LU83830A1 - NEW PHENYLALKYLAMINE, THEIR PRODUCTION AND THEIR USE AS MEDICINAL PRODUCTS - Google Patents

Description

• Λ.

DE. KAPL tEOnkd GI3H Cs.se. 5/809 D — 7550 Bibers c-h 1 Dr. Fl./Kp.

Aiislana text

Chew phanyialkylamines, their preparation and their 5-shipment as medicinal products • New pr snylalkyla have been added to the present invention; · 1 ^ re rer general formula «1: 'À" 2 ^ ^ 15 Vÿÿ = \ ^ A-CH -Hi)

I B

p. / V

.- "" Λ R

U 3 their optically active antipodan, their diasteracissrs Eacsmate and 'V their optical antipodes, as well as their acid 5ddit? Cr. Salts, ins ™' <0 special demi ~ h ~ oi? 'Ri = ek> -.-- ··· - 1 e? r 5 r- ti ms sal z s v ~ k with inorganic or organic 5 "u.:en, medicaments containing them and process for their preparation.

Ale did clubs: m an rer - en rrivoils rbartrkc'o r; also have an effect, in particular an effect on the hard and the circulatory system.

In the above general formula I, jj denotes a hydroxyl group, an amino group optionally substituted by an AJ-karoyl group with 1 to 3 carbon atoms or an alkoxycar · - * bonyl group with a total of 2 to 4 carbon atoms, an alkylsmino or Diaikylaminogrupye, each A.lkylteil 1 to 3 carbonatorna anthaltan and are each substituted by a phenyl group, -R ^ - and R ^, which may be the same or different, Ealogen atoms, Trifluonssthyl-, Cyan- or Hitrogruppen or a 10th the residues R2 or also a Kass atom, w R & a Wassarstoffatoia or an A. alkyl group with 1 to 3 carbon planes, Ps; a Kess & rstoffatcia, a straight-chain or branched alkyl group with 1 to 4 carbon atoms, its CycloaikyIgrugpa 15 with 3 to 6 carbon atoms, an alkenyl group with 2 to 5 carbon atoms or an aralkyi group with 7 to 10

Carbon atoms, A is the methylene, ethylene or hydroxymethylene group and 3 is a group of the formulas p • ’3. .... 3.

1 //: -d 'Λ 7 20 where

Rp is a hydrogen or halogen tone, a hydroxyl group, a ge.ebenerof ails titrated by a F he..vlrr0: 05 av ~ alkoroy group with 1 to 3 carbon atoms, he *, an alkyl suif suy 1 or alkylsulfinyl group each with 1 to 3 carbon 25 nt ·:, -. · an, • v ....... ...... -. - - 3 -

Ry is a hydrogen atout, a hydroxyl group or an alkoxy group with 1 to 3 carbon atoms or Rg and Ry together are the aesthetic dioxy group,

Rg is a hydrogen atom or an alkyl group having 1 to 3 carbon atoms, D is an oxygen or sulfur atom, a sulfinyl or sulfonyl group, n is the number 1 or 2 and Ξ — one optionally by one or two alkyl groups each having 10 wsils 1 to 3 carbon atoms substituted straight-chain - alkylane group with 3 to 5 carbon atoms or, if ^ A a methylene or ethyl group and / ocer? Ί one by an alkanoyl group with 1 to 3 carbon atoms or an alkoxycarbonyl group with a total of 2 to 4 Carbon-atom-substituted amino group, a Hy-4-hydroxy, alkylsmino or dialkylamino group, each of which may contain 1 to 3 carbon atoms and js'ails can also be substituted by a phenyl group, and / or 20 r2 is a trifluoromethyl, Cyan or nitro group and / or Rg is a fluorine atom and / or

Rg is an alkyl group with 1 to 3 carbon atoms and / or

Rg is an alkyl group with 1 to 4 carbon atoms, an O cycioalkyl group with 3 to 6 carbon atoms, an Al- 25 ksnyl group with 2 to 5 carbon atoms or one

Ar & iky igrupps with 7 to 10 Koh 1 en substance atc-nsn and / or Rg represent a fluorine or chlorine atom, an .Alkylsulfenyl- or Al-.w kylsulfinylgruppe each with 1 to 3 carbon atoms, a StbyUn.crupps or also, w-rm A represents the methylene group, a group of the formula

V

! - ^ "2" r -n uer a e-i-xy 1 he around s "lit 1 to 3 carbon atoms.

I! ................. ...... - 4 - ....... .........

For the bai of the definition of the radicals up to R ^ and E previously mentioned meanings, for example.

for R1 oils are Kydroxy-, Amino-, Kethylan.inc-, Ethylamino-, Pro-pylaiaino-, Isopropylamino-, Benzylamino-, 1 -Phenyläthyl-5 amino-, 2-Phenyläthylamino-, 3-Fhsnylpropylamino-, Dimethylamino -, Diethylamine-, Dipropylamino-, Diisopro-pylemino-, Dibenzylaminc-, Di- (2-Phanyläthyl) -amino-, | - · Di- (3-? Henylpropyl) amino, methyl ethylamino, methyl! propylamino-, Kethyl-isopropylamino-, Kthyl-isopropyl- r> 10 εη.ίηo-, Kethyl-benzylamino-, Ethyl-bsnzylairdno-, Propyl- $ benzylamino-, Pyrrolidine-, Piperidinc-, Esxamsthyien-! imino-, forrryleroino-, acetylamino-,? ropicnylairiino-,: Methcxycarbonyl & minc-, Stbcxycarbonyjamino-, Propcxy-, csrbcxiylamino- or Isopropcxycarbcnylamir-ogruppe, iÿ for R ^ R ,, who know the same or different, each: that of the fluorine, chlorine, bromine or iodine atom Trifluor-! ' 'methyl, cyan or ivitro group or for? .2 or R, smelled that of the hydrogen breath, for R, and R ", which can be the same or different, each 4 Ô 20 that of the hydrogen atom, the methyl, Ethyl, Prcpyl i:} or isopropyl group, i: for R ~ that of the hydrogen atom, the methyl, ethyl, Piopyl ™,

Isopropyl, butyl, isobutyl, tert. Butyl, cyclopropyl,: cyclobutyl, cyclpentyl, cyclohexyl, allyl, crotyl, 25 pentenyl, benzyl, 1-phenylethyl, 2-FhsayläthyI, 3- Ί - phenylpropyl or i-phanylbety 1 green rge,

II

i 'for Rg which is the hydrogen, fluorine, chlorine or bromine atom, the

Eydroxy-, Ksthcxy-, Äthexy-, Pr.:g;u:y-, Iscprrpcuy-, Mathylsnlf er.yl-, Äthy la ul Jo.:y 1-, Methyl sulf ir.yl-, Pro-- 30 pylsulfinyl -, Benzyloxy, 2-phenyläthcxy- or 3 -? Heryi ~ propoxygruppe, - 5 - t for that of the hydrogen atom, the hydroxyl, methcxy, Äth-oxy-, propoxy or isopropoxy group or for Rg and R? together that of the methylene dicxy group, for Rg that of the methyl “, ethyl, propyl or isopropyl group 5 and for Ξ that of the ethylene, n-propylene, n-butylene, n-pentylene, - 1-methyl-n- propylene, 1-ethyl-n-propylene, 1-propyl-n-propylsn-, 1,1-dimethyl-n-propylene-, 1,1-dimethyl-n-propylene-, 1,1-dipropyl -n-propylene-, 1 ~ l'r £ hyl-1-methyl-n-propy-'7 10 len-, 1-methyl-1-propyl-n-propylsn-, 1-ethyl-1-propyl-n - prc-pylsn, 1-methyl-n-hüty] en or 1-cathyl-n-pentylene group into consideration.

The compounds of the general formula I in which R.sup.1 have an amino group optionally substituted by a benzyl group or an alkoxy group having a total of 2 to 4 carbon atoms, an alkylamino or dialkyleriro group, each alkyl part Can contain 1 to 3 carbon atoms, R2 is a hydrogen, chlorine, bromine or Koos ton, a Wrixluor-20 msthyl, cyan or nitro groups, {. ^ J a Fluor ™, chlorine or Brera tones or a cyano group, are a hydrogen atom or a methyl group, a hydrogen atom, a ce-cr «ben en felis substituted by a phenyl group alkyl group with 1 to 3 carbon atoms, an A.llyl or Cclclopropylgruppe, Ä the methylene, ethylene or Hydrcxyr. ethylax group and 3 a group of the formulas

Ro '//

\ = zJ ^ R

7. * -. ". - c. *,“ * -6--

- <3C

R7 badsuten, wobsi

Rgz D and n are defined as mentioned at the beginning, ^ Rg is a hydrogen, fluorine or chlorine atom, a hydroxy, ^ ksthoxy, ethoxy, benzylxy, Kethylsulfsnyl- or Ke- 5 thy1sulfiny1grupps, R? a sers tof f etom or an I-Iethoxy c rupps or Sg and together a Hathylsiidioxy griipps and E the n-Fropylsn-, l-Xethyl-n-propylan-, 1, l-Direthyl-n-Prcpylen- or n-Butylsngruppa or, if 10 A. the methyl or ethyl group nr-d / c or Rj is an amino group which is optionally substituted by a ferryl group or by an alkoxycarbonyl group having a total of 2 to 4 carbon atoms, an alkyl-amino or dialkyl group , each alkyl ax 15 may contain 1 to 3 carbons, u-nd / ocer fy R2 a trifluoromethyl, cyano or nitro group and / or a fluorine atom and / or

Rg is an alkyl group which may be substituted by a dhauylgrugye and contains 1 to 3 f chiens toi fat enen, which represent 20 allyl or cyclopropyl groups, which means ethylane group, bnecuders inexpensive own sebafs.

i

However, particularly preferred compounds of the general formula I mentioned above are those in which P: is optionally substituted by a substituyl-amino acid group, an alkyuinc or bialkylamino group, each alkyl part being 1 contain up to 3 carbon atoms ........ ": -7 - a fluorine or chlorine atom or the cyancruppa, a hydrogen atom or the methyl group,

Rj is a hydrogen atom, an alkyl group with 1 to 3 carbon 5 atoms which is optionally substituted by a phenyl group, the allyl or cyclopropyl group, A is the methylene or eydrexyir.ethylene group and 3 is a group of the formula kr · “£, where 7 S the n-propylane, 1-methyl-n-propylene, 1, l-dluethyl-n-yro-10 pylsn, n-3-butien group or, if Rj, the xthoxycarbonylamino groups and / or the cyano group and / or a flunratone and / or '' R_ is a 5 '- * "*' * 5 alkyl group with 1 to 3 carbon atoms, which is substituted by a chlorine chlorine, and an allyl or cyclopropyl group, also the ethylene group, Rg. sin hydrogenate, a hydroxy or butt rr group w and (Έ, η represent a hydrogen breath or a kethoxy group.

According to the invention, the clean connections are obtained by the following process: a) reduction of a compound of the al empty · a formula suy-C ’; I, ui> R1 i

R

3rd

-K

in. dsr to R3, Rg and B as defined at the beginning and X is a group Romaln, (4 - CO - CH -, OH R.

I I4 __ - CH - CH-, G-acyl

i I

(J - CH - CO -,! I - CH »- CO -, ü 2 Γ I f;. - - CH - CH - nder! Z? ..

'II4 - CH - CH «- CH - shows, where? ..

'I is as defined in the beginning, «fl I ^ Acyl an organic Aeyi group like the acetyl, propionyl · •. or Eanscyigr rr-pe and i Z one reductive ahsrrlibsre ridges via sin bread: - or Jc-i "I 10 or a Kchlonsänreesterrest such as the HathcxycarbGiiy.it] or Xihcxyeerbonyloxygrupps mean.

I · f The reduction is depending on Hsdeuiarr Grs Jw.T.ias X in sin.

