About 600 g. of .beta.-dimethylaminopropiophenone hydrochloride were converted to the corresponding free base by the action of 1.5 N aqueous sodium hydroxide. The liberated free base was taken up in ether, the ether layer separated and dried, and the ether removed therefrom in vacuo. The residual oil comprising .beta.-dimethylaminopropiophenone was dissolved in two liters of tetrahydrofuran, and the resulting solution added in dropwise fashion with stirring to a solution of four moles of diborane in four liters of tetrahydrofuran. The reaction mixture was stirred overnight at room temperature. An additional mole of diborane in one liter of tetrahydrofuran was added, and the reaction mixture stirred again overnight at room temperature. Next, two liters of aqueous hydrochloric acid were added to decompose any excess diborane present. The tetrahydrofuran was removed by evaporation. The acidic solution was extracted twice with one liter portions of benzene, and the benzene extracts were discarded. The acidic solution was then made basic with an excess of 5 N aqueous sodium hydroxide. The basic solution was extracted three times with two liter portions of benzene. The benzene extracts were separated and combined, and the combined extracts washed with a saturated aqueous sodium chloride and then dried. Evaporation of the solvent in vacuo yields 442 g. of N,N-dimethyl 3-phenyl-3-hydroxypropylamine. A solution containing 442 g. of N,N,-dimethyl 3-phenyl-3-hydroxypropylamine in 5 l. of chloroform was saturated with dry gaseous hydrogen chloride. 400 ml. of thionyl chloride were then added to the chloroform solution at a rate sufficient to maintain reflux. The solution was refluxed an additional 5 hours. Evaporation of the chloroform and other volatile constituents in vacuo yielded N,N-dimethyl 3-phenyl-3-chloropropylamine hydrochloride which was collected by filtration, and the filter cake washed twice with 1500 ml. portions of acetone. The washed crystals weighed about 500 g. and melted at 181.degree.-3.degree. C. with decomposition. An additional 30 g. of compound were obtained from the acetone wash by standard crystallization procedures. The structure of the above compound was verified by NMR and titration. A solution of 50 g. p-trifluoromethylphenol, 12 g. of solid sodium hyroxide and 400 ml. of methanol was placed in a one liter round-bottom flask equipped with magnetic stirrer, condenser and drying tube. The reaction mixture was stirred until the sodium hydroxide had dissolved. Next, 29.8 g. of N,N-dimethyl 3-phenyl-3-chloropropylamine hydrochloride were added. The resulting reaction mixture was refluxed for about 5 days and then cooled. The methanol was then removed by evaporation, and the resulting residue taken up in a mixture of ether and 5 N aqueous sodium hydroxide. The ether layer was separated and washed twice with 5 N aqueous sodium hydroxide and three times with water. The ether layer was dried, and the ether removed by evaporation in vacuo to yield as a residue N,N-dimethyl 3-(p-trifluoromethylphenoxy)-3-phenylpropylamine. The free base was converted to the corresponding oxalate salt by dissolving 32 g. of the amine in ethyl acetate to which was added a solution of 9 g. of oxalic acid also in ethyl acetate. N,N-dimethyl-3-p-trifluoromethylphenoxy-3-phenylpropylamine oxalate thus formed melted at 117.degree.