3 l of suitable solvents such as xethenol, idstharol / kssser, • ethanol, ethanol / water, isopropanol, trifluoroacetic acid! 15 ishrrol, räthylätbsr, w-strahydrofv.ran, tetrahydrofuran I. i'tttar, dioxane or Herttrwihyl-rhct thcrrät \ tirianiet .r-w; f | räligerwaisa with a hydride, with aluminum! sopropy2at ’- Ge5tires primary or secondary alcohol, with. - · ’: - * - · v, i - er ·> '? "’ R ^ er 5 S d 3 *: z-1; CI 7 '"*'. Γ

Substance at? ... temperature between -20 ° C and the boiling point of the reaction mixture, e.g. at temperatures between -2Q ° C and 100 ° Cf.

By preparing a compound of the general Fermai I, 5 in which A represents the hydroxymethylene group, the reduction is expediently carried out, for example, with a complex metal hydride such as sodium borohydride or lithium aluminum hydride in a suitable solvent such as methanol, methanol / water, diethyl ether or tetrahydrofuran at temperatures 10 between -20 ° and 50 ° C, the reduction with aluminum isopropyl ether in isopropanol at boiling temperature and while distilling off the acetone formed, the reduction with catalytically excited hydrogen with hydrogen in the presence of a catalyst such as platinum, palladium, Eaney nickel or Ransy- 15 cobalt at room temperature and at a hydrogen pressure of 1-5 bar, and the reduction with shaving hydrogen, for example with activated metallic aluminum and vkeaer or with zinc and hydrochloric acid, at a temperature up to the sieving temperature of the solvent used.

on If X in this connection means the -CO - group in a compound of the general Ferrai 1Σ, the reaction becomes swacbmäSiger- (j at temperatures between 0 and 50 ° C, preferably at

Room temperature, e.g. with sodium borohydride in methanol / water, ethanol / water or isopropanol or with Lithinwaluminixrnhy-25 drid in diethyl ether or tetrahydrofuran as solvent, O-acyl or X die - CH - CO — G.-r.rrga, so the Ur.-settlement preferably with; : .- rgchud. in an am 5ig: - ·· -. · * on bc eune agents such as ether, Tetz · ahydrofuran or. Dioxane, e.g. 3. with diborane or lithium aluminum hydrium in tetrahydrofuran at low to 50 slightly increased Iruru: u .. 'e.'f e.g. at tuperatures between 0 and 100 “U, unuuilgu tft is carried out at the Siedet super n uu: the reactive vegetable base.

! ’’ - 10 -

The hydrogenation of a compound of the general formula I, in which A represents the methylene or ethylene group, inevitably the reduction is carried out with a hydride such as sodium hydride, lithium ammonium hydride, Hatrirrveyanborhydrid or | 5 pyridine boron in a suitable solvent such as ethanol, | . Isopropanol, tetrahydrofuran, dioxane, trifluoroacetic acid! or Hsxamathyl-phosphoric acid triamide at temperatures | between 0 and 100 ° C.

1 If X in a compound of the general Fcr- [10, II II the —C ^ —CC — group, the reaction is preferably carried out at elevated temperatures, e.g. with lithium, aluminum hydride Î in tetrahydrofuran at the boiling point of the reactive

Own, or X the Hydroxyäthyleiigrurps, it is preferably carried out with pyridine-borane in trifluoroacetic acid 15 at temperatures between 25 and 100 ° C, with the reaction components being relatively low at 7 nm.

peratursn, e.g. at -10 ° G, given Verden, or X

! - Z R. ’Z R.

; I I ^ I! ^ a -CH-CH- or -CK-CHj-CH group, the reaction i is preferably with Fatriunhorhydrid, Natriumoyanborhydrid 20 or Lithinmalurdniumhydrdd in ei: ·. · am Suitable solvent 1; such as isopropanol, liex ^ ethyl-ghosg.-hoi acid triamide, tetrahydrc

| furan or dioxane at temperatures between 20 and 10 ° C

• performed.

__ b) U: as ~ tcvng a possibly in the reaction mixture gsbil- 25 detsn carbonyl compound of the general formula il '* K - L, (III)!; in K suscwrnen with a neighboring via s s ers to f fa ton in. Alkyl part the rest L is a acid to ffa icm, f 30 l which for 3 or with the exception of the hydrogen atom that for l! ' R- has the meanings mentioned at the outset or a group li 5 ^ "represents formula - 11 -R4 t -CE - ^ £, vcbei I 1 R3 to R4 are as defined at the outset and Ä 'represents the carbonyl, methylene or ethylene group / or their Aidshyd hyerate with a 5 amine of the general formula

/ M

H - N '/ (IV) \

Q

: in the M and Q, which are different, for B and P. ~ einrares' c Q the Grappe of the formula R4!

I L

· 10 P represents, with 3 detergents.

ΙνΓ 3 Xr-tr 3X2-u.riCJ WXITCl v ΟΓ 4 J 'CH' vt: 1S 3 XU 0X "X ft jbîlXv '.' T. ': - ^ -r - w ™ 15 Ξν. Ounol, diethyl ether, tetrahydrofuran or Dicxan in that he was a reducing agent at temperatures between -20 - 12 - • i and 50 ° C / but preferably at temperatures between Ο I and 25 ° C. The reducing agent is a complex metal hydride or catalytically excited I hydrogen into consideration.

I'- 5 Is the reaction with a secondary amine of the general | Formal IV carried out, but this is preferably in I. Tetrahydrofuran as a solvent and with sodium cyanoborhy "| - arid at pH ^ 7, e.g. at pH 6-6.5 and then with sodium: triumborohydride at room temperature.

! O

! 10 is aie cmserzung with a primary amine of the general i formula IV, so the ge formed in the reaction mixture 1 see Ba.se preferably with a complex metal hydride such as Hatriur-borohydride or lithium a 1 rirdni rrky fr id, in a suitable solvent such as methanol, methanol / i -55 water, diethyl ether or tetrahydrofuran at temperatures between -20 ° C and the boiling point of the solvent used, for example, "bai ïenpsrît;. · enically at O and 80WC, c- ivc i with catalytically excited hydrogen, for example with hydrogen I in the presence of a catalyst such as platinum, palladium, 20 Raney-Hickel or Raney-cobalt, at a temperature between 0. and 10DW C, but preferably at room temperature, and at j Q a hydrogen pressure of 1-5 bar.

The methylation can also be carried out with formaldehyde and formic acid as a reducing agent for increased Tsmpsratuian, e.g. at the i _ 25 boiling point of the reaction mixture, Ï '

If the reaction with a 7-: mm m.:m 1er = .11-e ... a Par - i-mel IV, in which R. an amino or alkylnmiee: memes with 1 1 1 to 3 carbon atoms dsrsbellt , and a carbonyl compound of general distance! IXT, in which b has the meaning for ~ .j BP, carried out eo - .n d’eae ie.abeserdeus when using an appropriate excess it is alkyliart worth. ' - “13 - c) splitting off one or more protective residues from a compound of the general formula R; 4 «R5 'R2 ^ Att - CH - N' CT * -" J 31, (V)

- vV

* 3 Ï in which H ^ and vie are defined at the outset, 5 R.j1 which has the meanings mentioned at the outset or which is a gsscbüt-; ts K / druxy or amino group, Ä "those mentioned for A at the outset Has meaning or represents iQ group, R "" has the meanings mentioned for R_crancrs or oo represents a protective radical for an amino group and 3 * Gis mr jö smgang's erwannuen uecouzungsn oesr.'ü'c your h "\ R3 vg.

// * '6.-CH- (cH2) n-c · ^ yy ’y or

"E ~ C ^ .V

7 15 represents "Obei ly - - η -

Rg, D, S and n are as defined at the outset and Rg1 and which may be the same or different, have the meanings for Rg and at the outset or are hydroxyl groups protected by Sehiitrrasta, at least one of the radicals 1, A ", R ^ 'and / or 3' must represent or contain one of the protective residues mentioned above.

As residues of rubble, for example, acyl pegs such as the ethoxycarbonyl, acetyl, propioryl or eunroyl group or i 10dis busyigruppa and you for A "eis A.cetyl-, Ksthcxycarl onyl- cd he Äibcxycarbonyl- gtupua into consideration.

The ib: y "Iburg oi.v-.s der obz.vg5ua: .rt * n Aryl and / or Alkcxy-Crrbonylraste preferably takes place hydrolytically in a 15 aqueous solution solution, eg in water, isopropanol / water, T. 'iitruhy dxc * f uran / Was ser or D ioxan / W * ss er, in the presence of a sensory acid salic acid or sulfuric acid or in the presence of an alhalic acid such as sodium hydroxide or potassium hydroxide at temperatures between 0 and 100 ° C , at the SC Sieüstu: perztur des Erektion-yenivchrs «

Dis Aiuvaltnng si: »s Benzvlre & tes successfully veczucswsise hy- 1 I ~“ "^ dvc-genc-lyti5ch, e.g. with hydrogen in the presence of a gate --de? Ail? Diu: s / ldr.ls, in l-ceunc.emittsl "ie dsthacol, AL thzrol, T & sigsäuräthylaster dar glacial acetic acid, if necessary with the addition of an acid such as hydrochloric acid at Tasspe v ratures between 0 and 50 ° C, but above all with Rsum-", loyal stubborn, and -in.an d: : u: o. £ t: if iruwk '-: n 1 to 7 bar, preferably .. Zug-.eisa but from 3 to 5 bar.

d) For the production of a compound of the ailgarainan formula I, in - ··. · · · .----. · O --w- - ·: * r ~ er sto ff 2ton represents t .......... .......... '' 2 ........ "i '"

Snfchalogenation of a compound of the general form

- 15 -R

, 4 ^ R5 A - CH - N »^ VI)

<V

_ R3 in which R-, R- until Rc, A and B are defined as crancrs and; 3 T j d "

Bal is a chlorine, bram or iodine breath.

The de-calogenation is preferably carried out in a solvent, preferably with TitLphanylphcsphin in Bsnsol or toluene, with hydrogen in methanol, ethanol, ethyl acetate or tetrahydrofuran and in the presence of a hydrogenation catalyst or with a complex A'etsilhycri such as lithium or allyl Natrirm-diSthGXY'-Alminiirnhycrid in Ί0 tetrahydrofuran, dioxane or toluene. Depending on the used

Method is the reaction at room temperature or elevated o

Temperature, for example, be temperature en between 50 and r \ 'iSö' - ’C, and at normal pressure or moderate overpressure through-f}; when using Eaney nickel or palladium / carbon Ί5, for example, the dehalogenation takes place at room temperature and normal pressure.

a) Alkylation of a compound of the allc-mainen formula '' 4 u «’ / “5 R2 - CH - N ^. (VII) h,!

‘R

3 - 16 -! I in csr | R ^ bis and A are defined as above,! R5 "has the meanings mentioned at the outset or i _ a What ssrsfcof fatom and I 5 has the meanings mentioned for 3 initially, where, I _ if Rg" is not a hydrogen atom, at least one | the radicals Rg or a hydroxyl group or?. ^ a cege- | ; If necessary, an amino group substituted by an alkyl group having 1 to 3 carbon atoms, etc., the alkyl group also being I; 10 can additionally be substituted by a phenyl radical, must: represent.

! ü \ f! The reaction is carried out in a solvent such as water / ethanol, ethanol / water, tetrahydrofuran, dioxane, acetone or di-; rathylsulfoxide with an alkylating agent such as bathyl iodide, I 15 dimethyl sulfate, Xthvlbromid, diethyl sulfate, benzylbronide, i * 2'-Phsnyläthylbromiä or methyl-p-toluenesulfonate, if necessary i • if in the presence of a base such as ITatrc n lau ge or Kalirscast'' swsckmäE usually with Taunera your between -10 and i 5ö ° C, but preferably at temperatures between 0 and - i 20 30 ° C. However, the reaction can also be carried out without a solvent.

The alkylation of the nitrogen atom can also be carried out by means of formaldehyde / formic acid at elevated temperatures, for example at the boiling point of the reaction mixture, or with a corresponding carbonyl compound and a complex metal hydride, preferably with Uatriiameyanborhydrid at pH ^ 7, for example, i: v at pH 6-6.5, in a solvent such as Ta ss er / Te ethanol, 'ethanol, II ethanol / Tater or Tatrahpörofuran at tempera · - *., Doors between 0 and 50 ° C, but awe isa preferred for rauotange

S

jj DO rature.

y! i ί j / - 17 -

Furthermore, the alkylation of a phenolic hydroxyl group with a corresponding diazcalkane in a solvent such as diethyl ether or tetrahydrofuran at temperatures between 0 and 50 ° C., but preferably at room temperature. cperatur, 5 can be performed.

f) For the preparation of a compound of the general formula I, in which the R 1 is formed by an alkanoyl group having 1 to 3 carbon atoms or an alkoxycarbonyl group having a total of 2 to 4

Carbon ayomon-substituted amino group and no 10 material is: \ h

Aayiierung a compound of the general formula

R

, 4 r5 A - CH - N ^ »VtHI)

R

3 in which? -2 to R-, A and B are as defined at the beginning, with a (_ / compound of the general formula 15 Y "c0", (IX)

t KJ

in the R ^ q is a hydrogen atom, a I'athyl- of the xthyl group or an Älkcwygruppe with 1 to 3 carbon atoms.en red Y a nucleophilically exchangeable group such as a halogen, 20 a nitrophenyl group, an imicazolyl group or a solid of the formula -0-CCR "- represents.

OK

/> / I _ __ _ _______ ____________ __________________________________ ____________________ I - 13 -

For example, the reaction is carried out with acatyl chloride, acetic anhydride, propionic anhydride or a corresponding chloroformate, e.g. Ethyl chlorensisonate, which can also serve as a solution, if necessary in a solvent such as' tasser / tetrahydrofuran, di-! ethyl ether, tetrahydrofuran or methylene chloride, given- | "if in the presence of a base such as triethylamine or pyridine, i;" whereby a tertiary organic basa can also serve as a solvent on the same side, at temperatures between 0 and i 10 100 ° C., but preferably at room temperature.

r __ The reaction can also be carried out without a solvent | b) the.

g) for the preparation of a compound of the general formula I, in which D represents a sulfinyl or sulfrylic group: j -J5 oxidation of a compound of the general formula! . .

-4P

! ·, 4 r'5 j: A ® - n f, lM6 I] j] ^ CH - (CVn - S0m ^ r: 1 I R8 '; O r3, ij.) J in the. "* to Rg, A and n are cefimi-like at the beginning and m represents the number C or 1.

The oxidation is preferably carried out in a solvent, e.g. 20 in 'tasser, kîasser / pyricin, ethanol, l'ethanol, acetone, glacial acetic acid, formic acid, "· · i \ r MMMslMure your Tr if lucres sig acid, depending on the used oxidizing agent two-times!' performed at temperatures between -80 and 100 ° C.

'- 13 »~ .......................

For the preparation of a sulfinyl compound of all -rr.ainan formula I, the oxidation is expediently carried out using one equivalent of the oxidizing agent used, e.g. with hydrogen peroxide in glacial acetic acid, trifirroracetic acid or 5 formic acid at 0 to 20 ° C or in acetone at 0 to 60 ° C, with a peracid such as performic acid in glacial acetic acid or trifluoroacetic acid at 0 to 50 ° C or with m-chloroperbanoic acid in methylene chloride or chloroform at -20 to S0 ° C, with potassium metaperiodate in aqueous methanol or ethanol at 15 10 to 25 ° C.

)

To produce a sulfonyl compound of general formula I, the oxidation zwacLräSigsrwaisa with a biw.

15 two or more equivalents of the oxidizing agent used, e.g. with hydrogen peroxide in glacial acetic acid, trip * ’fluoroacetic acid or in ameleic acid at 20 to 10G ° C or -in

Acetone at 0 to 6 ° C, with a per acid such as formic acid or m-chloroperbenzoic acid in glacial acetic acid, trifluoroacetic acid, 20 methylene chloride or chloroform at temperatures between 0 and 60 ° C or potassium permanganate in glacial acetic acid, water / sulfur s 1-acid or in acetone at 0 to 20 ° C.

i jf h) Preparation of a compound of the general formula I in which D represents an oxygen or heavy atom and R5 does not represent a hydrogen atom:

Implementation of a compound of the general formula - \ t 4 / * 5 R-p ^ δ η * _ πη - n 2 n * 'ch - (ch) - v »(xi) 11, 2 n b" T r8

Rx -loin represents R.j to R, -, Rg and n as defined in the introduction, V is a nucleophilically exchangeable group such as an Ealogenatcsn or a sulfonic acid ester residue, e.g. a chlorine, bromo-5 or iodine atom, a p-toluosulfonylcxy or mathansulfonyloxy group, and A "'denote the methylene or ethylene group, with a compound of the general formula of ~ krRe h - d * y , (yii)

R

s 7 in dar 10 P-g and P, ~ as defined in the introduction and, v D * is an oxygen or sulfur breath. means, or their! }

Alkali or Srcalcali salt.

The reaction is carried out in a solvent such as chloroform, tetrahydrofuran, dioxane or toluene, but preferably in a pleasant aprotic LS; surcsmi.it a 1 -ia "mmmn, Jimaihylfc.:..r?mid for dinethyl-1 sulfoxide, zsgebauenfal 1s in mums an ar alkali gas such as xatmium carbonate, potassium carbonate, sodium hydroxide, sodium triumhydride or potassium tsrt, butylate at temperatures - h0 between -10 ° C and Siadal · unpamu for the var-ended solvent, for example at Tanpemaiu :: an between -10 and 100 ° C, but preferably at temperatures between 0 and 50 ° C 'rann j-2doch auoh - 21 -

Its connection obtained according to the invention is generally distant! I, vfelche contains one, two or three optically active carbon atose, can then be separated into their optically active antipodes, their diastereomeric racemates and the optical anti-5 pods thereof according to conventional cathodes.

A racemate of a compound of the general formula I above is preferably cleaved via a fractional crystallization of a mixture of its diastereomeric salts with an optically active acid, e.g. der D (-} - no acid, L (-5-) -IC a - 10 acid, dibenroyl-D-tartaric acid, dibenzcyi-L-veinic acid, (+} - carp-} - "* 10-sulfonic acid, L ( -} - Malic acid, L {+) candelabra, d- §% -bron- camphor-fT-sulfonic acid or 1-quinic acid and subsequent release of the respective optically active base. However, the facsmet splitting can also be carried out by Säuler-ehrc-m.atc · Graphically on 15 active substrates, for example on acetyl callulcse.

1 The pure presentation of the diastereomeric racemates takes place, for example, by fractional crystallization and / or column chromatography on an inert support.

Furthermore, a new compound obtained in this way can be sdend m-20 desired failures in their physiologically compatible £? .Loe with an-Qf organic or organic acids. For example, hydrochloric acid, hydrobromic acid, sulfuric acid,? ht s phosphoric acid, fumaric acid, Berr.stsinsäurs, lactic acid, citric acid, v'ainsäura or maleic acid in consideration.

The rent as starting materials v.-Mm -; -! Verb: · The general formulas II to XII are partly new. These are obtained by methods which are known per se.

r «« 22 -

Thus, for example, a compound cer allçenusiiïsn Formal II, in which X represents a -CO-CHR ^ group, by gases ts-ung of a corresponding Oi-halogen chain with a corresponding amine and a compound of "3. Igen-sinen formula II, 5 in which X represents the -d ^^ O group, by reacting a corresponding phenylacetic acid derivative with a corresponding- '5 den Fmin.

The compound of general Fermai III used as the starting material, in which A * represents the carbonylgrirr-ps and R ^ is a hydrogen-10 tVcm, is obtained: .mn bîbeispielsvraiss by Selendiorid-uJ Oxic? .Tic-n of a corresponding Acetcphsnons bsw. its compound is sllgamainan formula III, in which A * is a ksthylsn or «thylsn group, by converting a corresponding Hvüso ^ ueibinuung into sine ontspr '·: vende F ~ .I-ganrarl :: - düng bow.

15 by Aeylisrung an eutspachend en Kydrcxyverbincung with a corresponding Chloramai s as. 3? ura ester.

i.

One as Auogungostoif v.r; s ·;.: · date V: “u iuduo g only all guusinsn Formal V is obtained in spiel * · eise by v-oatoung of a corresponding C * X -phenylalkyl halide with a corresponding SCViuin.

A compound of general formulas VI, VII and VIII used as a starting material is obtained, for example, from Edithicn. si. ras u'riuuuu "': -u can C.-rhon-Sura-mids or' uaino-acstcgbaucuis.

25 A starting material uerucndata compound of the general

Formula X rarely gets uw'u g: ’~ -u. ; s du ob Λ * bpi · ’suurg an ont '* sorschsnâen lier eapto-Varbir.du;: g -.::-5 g a. V:, partly subsequent oxidation.

. ^ u.-; u-u: ucc ^ x v uu- uu rue. ·. ; g c er a.llc emeruen b-Fer. · si si now receives, for example, by alkylation of a corresponding phenyl alkylamine.

- 23 -

As already mentioned at the beginning, the new compounds have valuable pharmacological properties with low acute toxicity and with few side effects, namely an effect on the heart and circulation, in particular an effect on blood pressure, an antiarrhythmic and / or cardiotonic effect .

For example, the compounds A = 1- (4 -. 'Jaino-3,5-dichlorophenyl) -2- / N- / 3- {4-r.etho>: y - phenyl) -% propyl / -air; ino / "ltbanol, 10 B = 1-i4" Ämino-3-cyan-5 "fluorophenyl) -2- / N- / 3- (4-zr.ethoxy-phenyl) -pr opy 1 / -ir «e thy 1 amir of - a th an ο 1, C = 1- (4-amino-3,5-dichloro-phanvl) -2 - / _ N- (3-phenyl-propyl) -2-propylaîtiino / -âthanol hydrochloride, D = 1- Î4-Àûiinc-3,5-dichlorophenyl) -2- / N- / 3- {4-hydroxyphenyl) - 15 1 "iaethyl-propyl /" K: rthylaui no / " ethanol, X? - * · * «. ET —.-? -! * »· _ -R ~ v TU T" ï v _ V V 'r ^ T ** £ j r “i \ / i ^ J; DJ.-CΠχΟι." JJ ^ i.y-i. / —O. t-i-V-. ·. / S ~ lüethoxy-phsnyl) -propyl / -ariin-hydr ochloride,

KJ

F = N- / 2- (4- & aino-3,5-dichloropher.yl) ethyl 7-N- / 3- {4-chloro-phe-nyi) -prcpyl / -isoprc pylamine, 20 G = N - / 3-i4-chlorophanyl) propyl / “N- / 2- (3,5-ichloro-4-isopropylamino-pfc-ny1) ethyl / ~ ieoprcgy1 an in;: d H = N- ^ 2- (4 -Amino- 3-brcn- 5-cyan-pher.y!) -3ΰ! Ν / 1 / -Χ- / 4- (4-nethoxy-phenyl) -butyl / -methy larain fi - 24 - j J 1. Measurement of the contractility parameter dp / dt ___ or the resin f iC „cjyc fregu-snz on i ^ arkotisler-ben Kat.ssn ____ __ j. * Male and female cats weighing approx.

2-4 kg were anesthetized with pentobarbital matrium (40 wg / kg intra - 5 peritoneally) and Psntcbarbital-Katrium (3 mg / kg / h) was continuously infused to maintain anesthesia.

| ---- The animals breathed spontaneously.