-119.degree. C. with decomposition after recrystallization from ethyl acetate. Analysis calc.: C, 58.11; H, 3.36; N, 3.39; F, 13.79; Found: C, 58.19; H, 3.49; N, 3.59; F, 13.85. A solution containing 8.1 g. of cyanogen bromide in 500 ml. benzene and 50 ml. of toluene was placed in a one liter three-neck round-bottom flask equipped with thermometer, addition funnel, drying tube and inlet tube for nitrogen. The solution was cooled to about 5.degree. C. with stirring, and nitrogen gas was bubbled thru the solution. Next, a solution of 12.146 g. of N,N-dimethyl 3-(p-trifluoromethylphenoxy)-3-phenylpropylamine dissolved in 40 ml. of benzene was added in dropwise fashion. The temperature of the reaction mixture was allowed to rise slowly to room temperature, at which temperature stirring was continued overnight while still maintaining a nitrogen atmosphere. 100 ml. of benzene were added. The reaction mixture was washed twice with water, once with 2 N aqueous sulfuric acid and then with water until neutral. The organic layer was dried, and the solvents removed therefrom by evaporation in vacuo to yield about 9.5 g. of an oil comprising N-methyl-N-cyano 3-(p-trifluoromethylphenoxy)-3-phenylpropylamine. A solution of 100 g. potassium hydroxide, 85 ml. water, 400 ml. ethylene glycol and 9.50 g. of N-methyl-N-cyano 3-(p-trifluoromethylphenoxy)-3-phenylpropylamine was prepared in a one liter three-neck, round-bottom flask equipped with magnetic stirrer and condenser. The reaction mixture was heated to refluxing temperature (130.degree. C.) for 20 hours, and was then cooled. 500 ml. of water were added. The reaction mixture was extracted with three 500 ml. portions of ether. The ether extracts were combined, and the combined extracts washed with water. The water wash was discarded. The ether solution was next contacted with 2 N aqueous hydrochloric acid. The acidic aqueous layer was separated. A second aqueous acidic extract with 2 N hydrochloric acid was made followed by three aqueous extracts and an extract with saturated aqueous sodium chloride. The aqueous layers were all combined and made basic with 5 N aqueous sodium hydroxide. N-methyl 3-(p-trifluoromethylphenoxy)-3-phenylpropylamine, formed in the above reaction, was insoluble in the basic solution and separated. The amine was extracted into ether. Two further ether extractions were carried out. The ether extracts were combined, and the combined extracts washed with saturated aqueous sodium chloride and then dried. Evaporation of the ether in vacuo yielded about 6.3 g. of N-methyl 3-(p-trifluoromethylphenoxy)-3-phenylpropylamine. The amine free base was converted to the corresponding oxalate salt by the method set forth above. N-methyl 3-(p-trifluoromethylphenoxy) -3-phenylpropylamine oxalate thus prepared melted at 179.degree.-182.degree. C. with decomposition after recrystallization from an ethyl acetate-methanol solvent mixture. Analysis calc.: C, 57.14; H, 5.05; N, 3.51; F, 14.27; Found; C, 57.43; H, 5.30; N, 3.79; F, 14.24. The amine free base was also converted to the maleate salt. The following N,N-dimethyl or N-methyl 3-substituted phenoxy-3-phenylpropylamines were prepared by the above procedures. N,N-dimethyl 3-(o-chlorophenoxy)-3-phenylpropylamine maleate which melted at 88.degree.-90.degree. C. after recrystallization from an ethyl acetate-cyclohexane solvent mixture. Analysis calc.: C, 62.14; H, 5.96; N, 3.45; Cl, 8.73; Found; C, 61.94; H, 5.67; N, 3.68; Cl, 8.92;. N,N-dimethyl 3-(o-trifluoromethylphenoxy)-3-phenylpropylamine p-toluene-sulfonate which melted at 134.degree.-6.degree. C. after recrystallization from ethyl acetate. Analysis calc.; C, 60.59; H, 5.70; N, 2.83; F, 11.50; S, 6.47; Found; C, 60.36, H, 5.52; N, 3.12; F, 11.80; S, 6.66. N,N-dimethyl 3-(o-tolyloxy)-3-phenylpropylamine oxalate which melted at 160.degree.