The body temperature was kept at 3S ° C with a heating pad and an I 10 rlsrocsisfen.

i _ The pressure in the left ventricle was measured with a pressure that was advanced into the left ventricle through the right aorta! aufnehnver (Miliar? C 350) recorded and from the pressure signal dis tuw-ckanstiecsgesckv'iiidigkeit dp / dt with a Dirferensisv; r j. ί3 determined continuously.

j c 'The heart rate was continuously measured with a Grass Tachograph_ (Model 7P4). The trigger signal would be snt-1 -'- "either use an EKG or the left" antricular pressure curve ".

The parameters were registered on a Grass-20 polygraph.

; All substances were injected as a solution (water or polyethylene! {J glycol 200) into a V. saphena. The dose was; 0.3 rg / kg in each case.

; The rawiwala effect and the since after the application up to which the effect has decreased to half the maximum effect was given.

i “The following Τ-ù-silrn. contains: -n dis cafound value: i 'I'! | i l · jl / i!

v V

^ 1

Table I;

Substance% increase of "albuartusit dp / dt in minutes

[inax

A +93 38 5 B + 124> 140 C +83 112 D + 105> 100

Table II:

Substance% Reduction of I-Talbwertzeit 10 ’heart rate in minutes * ·· 1 1 _ | .. .......... _ ^ T, -, _ ^ ^ _____ ^ ___f S - 27 29 -? - 17 150 G - 13> 90 H - 14> 52 «1 15 2. Acute toxicity: Male and female mice“ dt a weight of approx. 20 g were given a dose of the respective early seasonings in sine V. saphena (0.1 bsw 0.2 ml / lO g body weight) or in the stomach. Do a 3 ο1. hey yours vrn 14 days r de die 20 LD-q using the Lichtfleid erd method Milcc.con order: - 26 -

Substance LD_0 IV p, o.

A 19> 100 C 32 250 5 Due to their pharmacological properties, the compounds prepared according to the invention are suitable for the treatment of cardiovascular and circulatory diseases. Thus, the compounds which have a positive inotropic action are particularly suitable for the treatment of heart failure, and the compounds which have decreased the heart rate are particularly suitable for the treatment of herbal vascular fluids and coronary herbal diseases.

For this purpose, the new compounds, optionally in combination with other Hirksucsi -zen, can be introduced into the usual ga-; Lenischsn Preparation en vie dragées, tablets, powder, cru re - 15 sitoria, suspensions, ampoules or drops. The adult dose is 1 to 4 times a day, 5 to 75 mg, but preferably 10 to 50 ~ g.

th The following examples are intended to explain the invention in more detail: / -27 -

Example 1 1- (4- £ aino-3,5-dichlorophenyl) -2 ~ £ Ν '* £ 3 · - (4 - *: T.aihoxy-phanyl) -pr © - py 1. / -mg thyl aming7-gthanol _ _ __ _ • To a solution of 3.45 g (9 nmol) 4 * -amino-3 ', 5' -dichloro-2-5 / N- / 3- (4-methcxy-pheny1) -propyl / -raethyl3 · * ln * V ”scetophenone in. = 40 ml of methanol and 15 ml of water, 0.5 g (13.5 ηΐίαΐ) potassium borohydride are added in portions. The pH is kept between 3 and 6 with 2N hydrochloric acid. After addition, stirring is continued for 30 minutes and the solution is concentrated on a rotary evaporator. The residue obtained is distributed between 100 ml of ether and 100 ml of 2N ionic acid solution. The ethereal r-b-sse is washed with water, dried with sodium sulfate and concentrated. The remaining oil is chromatographed with ethylene chloride: Ksihnnol = 19: 1 as eluent over silica gel (Macherey 15 and cone 70-230 mesh ÄSTM). Slide fractions,. which contain the desired compound was applied. combined, evaporated and the oil obtained in vacuo at 40 ° C freed from I-solvent residues.

ZE spectrum (methylene chloride): OH 2610 cm 1 20 'Π? 2 2400 -f 3430 cm "1 CH2 2850 + 2940 cm" 1 Q 0CH3 2S30 cm "1 ÎWdLkyl 2300 cm" 1 C = C 1610 cm ”1 25 UV -Spectrum (ethanol): "K max. 243 na (0.23): 2SO nm (0.08) 300 µm (0, C3): Exispie1_2 1- {4-'jrdno-3, 5-dichloro-pb · -.: yl) -2- £ lv- (3 “pbenyl-prcuyl}“ metbyl ™ 5Ç ;; - 3 ^ ± ar.ol-h '> d; .och.1:.: - .: 1 i __ ______ 10 g (0.035 Kol) 4'-amino-2-broa-31,51-dichloroacetophenone, 6.7 g (0.026 Kol) (2-? Baryl-psopyl) -r.ethylanin-hydi '.. zhlarid - (Cd -; · ώηά 10.5 ml (0.075 mol) of triethylamine cardan su 250 ml methylene chloride. This mixture is heated to reflux for 6 hours and then with power at RaumfceiKoa- i.- .

\. left standing, watch with water, over sodium sulfet j! 5 dried and concentrated on a rotary evaporator under vacuum.

The residual residue, consisting of crude 4 1 -amino-3 ', 5' -dichloro-I; 2- / N ° (3-phsnyl-propyl) -methylamine o7 "5eatcck3ncn is dissolved in 100 ml of il = SOliftm ethanol. While stirring and cooling with water, 5 g of catrium borohydride are added in portions. The mixture is left to stand for 10 hours at room temperature and rerjiürt excess: / -, Nstriiurhorhyörid with acetone. After dilution. vit water is extracted with | "Kethylenchlorid. The ethylene chloride rhase is removed separated, washed with water, dried over sodium sulfate and concentrated on a rotary vaporizer under vacuum. The gelfc- * 15hehe oily residue is with ZvathylsnchloridîEssigestsr = .j _; 4: 1 Ehrematogrschsch as eluent over silica gel. The ,, J | . Fractions containing the desired compound are evaporated. The remaining oily residue is in Iscorc- ·: j '. panol solved, with ethereal sales vre frightened and so lance | 20rait ether added until crystallization occurs. A colorless crystalline product is obtained.

: i Lard point s from E5 ° C (under sintering).

] Ü Example 3 1 Γ “-! \ 1 “(4’ ”Aaiiio-3,5-dichl or-phsnyl) -2 ~ / N- £ 3- (4-hydrc: cy ~ pheny 1) -1 -! 25 msthyl-prcpyl / -msthylamin ^ 7-Sthanol __ __ _ _______ - 29 - N Asooniak extracted twice with yes 250 al ether until basic reaction, then the ether extracts washed twice with 75 ml Nasser and dried with magnesium sulfate. The filtrate is concentrated on a rotary evaporator and the resulting evaporation residue is purified over silica gel 50 (Macherey and Nagel, 70-230 mesh, ASTM). A mixture of methylene chloride: methanol = 30: 1 is used as the eluent. The residue obtained after fractionation and concentration on a rotary evaporator crystallizes after inoculation. The crude crystalline 10 sat is recrystallized from methyl chloride and is present as a 1: 1 mixture of the diastereomeric racemates.

f

Melting point: 112-115 ° C.

Example 4 1- (4-Aminc-3,5-dichloro-phsnyl) -2- / N- £ 3- (4-methc-xy-pheny 1) -1 - • 15 mgthy1-proovlJ-methylamino / ethanol and the like ^ ...............

0.02 mol 1- {4 “Ar.ino-3,5-dichloro-phsnyl) (4 - hy drcxy-phsnyl)“ 1-methyl-propyl7 ”jEü2thylamino /“ ä'tharjol are in 22 ml 1 K I-'atronlauce and 10 ml Kasssr dissolved. 0.022 mol of 20% dissyl sulfate is added dropwise to this solution with stirring and ice-water cooling, and the reaction solution is stirred for 20 hours at room temperature after the addition of 50 ml of tetrahydrofuran. ; 100 ml of ether are then added, the organic phase is separated off, washed with 50 ml of 0.5N sodium hydroxide solution, 3 times with 75 ml of water and dried over magossive sulphate. The organic phase is concentrated on the rotary vial and the evaporation residue obtained is obtained via die-5Igel 60 etirey u. ’Bw1, - .70 - 230 mesh, ASTM) with methylene chloric: methanol = 30: 1 as - eluent cleaned. The oily Sinoamp residue obtained is freed from Le · s vng, ~ m 1 tteIreste in vacuo over sulfuric acid. The oil obtained is in the form of a 1 s 1-2 mixture of cd r.sts :: ao.-r-ren racemate.

- 30 -! vR spectrum (kefchylene chloride): CH 3200 - 3500 cm 1 brait j (below îïH2)! 0H2 34 30 -Γ 3 390 cm “1 5 CH- 2520, 2250 cm“ 1 4 .1

c 0CH- & ο: -0 CM

i 5 3 -ï). * »** AAjcy 1 rSeO cm j '’ OC 1550, 1510, 1435 cm “1 C = C V CH2 - Dsôermaiicn 1520 cm * 1 | W spectrum (ethanol): "X nax. 244 rca (0.27) Ί0 2S0 rca (0, C8)« _ 300 rm (0.03) · - (J '! Beisoisl 5 j ^ · 1- (4 -Âthcxycarbon5-f 1 before pr: capi} -2- £ ϊ- / 2- (4 - :: - = 4. H - o: rf-thenyl) -pr cpyL / -amlr, o / -gihs. Roi. ........ _ _ .....

I:. · 1 - 15 In a solution of 1.16 -g '(0.01 bel}' f-ilac.-î: * in 12 ml Di ™: l - c-xan and 0.7 ml Wessar cardan. Bai 60 ° C under? .Ühi ~ = n 0.5 g cs 11th and then 2.5 g (0.01 Hol) 4'-xthoxycarbony] = ".inοι1 31-cyan-5'-fluoro-acetophenone in portions The mixture is then heated for 4 hours to a saturated liquid, ti: 20 and then filtered from the undissolved solution, into the 3 · - · - {.] solution of 41-Ätfccxy-carbonylajnino-3 '-cyan-51 -fluorophenylgiycxal !!! after cooling and lowering with Sis 2.01 g (0.01 Kol); * 3 “(4“ Ketfcc - ?: y ™ phsnyl) -yrr ^ y2 v.vri ^ hgdr-ccb 'er: d and 1.01 g (0.01 mol)' triethylamine, dissolved in 12 ml of ethanol, approx. drips. The 1; - ^ \ _ 25 the crude 4 * -ethoxycarbonyl5minG-3 '-cyan-5'-flucr-phsnyl-gly- Γ oxylddsn-3- (4-r; 3thc :: y - pbccyl) ™ p, cpy "n contain,' a solution miré enter Söhren and Sv hl m with Sis p vr · ..: '?.;.:? I: .. mixed with 1.5 g sodium * i borhyerid and left overnight at? .Amiitar.peratur staher.ga- j' it is then destroyed with excess acetone sodium hydroxide, concentrated under Va. «:. *: rca to a small volume, mixed with Nasser and extracted with; : a vb pr =: ·; ch .1 ori d. Via Kethylanchiori d-Lös * ang is dried with Nasser gevas above, with Nshrium-j sulrat and carpeted to dryness in vacuo. The -31- remaining oily residue is chromatographed with ethylene chloride: methanol -20: 1 as eluent over 200 g of silica gel. The fractions containing the desired compound are evaporated. A colorless crystal-3 lines product is obtained.

Melting point: 111-112 ° C.

· Example 6 1 “(4-2tthcnycarbor: ylasino-3-cyan-5-fliior“ phauyl} -Ξ ~ £ Ν “£ 3- (4“ ic3th ~ osy-phenvl) -r-crvlA • r.atliylsm ^ inpy -âthaiîpl ^ _ 10 In a reading of 6, S g (0.06 Kol) selenium dioxide in 60 ml dioxane and 2 ml water at -50 ° C with stirring 15 g (0.0β mol) 4 '-

JithcxycarbonylnvinG'-S'-eyan-S '"fluoro-aoetephenen port:: räv: e5.' A. Then heated to BückfluStem-. · 'For 4 hours, then diluted with 100 ml of tetrahydrofuran and,' .t 15 is filtered off from the undissolved solution such as solution shown in FIG. 4 '-SthoxycarbonylasiDO-3' -cyan-5 * -fluorophenvlglye: ·; after cooling at room temperature, 10.7 g {0.06 mol) N- / 3- (4-Kethcxy-phsnyl) -propyl / -methyiam.tn, dissolved in 100 ml of tetrahydrofuran, is given. Su this solution is rare. Portions * 8 g of 20 (0.13 mol) Katriuscyanborhydrid, where c: ' a solution is added dropwise (3 wise addition of 2N hydrochloric acid at pH 6). The mixture is left to stand at power at construction temperature, mixed with 5 g of sodium borohydride and left to stand for 5 hours at Kaumj-rurparstur.

. Excess .'atrireborohydride is then destroyed with 25 acetone, diluted with water and extracted with methylene chloride. The Methylench / orid - lüung wi; · d gc · --see with water, over I’a ’. tri’sulfate dried and i.u v? 1 ----- ¾: .. 7 7. :::.: 1 ::.: · = u ~: de.apft.

- · The remaining oily residue is chromatographed wildly with Bssirasier as a 2luent over 700 g of KieseIgel. The Frsk-30 tiensn, which unites the gcdhr-chie connection anths'tsn, verdsn, singedapft and cas.:* oil in a '' vacuum at 40 “C freed from irritants.

! ! - 5c. - IR spectrum (methylene chloride): CH 3600 c: a 1! : m 34CO cm “1 I CH 2930 cm ~ 1 ^ -1 OCH., 2330 cm 5 N-alkyl 2800 cm '^ r CN 2220 cm" 1 HHCOOC2H5 1735 cm "1 UV spectrum (ethanol): A max. 223 nm (shoulder; 0.19)! 240 nm (shoulder; 0.12) | . io 285 r-m (0.06) CV - =? p2ht2-cia (ethanol + KGH): \ max. 223 nm (shoulder? 0.33) j b.7 2b3 - 265 nm (shoulder; 0.1} i 31S nm (0.06);! Hei? 11 ^ .7 H -! - 15E “ß- (4“ OJûino "3" brGïïi - phanyl) -athyl / "N" / 2 ** (4-r «ethcxy-phenyl) -: i.» Grc-cyl ^^ - si'hAtlrni'i ^ g.ihydrochlQrid · ___ ___ '_ hi | 2.9 g (0.077 mol) of lithium aluminum hydride are suspended in a stick Ί substance tmcsphMre in 100 ml of absolute tetrahydrofuran.

; A solution of 14.4 g (0.031 Hol) -Î- Α.τ.1ηο-3,5-di-! 20 brc-ss-E - / ^ - {4-n sthcxy-phenyl} -preçyl? -K-msthy 1-pbsnylsssigsä'urs- CJ enrtid in 100 ml of absolute tetrahydrofuran with stirring at Raur- ,! te "pers.tur rücke drips. Then the mixture is heated to reflux for one hour. Hit Essigaster and Chor he will be the excess * I LitMumalirainiuriiydrid rer and fo dropped along 10 n sodium hydroxide solution j.25 until the inorganic material pellets out cases.

! The protruding Tatrehydrofuran>? ? e is decanted ah, via S * 'JTatriums-ulfst ceirc-uk.o-t r.:d r; 3: t ·; v. 1 ~. ξ ~ = r: c "p · * -r i-engineering-go.

j) “· Hit ethylene chloride: methanol - 13: 1 as Ξ! u t io nsmi tt el becomes | over silica gel (Macherey and Nagel, 70 - 230 me .sh ASTM) chrcnst: -: 30 graphed. The fractions rlfc in -50/0 (0 = 0¾tan. Product has been combined and concentrated. Pos erb airs ne (51 is dissolved in vigorously nb should lut ethanol and the crystalline egg hydrochloride with etheric hydrochloric acid with S-- I using ether produced.

1 very -äln.p · .; -: Vts 162-171 ° C (h: r,).

_ X * 3 _ '3 si spla 1 3 ÏÎ- / 2 "{4-Αγ: Ιηο-3, S-dibromo-phsnyl) -äthyl /” N- / 4 “(4- :: -th; vy- gheryi) -baty37 "5isthyl5i5in _ 2.9 g (0.077 mol) of lithium aluminum hydride garden suspended in a nitrogen-5 atmosphere in 100 ml of absolute tetrahydrofuran. For this purpose, a solution of 15.0 g (0.031 mol) of 4-amiao-3.5 -di-bron-N- £ 4- (4-methoxy-phenyl) -butyl / “K-m3thy1-ph» ny 1 · ?.? s ig slur s-cmid in 100 ml absolute tetrahydrofuran with stirring at room temperature Rira RSek-- 10 fluS is heated an hour to the ass. With arsicaster and water, the excess lithium aluminum hydride is decomposed and 10N sodium hydroxide solution is soaked until the inorganic material precipitates as granules and on? .ccat: 'evaporator evaporated. · 15 With ethylene chloride: methanol = 15: 1 as eluentic acid, is passed over silica gel (Mschrrsy and Rigol, 70-230 rush AST: c) ch.vomatogra-nhisrt. The fractions with cn desired product are combined and concentrated. The oil obtained is freed from solvent residues in vacuo at 40 ° C.

20 IR spectrum (methylene chloride): NH, 3330 + 3470 cm 1 z -Ί; K-alkyl 2730 cm f}; 0CH3 2830 cm; slinhat. CH, 2350 + 2930 cm “1 1 _i C ™ C IblO cm 25 UV spectrum (ethanol) Zkrnax. 246 rm (0.24) 231 rn (0, C3) 305 r.m (0, C9) 1 - va -

T

Example 9 I II- £ 2- (4-amino-3-chloro-5-cyano-phenyl) -athyl / -N- £ 3 ~ (4-m-tkovy- i - ph ^ y3J ”proOviy-; ïsethyl5j ' nin _ _ ___ _____ _____ | 'i S- 6.6 g (0.014 mol) 1- (althoxycarbonylory) -1- (4-5 ^ * i: io-3-chloro-5- ·, 5 cyan “phenyl) -2 “/ N“ / 3'- (4-i23thoxy-phenyl) -propyj7 ~ K.athyls3iino7- il äthan are dissolved in 70 ml isopropanol and with 5.5 g (0.14 mol) j Katriuribcrhydrid at room temperature over power The 3/4 solution is evaporated to dryness and in 100 ml of water, 50 ml / 2 ml hydrochloric acid, the excess potassium [10/10 trinwiorhydride is destroyed ml 2 n Ämac- i! nisk again made baaich and twice with 150 al Sssigester

You or ganta ob a phase is keguesiunsulfat ga-tccuK.et and • singwengt. Γ-rs erb - Ile / · ’oil with methylene; ChloridiKsthanol = 19: 1 as unit: oruuittel over Kieseigel:. 15 (Kechr.cey and Kegel, 70 - 250: rsh 2 - .. S0M) Ehrcmatogr * ph iert. The . Λ Fractions containing the VeRrKndvng are pooled and evaporated, and the oil obtained is generally vacuum ;; freed from solvent residues at 40 ° C.

;; IS spectrum (KethyltDchlorid): NH2 3400 + 3500 cm ^ 20 K-alkyl 2S00 cm "’ alichat. CH, 2360 -r 2340 cm ^, \ z -1! ._ y aromat. C = C 1600 cm KH ^ -Dcformaticn 1625 cm 1 üv-spectrum (ethanol): \: u.x. '41 r: a (0.23) J. 25 273 nm (0.06) 1 .. 330 na (0.13)

Beieoiel__10: N- / 2 “(4-Aïïiino" 3-chloro-5-cyanophenyl) ethyl / “N- ^ 3- (4-methrxy- chenyl)“ "rc: rcl7 ^ t: ef.hy lamin __ _ _ _ ................. .......

30 1.3 g {0.0027 Kol) 1- (4-Amdnc-3-chloro-5-cyan-pher.yI) ·· 2- / N- / 3- | (4-uethexy-pbeny 1) -propyÎ? -R.ethy 1ämino / -Ithy1jodid in / - 35 - 30 rd. Heravethylphosphoric acid triaside dissolved. 0.25 g {0.004 mol) of sodium cyanoborohydride are added to this reading and the mixture is then heated at 70 ° C. for 3 hours. After cooling, it is diluted with 100 ml of water and extracted with ether. The ethereal solution is washed with water, dried over sodium sulfate and evaporated to dryness in vacuo. The "remaining oily residue is extracted on silica gel with methylene chloride methanol = 20: 1 as the eluent chromatograph. The oily india residue obtained is freed from solvent residues in vacuo. 10 mass spectrum: found M + 357/59 molecular weight: 357.8.

Example 11 1- {4 “ierknO“ 3 “t’luor --- ehenyl>“ 2- £ î- / 3- {4-nethosy-pfcenyl) -propyl / - vethylsnluc ^ -ethanol ____________ __________ _ _.

- 15 Biné solution of 3.9 g {0.0025 Kol) 1- {4-Ardno-3 ~ brcm-5-fluor-. . _. phsnyl) -2- / N- / 3- (4-r; Sthc: -: y-phenyl) -propv l / - r: sthylamino / -ethanol in 50 ml of methanol is mixed with 2 g of oily Palladius / charcoal and hydrogenated in an autoclave at room temperature and a pressure of 3.5 bar. After the theoretically calculated amount of hydrogen 20 has been absorbed, the mixture is filtered off and the filtrate is concentrated on a rotary evaporator. The 4 g of oil obtained are chloroform: Meth.ap.ol - 19: 1 as Eiuti.onsmittel on silica gel Cl'acl-erey u. Nagel, 70 - 230 ne sh ASTJi) chronatographed. The fzakticivsn, which contain the desired substance, 25 are varied and concentrated. The oil obtained is dissolved in isopropanol and the 1 edrochloride is precipitated with isoprepanolis hydrochloric acid and ethyl acetate. The crystals kz atg.%. 7? Vgt, "little washed in cold isopropanol and dried in vacuo.

Melting point: 110 ° C (dec.).