-62.degree. C. after recrystallization from a methanol-isopropanol solvent mixture. Analysis calc.: C, 66.84; H, 7.01; N, 3.90; Found; C, 66.82; H, 7.07; N, 4.17. N,N-dimethyl 3-(.beta.-naphthyloxy)-3-phenylpropylamine oxalate: melting point=145.degree.-7.degree. C. Analysis calc.: C, 69.86; H, 6.37; N, 3.54; Found: C, 69.80; H, 6.50; N, 3.74. N-methyl 3-phenyl-3-(m-chlorophenoxy)propylamine oxalate: melting point=177.degree.-9.degree. C. Analysis calc.; C, 59.10; H, 5.51; N, 3.83; Cl, 9.69; Found; C, 58.89; H, 5.45; N, 4.07; Cl, 9.24. N,N-dimethyl 3-phenyl-3-(m-methoxyphenoxy)propylamine oxalate: melting point=125.degree.-8.degree. C. Analysis calc.: C, 63.99; H, 6.91, N, 3.73; Found: C, 63.93; H, 6.90; N, 3.59. N,N-dimethyl 3-phenyl-3-(o-allylphenoxy)propylamine oxalate: melting point=159.degree.-161.degree. C. Analysis calc.: C, 68.55; H, 7.06; N, 3.63; Found; C, 68.67; H, 7.15; N, 3.83. N,N-dimethyl 3-phenyl-3-(p-chlorophenoxy)propylamine oxalate: melting point=139.degree.-141.degree. C. Analysis calc.: C, 60.08; H, 5.84; N, 3.69; Cl, 9.33; Found; C, 60.34, H, 5.95; N, 3.88; Cl, 9.61. N,N-dimethyl 3-(o-methoxyphenoxy)-3-phenylpropylamine maleate: m.p.=98.degree.-103.degree. C. Analysis calc.: C, 65.82; H, 6.78; N, 3.49; Found; C, 65.83; H, 6.52; N, 3.63. N,N-dimethyl 3-(p-methoxyphenoxy)-3-phenylpropylamine maleate: m.p.=101.degree.-104.degree. C. Analysis calc.: C, 65.82; H, 6.78; N, 3.49; Found; C, 65.96; H, 6.50; N, 3.68. N-methyl 3-(p-fluorophenoxy)-3-phenylpropylamine maleate: m.p.=112.5.degree.-119.degree. C. Analysis calc.: C, 63.99; H, 5.91; N, 3.73; Found; C, 63.77; H, 6.19; N, 3.90. N-methyl 3-(p-methoxyphenoxy)-3-phenylpropylamine maleate: m.p.=128.5.degree.-135.degree. C. Analysis calc.: C, 65.10; H, 6.50; N, 3.62; Found; C, 64.94; H, 6.54; N, 3.67. N,N-dimethyl 3-(o-bromophenoxy)-3-phenylpropylamine oxalate: melting point=144.degree.-6.degree. C. Analysis calc; C, 53.79 H, 5.23; N, 3.30; Br, 18.86; Found, C, 53.84; H, 5.52; N, 3.38; Br, 18.86. N,N-dimethyl 3-(p-tolyloxy)-3-phenylpropylamine oxalate: melting point=145.degree.-147.degree. C. Analysis calc.; C, 66.84; H, 7.01; N, 3.90: Found; C, 66.61; H, 7.01; N, 4.06. N-methyl 3-phenyl-3-(o-allylphenoxy)propylamine oxalate: melting point=144.degree.-147.degree. C. (dec.). Analysis calc.: C, 67.91; H, 6.78; N, 3.77; Found; C, 67.90; H, 6.85; N, 3.96. N-methyl 3-phenyl-3-(p-tolyloxy)propylamine oxalate: melting point=170.degree.-173.degree. C. Analysis calc.; C, 66.07; H, 6.71, N, 4.06; Found; C, 65.93; H, 6.57; N, 3.87. N,N-dimethyl 3-phenyl-3-(m-tolyloxy)propylamine oxalate: melting point=134.degree.-6.degree. C. Analysis calc.; C, 66.83; H, 7.01; N, 3.90; Found; C, 66.48; H, 7.32; N, 4.32. N,N-dimethyl 3-phenyl-3-(m-trifluoromethylphenoxy)propylamine oxalate: melting point=163.degree.-5.degree. C. Analysis calc.; C, 58.11; H, 5.36; N, 3.39; F, 13.79; Found; C, 57.89; H, 5.26; N, 3.41, F, 13.69. N,N-dimethyl 3-phenyl-3-(o-t-butylphenoxy)propylamine oxalate: melting point=146.degree.-9.degree. C. Analysis calc.; C, 68.88; H, 7.78; N, 3.49; Found; C, 68.56; H, 8.04; N, 3.69 N-methyl 3-phenyl-3-p-fluorophenoxy)propylamine oxalate: melting point=159.degree.-161.degree. C. Analysis calc.; C, 61.88; H, 5.77; N, 4.01; F, 5.44; Found; C, 61.66; H, 5.90; N, 3.72, F, 5.70. N-methyl 3-phenyl-3-(o-methoxyphenoxy)propylamine hydrochloride: melting point=105.degree.-8.degree. C. (recrystallized from ethyl acetate); Analysis calc.; C, 66.33, H, 7.20, N, 4.55, Cl, 11.52; Found; C, 66.16; H, 7.36; N, 4.41; Cl, 11.48. N-methyl 3-phenyl-3-(o-fluorophenoxy)propylamine oxalate, melting point=148.degree.