/; ’I ~ £ 2

Example 12 1 - (4- £ thexycarbonylsriinc "3 ~ àr o: u-eh · --lyl) - * 2- / Jl - /? ™ (î-eethoxy-phenyl) -butyl / -inethvl g: ntno / - -ä th?. :: ol

To a solution of 5.1 g {0.0125 mol) of 1- (4-amino-3-bromophenyl) -5 2- £ N- £ 4- (4-mathoxy-phsnyl) -butyl ^ -ifcs whyls: *: ino / ”ätIianol in 40 ml of absolute pyridine, 1.5 ml (0.015 mol) of ethyl chloroformate are added with ice cooling at 0 ° C. The received! The solution is stored in the refrigerator at + 4 ° C overnight. The pyridine is distilled off at a rotation at 50.degree. C.-10-a-n- \ 'scMii-Rond. The oil obtained is dissolved in 100 ml of methylene chloride and washed twice with 100 ml of water. The organic phtse is dried over sodium sulfate, filtered and sm Ho-| j 'tatic-rsverdan.pfer reptarnpft. The Q1 obtained is chronographed with Msthy-f Isnchloride: methanol = 3: 1 as elution medium over Kiessigel f »15 (Macherey and Nagel, 70 - 230 mash A5AM). The · !. Fractating bees that age the desired substance are combined and concentrated. The oil obtained is in vacuo at i; Removes solvent residues at 40 ° C.

j; -IR spectrum (methylene chloride): OH 3610 cm 1 [20 NH 3400 cm "1 |; OCH-, 2830 cm“ 1! Η * K-alkyl 2800 cm "1 ^ -1 aliwhat. CH0 2860 + 2940 cm Δ -1. “OO 173o cm 25 arc-mat. C ~ C 1610 cm 1 | _ UV spectrum (ethanol): λ max. 224 nm (0.42) 240 nm (0.29) - 280 rm (0.04); "R! ii, '- 37 -

Example 13 N- / 2- (4- £ mino-3,5-dichlorophenyl Î -ethyl7 ~ N- / 3- (4-hydroxyphenyl) -Tj ^ at ^ x ^ propyl / r ^ ethyla ^ in - _______ -0.012 mol of N- / 2- (4-Pmino-3,5-dichlorophenyl) ethyl / -N- / 3- (4-5 hydroxy-pbenyl) -1-methyl-propyl / amine dissolved in 13 ml of 1 N sodium hydroxide solution. O7OH mol of dimethyl sulfate is added dropwise to the solution while cooling with ice water. After a short time, the reaction product is greasy and is dissolved by adding 150 ml of tetrahydrofuran. The Reakticns-10 solution is left for 24 hours at room temperature stirred and then extracted twice with 150 ml of ether each time. The organic extracts are washed with a glass of green, dried over magnesium sulfate and concentrated in vacuo. with methylene chloride: methanol / concentrated ammonia 13: 1: 0.1 The oily evaporation residue is freed of adhering solvents in vacuo over potassium hydroxide.

IR spectrum (methylene chloride): OH 3530 cm 1 NH 3480 + 3380 cm "1 4+ 'Λ 20' CH, 2 = 30, 2850, 2850 cuf ^ -1! N-alkyl 2750 cm (j; C = C 1580 , 1510, 1480 cm "1; OC + NH2 De formst 5 on 1610 cm" 1 DV spectrum (ethanol): * h max. 240 µm (0.26; shoulder) 25 288 nm (0.03) 301 nm ( 0.08) UV spectrum (ethanol + KGH): ^ na?. 241 nm (0.56) I 212 itü (0.17) / <i 7 - <„ΤΟ _., - J '-> - \ i Example 14 ii 1 - (4 ~ Aiaino-3,5-dichlorophenyl) -2- ^ N- / 2- (4-zasthcxy-phenylsul-f inyl) - a thy 1 / - in ethy 1 si ~ 1 no / - ä tha π ο 1 _ _ ^, 7.0 g 1- (4- £ jaino-3,5-dichloro-phsnyl) -2- / N- £ 2- (4-rnethcxy-phenyl- 5 sulfsnyl ) -ethyl7-methylaraino / -starxol are dissolved in 100 ml of glacial acetic acid and 2.0 g of 30% I hydrogen peroxide are added dropwise with stirring at room temperature, stirring is continued at power I, at the same temperature, and then the solution is evaporated in vacuo. The residue is dissolved in water and mixed with Καί- · (\ μ '10 iium carbonate until a basic reaction. Man e extracted with dichloromethane, washed the organic phase with water, dried it with magnesium sulfate and evaporated in vacuo. The residue is cleaned anyway (column: 40 x 200 mm? Kieselgal 60, csr company E. Merck, grain size: 0.06-0.2 mm; n, 15 methylene chloride: methanol = 50: 1). Do evaporation of the ga-1. .. wanted fractions in a vacuum. hin L sab the c snaroits substance remains as oil.

IR spectrum (methylene chloride): NH2 3230 + 24c-0 cm jj CH2 2340 cm "" 1 20 0C52 2240 cm ”1 N-alkyl 2SCO cm" "1! J QC = C 1590, 1510 + 1480 cm 1 j * S ~ 0 1040 cm ”1 (shoulder) | \ "UV spectrum (ethanol): 7 * ~ -x244 rm (0.5 4) 25 300 na (0.07; shoulder) 4!" T "/: j i [, '" - 39 -

Example 15 1- (4 “Ä] TiirxO” 3,5 “Äichlor-phenyl) -2- ^ 1- / 2- (4-methoxy-phânylsuifo-nyl) - ä t hv IJ-me thy 1 am ino / - ethanol _____________________________________________ 7.0 g 1- (4-Pjaino-3 ', 5-dichloro-phsnyl) -2- / N- / 2- (4-ir.ethoxy-phenyl-' 0 5 suifenyl) -ethyl / -methylsmino / ethanol are, as described in Example 14, converted to the sulfinyl derivative. The residue obtained after evaporation of the dichloromethane extract (4.7 g) is dissolved in 100 ml of dioxane and 30 ml of water and treated with 4.0 g of 14a-magnesium sulfate. While stirring, 2.5 g of jf 10 powdered ral umperiucinganat are added in portions, Nacn becDucuer Sugobe is stirred for a further two hours and then the undissolved material is filtered off over Celite. The dioxane is removed in vacuo and 2V7iseöen dichloromethane and water are distributed. The Siröampfrüekstand the dried organic phase is cleaned swaimal chromatographisch 15 (1st column: 60 x 300 mm, Äl203 II neutral, Kethylen-chloriä: tetrahydrofuran = 5: 1; 2nd column: 3-5 x 300 sra, Kiesel- '- C3i 60, from E. Merck, Korr.cröSe: 0.015 - 0.025 mm, dichloromethane, 8.5 bar). After evaporating the desired fractions in vacuo, the g enciniifcs Sufcsto-üiz remains as an oil.

20 IR spectrum (ethylene chloride): NH2 3335 + 34 30 cm 1 * CH_ 2940 cm '^ 2 -1 v-v i OCH- 2S40 cm | 3 _ -j! N-alkyl 2800 cm C = C 1595, 1520 + 25 1435 cm ** S02 1150 + 1315 cm “1 GV spectrum (xthanol):% max. 241 nm (0.59) '- 300 ma {0.3 3) / Λ ggi-plel 16 ί - 4θ - \ 1- (4 «-Amino-3,5-dichloro-phsnyl) -2- ^ 5- ^ 3- {4 ~ ky £ roxy ~ phsnyl) -p :: c- I - "v lj-msthy 1 srrd nöj-a th anal _ _ _ 9.2 g 1- (4 * -amino“ 3.5 -dichlcr-phonyl) -2 ~ £ n- £ 3- (4-bsnzylo3cy-pha-5 nyl) -propy37 * 'IRöthylamirto7 -äthr.DOl «are dissolved in 150 ml methanol. The solution is dissolved with 1 g 5% icsr Falladium / carbon was added and the mixture was hydrogenated at room temperature under a pressure of 5 bar. After the calculated amount of hydrogen had been taken up, the catalyst was filtered off, the solution was evaporated on a rotary evaporator J io sur dry and the oily residue was mixed with methylene - | 1 chloride / methanol = 20: 1 as elution interface, chromatographed over silica gel, the fractions containing the desired compound

! T

anthslten, was combined, sinsdnnpft and the oil obtained was freed from solvent paws in vacuo at 40 ° C.

15 XE spectrum (Kethylanchlcrid): CH 35-80 cm 1 il 1 NH, 3355 + 3455 cm "1 'ί *" -1 ·: "K-Älkvl SoOO cm Γ

Example 17. • j ί o 1- <4 ~ Amino-3-bromo-phsnyl} -2- £ N- / 4- (4-mathcxy-phenyl) -butyl / - "20 rr-ethyl £ mlDo7-gthanol. ............................. _.................... ...........

! __ _ \ <3 g 1- (4-Acetcinino-3-brcïïi "phenyl)" 2- / lH "^ 4- (4-methcxy-pheryl) - f _ buty1 / -raethylsmino / -Mthanol are concentrated in 100 ml fcalbkcns i Acid heated to rear for one hour. After | v Cooling is carried out with 10N sodium carbonate, alkaline, arirahia :; £ îe. 25 with methylene chloride, wipes the liatiylanehlorid-Höarng with

Water, dries over sodium sulphate and evaporates in rotary evaporation. It evaporates to dryness. The zurö o’cbl -s ibard e oil is mixed with Kethy-

Isnchloride / methanol ~ 10: 1 as 51: 5: oiir.aittel clear kiesel gel chromatograph! The fractions containing the desired Var-30 bond are obtained by evaporation in vacuo at 40 ° C as an oil.

- 41 - "1 i IB spectrum (ethylene chloride): CH 3330 cm NH2 3330 -r 3470 cm 1 N-alkyl 2300 cm" 1 0CH3 2830 cm "1 5 aliphatic CH- 2350 + 2330 cm" 1 1 -1 arcm .C ~ C 1StQ cm ÜV spectrum (ethanol): λ max. 224 na (0.20) 243 nm (0.14) ί- v 0 am, Ο, ο 4) '300 nm (0.04)' j Example 18 1- (4-anino-3-cyan-5-fluoropheny1) -2- £ n- £ 3- (4-methoxyphenyl) - propvl7-msthylamlnQ7-äfchaaol __....... ...... ^ __

Made from 4 1 -Amino-31 -cyan-5 * -fluor-2- £ N- £ 3- (4-Reibc-xy-15 phsnyl) “propyl7-sathylamiiio /“ acstophaaon and Katriur-Vctchydrld - .. 'in 30% igsm methanol analogous to Example 1.

I spectrum (Ksfckyleiichiorid): OH 3550 cm 1 KH2 2400 + 3430 cm "'GH2 2850 + 2940 cm" 1 20 OCH. 2830 cm “1 s -1 N-alkyl 2800 cm O CsN 2210 cm” 1 NH - deformation 1635 cm 1 - -1, aroma. C-C 1 IS 10 cm 25 uV spectrum (ethanol): \ max »242 nm (0.3) 325 nm (0.14).

Example 13 1- (4-Amino-3-brcm-5-cyan-p! Vsnyl Î -2- ^ K- £ 2- (4-methc: *: y-ph eny 1) - _ ..... ........_ _ _________________ · 30 Made from 4 '-Amino-31 -brcrn-5' “cyan-2- / kï · - / 3- {4-methoxy-phsny 1) -propylj-methylami .no / “acetophenone and sodium borohydride in. SOîiçera Netiano 1 analog for stem 1.

/ - --2 - "23 Späktrca {I-Tskhylen Chlorid): OH 3590 cm 1 schuch KH2 3400 + 3450 ca ™ 1 CH2 2850 + 2930 cm 1 5 CrÜ 2200 ca" 1 OC 1S40 ca "1 UV spectrum (ethanol ):% rru.x. 243 nia (0.20) 280 µm (0.04) 334 nm (0.12).

10 Example 20 t (3 1 ~ »5-dibromo-phcnyl) -2- £ î- £ s- (4-methcxy-phenyl} -pro- pyU-ssthyl aalna7-gthaaol

Hsrg-divides from 4 1 -. \ Minc-31,5 '-dibcca "2- (i-Ui3thcxy“ pbsnyl} * picpyl / »ir.ethy.l £ 3ir: ^“ cccï' '. Cc' -. N : icn r:> 5 Nnfcrivrùcrhvirid in 30% - 15 igsm methanol analogous to example 1.

ÄE-Sp-ectmat (KethylenchXc-rid) ï CH, 3530 ca 1 HH2 3330 + 34 SO ca ”1 H-alkyl 2300 ca 1 0CH3 2830 ca“ 1 20 aliphst. CH2 3550 + 23 40 cra "1 C = C 1510 ca" 1 uy-Spsktrua (ethanol): ^ max. 2 * 14 nm (0.15) • '303 nm (0.06).

Example 21 25 1- (4-3.iair; G "-3,5-öichlcr-phenyl) -2-Ζ.Ν- ^ ΐ, 1-dimsthyl-3- {4-methoxy-pheny1) -propyl? ~ £ ndnö7 ~ S th anol _ _t .........

Hergestej.lt aas 1 - (4-.¾ ine-3,5 ~ dichlc-r - u 0er.yl) -2- / ÎÎ- / 1,1 -di-ir; ethyl-3- (4-hydroxy ~ phsnyl) -propyl7 ~ s.iT.iii <27 “ether nol, tetrahydrofuran, sodium hydroxide solution and bimethylsulfate he a log -nisnlel 13. oil.

50 IU spectrum (methylene chloride) in CH 3200 cm 1 NH. 339-0 t 3490 cm “1 CH. 2560 -fr2960 approx r.-l -..- 1 ...... 3 ...... - - 43 - f *.

UV spectrum (ethanol) s "X rvix. 243 rm (0.-23) 2SO rati (0.03) 2CO rcn (0, C3)

Example 22 5 1 "(4- £ mino" 3,5-dichloro-phsnyl) "2" £ N- £ I, 1 -dijr.ethyl-3 "{4-aethoxy-

Phenyl) "propyJL / -ni3fchyl5nilno7 ~ Sthariol '^ Made at» s 1 "(4-Ämino-3,5-dichior-phenyl) ~ 2- / N- £ f, 1-di-msthyl-3- (4- hydrcxy "phenyl) propyl / ~ aiüIri07" ethanol,

Tetrahydrofuran, Kstronl & cge and Diaefchylsulfat analog 3si-10 game 13. Oil.

Calculated: C 61.31 H 6.86 CI 17.24 N 6.81

Found: 61.13. 6.99, 17.25, 6.75

Example 23 1- (4 “Sinino“ S-chloro-S-trifluoromethyl-pheny1) -2- (4 “iuethos-: y“ {Jt 15 phany 1) —oropylT-ras thvlaminp / ~ ethanol • Herceetellt ans 4 1 - A ^ rdira-3 1 -chlor-S1 -trif lüor7nethyl “2- / N“ / 3-- (4-raathery-pheayl} -propyihy I e-tdno? - · e ee tcphancn and üîatriumbor-, r feyörid in 80 % in methanol as in Example 1.

IR spectrum (methy T.snehXorid): CH 3550 cm 1 * 20: ry 3210 + 3510 cm "1 K-Älfcyl 23:00 cmf1 OCH2 2830 cm 1" liphaf. CH2 2350 ❖ 2320 cm ”1 C ~ C 1o30 cm 1 25 ÖV-Scektrüm (ethanol) ϊ Xnax. 225 nm (0.36) 245 nm (0.31 210 nm (0.05) 3 years ... (0.7).

y - IsLj. - ψ

Example 24 • 1 “(3,5-dichloro-4-hyroxy-» phsnyl) -2- £ Ν- * £ 3- (4 ^ sthoxy ~ phanyl) -prc ~ ρ γ Γ / τα athy 1 ara i π oj - gth & η ο 1 _ __ _ __

Made from 3 *, 5'-dichloro-41-hydroxy-2 - ^ - / 3- (4-raethoxy-5 phenyl) "propy.] ^ - er; 3thylcj3ina / -eeeiu: sphenone and Nairiur-borohydride: in SOSigem Methanol analogous to example 1.

; "SchnislspunJct: 156-157 ° C.

\! | '3ebeispiel_25 j 1- (3,5-Dibrorû “i-” hydrosy-phenyl) “2- / N- / 3- (4-nethoxy-phenyl) - | io Sircuvi7-j ^ efchvlaaino / - ätbanol:

Made from 31.5, -Dibrc.rs-4 ’“ hydrc: xy-2- / N- / 3- (4-ir.etfcaxy-phenyl) -propyl7 ~ in3thyl £ ininc / -ao5toplieron and 'Katriuiüborhydrid i. in methanol similar to Example 1.

Scraps of the 15S-162 ° C hydrochloride.

15 Example 26:; 1- (4- & rdno-3-brcKS- 5- fl uer «ph eny 1} -2- £ ϊ- £ 3 ~ (i'-orathoxy-phsnyl) - ί O ~ propyiy-ms thyl c3i no./- a th elioI · | "i; - Made from 4 '~ ΐρα1ηο“ 3' -brcni ~ 5 * “f 2uor-2- £ K- / 3'- (4-iüethc: cy-? |; phenyl) -propyl7 -r <sthyl- = isinc / -a.cetophrnon and Katriisihcrhydrid | "20 in 80% methanol analogous to Example 1.

j 'Peeling point of the Hydre chlor id s iarergh): ah SO ° C.

| ~ Example 27 • 1 “(4“ ii ;; ino ”3“ ehlor “5“ fluor “-phei: yl} -2 - /: î- / 2- (4 ~ Dethc-: ey-phsny 1} - \ pl.O: -1 · /-./*'* · *. :: Sun "'·'. *. Γ;! '' ....... -" '1 __ ^ ^ ^ ^ ^ | | | 25 Manufactured from 4 1-Brairao ™ 3 • --chlor-5 * -f luor-2- £ N- / 3- (4 ~ iaethorcy— ί pi er.y!) -Propyl / · .. g -.- hy 1 r · · * · sets phenon and! 'atriv ~ horhydrid - »« - 45 - in 80% Mathanoi analogous to example 1.

Melting point of the hydrochloride: 103-108 ° C (dec.).

Example 28 1- (4- £ mino-3-chloro-5-cyano-phenyl) -2- £? - £ 3- (4-methoxy-phenyl) - 5 pgopyî7 ~ îRetliylaiûing7 ~ ethanol

Made from 4 * -Amino-3 * -chloro-5 '-cy an-2- / N- / 3- (4-methoxyphenyl) -propy ^ -msthylsminc ^ -acefcophsnon and Hat ri rnborhydr id' in blessed methanol analogous to example 1. it “-1 'IR spectrum (kaihylene chloride): OH 3590 cm 10 im2 3400 + 3500 cm" 1 N-alkyl 2300 cm 1 OCH, 2830 cm "1 aliphatic. CH2 2550 -f- 2S40 cm 1 • · .ChN 2210 cm ”3 15 * C: ~ C j 1525 cm 1 UV spectrum (ethanol}:" K rr: ax. 245 nm (0.26) 273 rm (0.06) 332 nm (0.15 ).

Hslsoiel 29 - kV: 20 1- (4-Amir <oS-chloro-S-nitro-pbsnyl) -2- / N- £ 3- (4-msthcxy-phenyl) - prop '? L7 "aethvl5mino /" äth £ aol

Made from 4 1 -Amino-31 -chlor-5 '- nitro- 2- / N- / 3- (4-msthoxy- ^ phenyl) -propyij-msthy1 amine o / ~ a ce tc-ph o:? c.-n and Ns t r iumborhydrid • in SGäigsm methanol analogous to Example 1.

_i - .. 25 IP spectrum (ethylene chloride): CH 3590 cm NH2 3390 + 3500 cm ”1 M-Alk · * -! 2800 cm 1 • _ * wl -j ~ û -. · W \ ^ a aliphatic. CH2 28 30 * 5- 2940 cm 30 c ~ C 1530 cm 1 NO 1330 - 1515 cm "1 ν '^ - 4 · ο - UV“ spectrum (.ethanol): ^ max. 227 nm (0.64) 280 nia (0.16) 400 r .: a (0.12)

Example 30 i I «i ΙΠΙΓ- ini.i——; 5 1- (4-Â! Rdno-3-chloro-ph: 3nyl) -2- £; - £ 3 “(4-i ^ etlbcxy-phenyl) -prcpyl / - - msthylairdno / - · äthanol __! -

Manufactured s.ns 4 '-Omina-3' -chlQr-2- ^ K- £ 3 "(4-maehcxy-phenyl) -,. Q prcpyl / "'ir-stl" ylaiaino / -acetophanon and sodium hormone in SOS-a igsïïi methanol analogous to Example 1.; —1? 10 IR spectrum (aesthetic chloride) î CH 3600 cm; NH2 33SO + 3470 cm ”1 \ N -Alkhat 2300 cm 1 '.v - 0CH3 2830 cm ”1 j -. · Aliphatic. CF- 2650' + 2940 ca“ 1; ". e.g. -1: 15 C = C _ 1620 cm; „ÜV spectrum (sthanol) Λ-sax. 225 rua (0.44) | 243 nm (0.36) 280 nm (0.03) * 295 ris (0.03).

; ΓΛ: i; · '20 Bsisciai 31 i -! 1- (i'-lmino-S-brcm-phenyl) "2- / N- / 3- (i-nethcny-phenyl) -propyl / - methylaïïiino / -gthanol; - Hergsstallfc from 4 * -ljainD-3 '- Krem “2 ·“ / ': 1 · - / 2 · - (4-- :: sthcrcy-phenyl) - · propy ^ 7 “metiiylamino /“ acetcphe: ivn rnâ F -tri vnborhy à r id in 50% - 25% methanol analogous to Example 1.

Melting point of the dihydrochloride: 137 ° C (dec.).

, "” ’~ - 47 _ *

Example _32 1 "(4-Airdno-3, 5-dicyan-phsnyl) -2- / N- / 3- (4-nethcxy-phenyl) -propyl / -methylamino / - ëhhanol _

Prepared from 4'-amino-31,5'-dicyan-2- / N- / 3 ~ {4-raethoxy-phenyl) -5 propyl7-methyl £ iaino7 "acetophenone and îîatriirnborhydrid in 8Q% - '¬ Kethanol analog .Example 1.

; -Schiae 1 zpunkt of the hydrochloride: 167-170 ° C.

i i

Seispie 1_ ^ 33 O f ~ "^’ ’1- {4-Amino-3-brGm-phenyl) -2- / N- / 4- (4-methoxy-phenyl) -hutylj-10 me • chylgjginQ / -ätfcaiiol

Prepared sus 4 1 -Amena-3 * -brem-2- / N - / _ 4- {4-neth.oxy-pheny I) -butyl / -iristhylaîsino7-acôtophxsnon and sodium borohydride in SOlicam Kstksaol analogous to Bsisoial î.

"1 IS spectrum (Kathyji chloride): CH 3 = 90 cm * r 15-NE, 3350 t 3470 cia * 2 -1 N-alkyl 2sQQ cm; 0CH3 2S30 cm’1 | -aiiphst. CH, 2350 -t 2930 cm “1 i C = C 1620 cm“ 1 {i i * 20, ’ü'v ^ Spsptrum (ethanol): Amax. 224 nia (0.44) 243 ns (0.28): 230 ma (0.08) 300 nm (0.06).

1 - 3rigolai 34 25 1 - (4-Ajnino-3-bros-pheny1) -2- / H- / 2- i 4-methoxy-phenyl) -styl / - inathylamir? O / -âth5iiOl ____________________________, _

Bergestelite from 4'-amino-S * -broie-2- / K “/ 2- (4-: îi-3thcxy-piisnyx) -athyl7-ir.2thylaiaino7-acetophenone and sodium borohydride in 80 ml of ethanol as in Example 1.

- -> äR-Spelrirum (Kethylenchiprid): CH 3530 cm 1 NH2 3330 + 3470 cm '' 1 N-alkyl 2800 cm ”1 0CH3 2S30 cm” 1 5 aliphatic. CH2 2840 + 2340 cm ”1 C = C 1620 cm 1 UV spectrum (ethanol): max. 225 rua (0.43) 243 nm (0.36) - 280 nm (0.08) 10 296 nm (0.08).

(3 Example 35 Ί- {4 “'.: ·' 1γ.Ο“ 3,5-5ichlor-phsnyl) -2- £ N- £ 4- (4-nsfchc;: y-phesyl) ~ hutvl7 “^ 3thvlgirtiaQ_ / -gthsnol ...........__.....