-50.degree. C. Analysis calc.: C, 61.88; H, 5.77; N, 4.01; F, 5.44; Found; C, 61.83; H, 5.97; N, 4.14; F, 5.65. N-methyl 3-phenyl-3-(m-methoxyphenoxy)propylamine oxalate; melting point=140.degree.-3.degree. C. Analysis calc.: C, 63.15; H, 6.42; N, 3.88; Found; C, 62.91; H, 6.40; N, 4.17. N-methyl 3-phenyl-3-(o-tolyloxy)propylamine oxalate: melting point=155.degree.-7.degree. C. Analysis calc.: C, 66.07; H, 6.71; N, 4.06; Found; C, 65.81; H, 6.94; N, 4.36. N,N-dimethyl 3-(o-ethylphenoxy)-3-phenylpropylamine oxalate: melting point=152.degree.-4.degree. C. Analysis calc.: C, 67.54; H, 7.29, N, 3.75; Found; C, 67.33; H, 7.05, N, 3.98. N,N-dimethyl 3-(o-isopropoxyphenoxy)-3-phenylpropylamine oxalate: melting point=139.degree.-142.degree. C. Analysis calc.; C, 68.20; H, 7.54; N, 3.61; Found, C, 68.50; H, 7.82, N, 3.85. N-methyl 3-phenyl-(p-chlorophenoxy)propylamine oxalate: melting point=163.degree.-5.degree. C. Analysis calc.; C, 59.10; H, 5.51; N, 3.83; Cl, 9.69; Found; C, 59.33; H, 5.58; N, 4.07; Cl, 9.45. N,N-dimethyl 3-(p-fluorophenoxy)-3-phenylpropylamine maleate: melting point=103.degree.-8.degree. C. Analysis calc.: C, 64.77; H, 6.21; N, 3.60; Found: C, 64.79; H, 6.50; N, 3.82. N,N-dimethyl 3-(m-chlorophenoxy)-3-phenylpropylamine oxalate: melting point=150.degree.-2.degree. C. (recrystallization from isopropanol) Analysis calc.: C, 60.08; H, 5.87; N, 3.69; Cl, 9.33; Found: C, 59.90; H, 6.08; N, 3.42; Cl, 9.60. N,N-dimethyl 3-(o-fluorophenoxy)-3-phenylpropylamine hydrochloride: melting point=166.degree.-8.degree. C. (from acetonecyclohexane) Analysis calc.: C, 65.91; H, 6.83; N, 4.52; Cl, 11.99; F, 6.13; Found: C, 65.78; H, 6.82; N, 4.78; Cl, 11.70; F, 5.99. N-methyl 3-phenoxy-3-phenyl-2-methylpropylamine oxalate: melting point=158.degree.-160.degree. C. (from isopropanol) Analysis calc.: C, 66.07; H, 6.71; N, 4.06; Found: C, 66.12; H, 6.72; N, 4.26 N-methyl 3-phenoxy-3-phenyl-1-methylpropylamine oxalate: melting point=80.degree.-100.degree. C. with decomposition (from ethyl acetate) Analysis calc.: C, 66.07; H, 6.71; N, 4.06; Found: C, 65.85; H, 6.45, N, 4.20. .alpha.-dl-N,N-dimethyl-3-phenoxy-3-phenyl-1-methylpropylamine oxalate: melting point=113.degree.-16.degree. C. Analysis calc.: C, 66.84; H, 7.01; N, 3.90; Found: C, 67.03; H, 7.20; N, 4.13. N,N-dimethyl 3-phenoxy-3-phenyl-2-methylpropylamine oxalate: melting point=130.degree.-4.degree. C. Analysis calc.: C, 66.89; H, 7.01; N, 3.90; Found: C, 66.59; H, 7.08; N, 3.96. N-methyl 3-(m-fluorophenoxy)-3-phenylpropylamine oxalate: melting point=177.degree.-9.degree. C. Analysis calc.: C, 61.87; H, 5.77; N, 4.01; F, 5.44; Found: C, 62.07, H, 6.02, N, 4.23, F, 5.23. N,N-dimethyl 3-(o-ethoxyphenoxy)-3-phenylpropylamine oxalate: melting point=101.degree.-4.degree. C. Analysis calc.: C, 64.77; H, 6.99; N, 3.60; Found: C, 65.05; H, 7.00; N, 3.88. N,N-dimethyl 3-(p-fluoro-o-tolyloxy)-3-phenylpropylamine oxalate: melting point=149.degree.-51.degree. C. Analysis calc.: C, 63.65; H, 6.41; N, 3.71; F, 5.03; Found: C, 63.82; H, 6.66; N, 3.95; F, 5.32. N,N-dimethyl 3-(.alpha.-naphthyloxy)-3-phenylpropylamine maleate: melting point=97.degree.-99.degree. C. Analysis calc.: C, 70.48; H, 6.65; N, 3.42; Found: C, 69.80; H, 6.50; N, 3.74. .beta.-dl-N,N-dimethyl-3-phenoxy-3-phenyl-1-methylpropylamine oxalate: melting point=131.degree.-33.degree. C. Analysis calc.: C, 66.89; H, 7.01; N, 3.90; Found: C, 66.64; H, 7.00; N, 3.77. |
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