Manufactured eus 4 * -Aiaino-3 *, 5 '-dichlor-2- £ <- £ 4- (4-methosy-phs-. 15 nyl) “butyl / -methyl £ iaino7-acetophenone and Nafcriumborhydriâ in 8Q £ ± çem Methanol .analog example 1.

IR spectra (Kethylenchloric): GH 3550 cm 1 · KH, 3330 + 3430 cm ”1 1 _1 N-AXkyl Ai00 cm 20 '0C" 3 2530 cm ”1 | aliphatic. CH2 2850 + 2330 cm” 1 _ ^' C = C 1610 cm "1 ü7" spectrum (ethanol): 245 nm (0.25) 320 nm (0.43).

25 Example 36. 1- (4 "£ mino ~ 3-bi'om-5" cyan ~ phenyl) -2- £ 7 - * / _ 4- (4 "jr: ethc.ty" phenyl) - bOtyl / ^ methvlarâino / ^ gthanol

Herçestallt eus 4 1 “Amine-3 '-bi cm- 5' - cya n · 2- / 5-ß- £ 4-nathc my-ph2nyl)“ butyl / -m3thylsminô7 * -acetophanone and sodium borohydride in 30 80% igera methanol analogous to example 1.

'-49-> lB ~ Spsktruia (Kathyleîïchlorid): OH 3550 cm 1 NH2 3350 + 3490 cm 1 N-alkyl 2300 cm 1 OCH, 2320 cm “1 5 aliphatic. CH2 2350 + 2930 cm - CsN 2210 cm "1 C = C 1620 cm” 1 UV spectrum (ethanol): 7 ^ rcax. 245 na (Of27) 278 nia (0.08) 10 330 ma (0.15).

'"> · · ... / Example 37 1- {4“ & ainO "-3-bromo-5-C5an-ph2nyl) -2- / N- ^ 2- (4-sethcxy-phinyl) - Ι ^ Ϊ1Υ- ΐ7 ~ methyl? J% ino7 "ghtanol ___

Made from 41 -amino-3 '-brcm-5' -cyan-2- £ î - / [2- {4 ~ iasthcxy- 15 phenyl) -Sthy] / - methylamine / -acetcg> hsnon · and sodium borohydride in 80 % içem ethanol as in Example 1.

IR spectrum (methylsnchloride) s 0H 3590 cm 1 NH2 3330 + 3490 cm “1 H'-olkyl 2800 cm 1 20 OCH, 2830 cm" 1 -110 aliphatic. CH2 2850 + 2950 cm C = N 2210 cm "1 OC 1620 cm W spectrum (ethanol): \ max. 245 ma (0.25) 25 277 nm (0.09) 331 ma (0.10).

- Example 38 1 - (4-Jüaino-3, 5-dichloro-phsnyl) -2- / N- / 2- (4 ~ mathcxy ~ pbanyl) -athy1 / - ______. ____ 30 Made from 4 1-Amino-3 1,5'-dichlcr-2- £ N- / 2- (4-œathoxy-pfce-nyl) "• Sthyl / -r.3thyla.iaino / - 'acetcphar: cn ur.d Has ri urbcrhydrid in - BQ - SC-liçem l'athanol as in Example 1.

Sp-spectrum (methylene chloride): OH 3530 ea “1 KH2 3350 + 3450 csa“ 1 H-Al’iyl 2300 cm 1 5 OCH ^ 2830 est 1 aliphatic. CH2 2350 + 2930 cm "1 C-C 1610 cm" 1

Example 39 1 - (4- * laino-2-ehlor-5- sy an phsr.y 1} -2- £ N- / 4- (4-i5ethoxy-phenyl} - ££ * 0 butyl7 ~ æefchylgmdrvo / ~ ethanol ____________________________

Made of 4 * -Amine-3 '-chlor-5 * -cyan-2 - /! Î- / 4- {i-rssthcîqp- ph £ nyl) “biityiy“ iuethyl3i2ino7 ~ «cetopI'iai: cn rcd ITatr: * /.· _bc:; r.hydrid in SOtiges methanol analogously to example 1.

• _ IE spectrum (Kethÿlencfelorid): OH. 3:50 cm 1 · 15 * ϊ ·: κ7 · 3400 D 3500 cm “1 îl-A.ikyl Vc-00 cm 0C33 2330 cm“ 1 aliphatic. CH2 2850 + 2530 cm "1 C ~ H 2210 cm" 1 20 OC 1625 cm "1 UV spectrum (ethanol): \ max. 245 am (0.23) O 280 nm (0.05) 332 rm (0, 13).

N,

Example 40 - ^ ^ 5l- (4 «£ jr ^ o-2-ehlor-5 ~ cys.n ** pk-.nyl) * 2 ·· '/ O £ 2--' i - m _; -: y-ph.snyl} ~ - Sthyï? -îaethylamino / -Sthanol ........., _____.._

Made from 41-Ajaino-31-chloro-51-cyan-2- £ N- £ 2- (4-methoxy-phenyl) - “thyl7-3'2 thy 1 ami: · '. · O? · - a c etc rkanm er · a? 'S trinmh orhydride in SOI methanol as in Example 1.

S

* - 51 - IH-Spaktrca. (Methyl anchloride): OH 3530 cm “1 NHj 3390 + 3490 cm 1 N-alkyl 2S! D0 cm 1 OCH-, 2330 cm 1 - cr 3 -1 -. · · -5 CH J 2350 + 2340 cia C ~ N 2210 cm “1 C ~ C 1β 20 cm 1 ÜV-Spaktruni (ethanol): max. 245 nm (0/24) 280 nm (0/04) 10 332 nm (0.13).

4 \ Example 41 1 - (4-Aœino-3,5-dichlorophenyl) -2- / 11- / 2- (4-msthoxy-phanylsul- * fenyl) -sthyl / -msthyl ~; rdn; o / " gth ~ nol __ ...... _ _ __. Made from 4 * -amino-3 ', 5'-âichlor-2- £ N- £ 2 * - (4-nethc2ry-ph3- 15 nylsulfsny1) -athyl7 ~ mathylamine / - acatc-phanon and üftriumborohydrid in tetrahydrofuran: 1¾es ~ rsM-shhanol = 25: 5: 10 analog 3s i ~ spiei 1. oil.

IR spectrum (methylene chloride): 0H 3200-2500 cm 1 (under NHj) 2 \ Ηλ 3430 + 3330 cm "1 20 Cïï2 2540 cm“ 1 K-alkyl 2800 cm 1) '-1 ^ 0CH, 2830 cm J -1 C ~ C 1580 -f 14 30 cm ö7 = spectrum (ethanol): * \ max. 230 nm (0.53; shoulder) 25 245 nm (0.54) 2S8 nm (0.14).

Example 42 1- (4- £ mino-3,5-dichlorophenyl) -2- / Iî- / 2- (4-methoxy-pberoxy) - ät ^] ^ “methyl5 £ pino /“ äthar5ol _ ... "..... _ 30 Made from 4'-amines-3 ', 5'-dichloro-2- / N- / 2- (4-methoxy-phen-cxy} -ethy ^ -mothylami"? J -acetcphenen and Matriur.hcrhydr id in - 52 -

Tetrahydrofuran: hTar ser: Methanoï «13: 5: 3 ar. alog 3: -. 1 si 1. 91.

IR spectrum (khylsnohlorid): CH 2200- · 3500 ém ~ 1 (• -ter NH?) 24: 0 + 3350 cia 1 5 CH2 2940 cm “1 N - alkyl 2790 cm 1 -. 0CH3 2330 cm "1 OC 1530, 1505 + 1485 cm" 1 C-C-Atyl 1250 cm 1 10ü7 spectrum (ethanol) ï% rxx. 230 nm (0.32? Shoulder) 244 rja (0.26; shoulder) (J 254 nm (0.12).

geisp5.el_4 3 1- (4-Amino-3,5-ôichlor-phsnyl) -2- £ ï- £ 3- (4-rethoxy-phenyl) -pso-15SÜ -smino / '- propanol- (1) _ -

Made from 41 -Aiaino-31,5 '-âichlcr-2- / lî- £ 3- (4-metàoxy-phs- · nyl) -propyl / -antinô7-propic-pher * on une triur.ihorhydrid analog

Example 1.

S chm «ls point of the I-Iy drock lord * s ï 201“ '02 ° C (S; rs.).

0 20 Example 44 1- (i "irÀno ~ 3,5" -dichloro-pîienyl) -2- £ 0- / 3- (i-crathoxy-phenyl) -pro-pyl / -2-propylaainQ / -âthanol ^ m ^ ............

.y,

Made from 4'-Ajaino-3 ', 5 * -dichlor-2- / jî - / _ 3- (4-methGxy-phenyl) “propyV ~ 2-propyXamino / - ic c? c-ccd :: - te; ’. ** - '. horhydride 25 analogous to example 1. 91.

-1 IR spectrum (methylene chloride): GH 3b00 cm ΪΓΗ- 3400 + 2490 cm "1 1 -1 0CH3 2% s0 cm CV spectrum (ethanol): rr.ax. 243 nm (0.13) 30 ^ 230 rm (0.03) ~ m. (0.03) l ··· 3 1 _ -

- J J

Example 45 1- (4-Amino no-3,5-dichlorophenyl) -2- ^ N- {Z- (^ nethc ^ y-phenyl) -propy £ 7-ethylamine 7-ethano_l_ __ _____ ^ _____ ________ _

Made from 41-amino-31.51-ichlor-2- / N - / _ 3'- (i-methoxy-phe-: - 5 ny 1> -propyl / -ethylamino / -acetophenen and sodium horohydride ana log example 1.

IR spectra (methylene chloride): OH 3 SCO cm 1 KH- 3335 + 3430 cm "1 z ~ i 0CH3 2830 cm y_i 10 OV spectrum (ethanol) s" S mas:. 243 nm (0.13) 230 nm ( 0.04) '00 rm (0.04)

Bsisciel 46 1 “(4-ίύ &ηο-3; 5-dichloro-phenyl} -2- / K- / 3- (4-methylene-phenyl) -15 propy.l7 ~ r-rc» pylertinp ./- ëth ?. riol _ _ r_____________

Made from 4 * amines-3 *, 5, "dichlor" 2- / N - / 3- (4-iriethoxy "-ph £ -nyl} -prc.pyl7-pr * cpyla: aino? * '£ cet -cph2.ncn and sodium hoxhydride analogous to Example 1. oil.

/ λ IR spectrum (methylene chloride): OH 3600 cm 1 J 20 NH, 3335 + 3495 cm "1 1 -1 OCH- 2EoO cm ÜV spectrum (ethanol): \: ax. 245 nm (0.10) 2SO rm (0.03) 200 r, u. (0.03) 25 Example 47 1 "(4-amino-3,5-dichlorophenyl) -2- / N- £ 3- (i-mnsthcxy-phenyl) - prc-gyj7-cyciomromyl £ mlr; o / _______ __ ^ ^ ....................

Made from 4 * -amino-3 ·, 5 * -dichloro-2- / N- / 3- (4-ißethcxy-phenyl) -prn-pyl / "Ci'elcn." C ": yla; rilr. c7 "£ C ·: in rh-sren and Nat rivrborhydrid /

U

_ ~ M _ analogous to example 1. Oil.

IR spectrum (methylene chloride): CH 3590 caT1 NH2 3395 + 3435 ca ™ 1 0CH3 2550 ca ”1 5 uV spectrum (ethanol): X ~ ax. 245:.: - a (0.12) 230 na (0.04) 300 na. (0.04)

Example 48. r - \ 1 = * (4 ™! niino-3,5-dichloro-phsnyl) -2- £ n- £ 3- (4-msthc: sy-phsnyl) -pro- 10 iy ^ l / ^ ei. hv, l £ aino / -? rcoanol- (1), isomer B _____________________

Made from K- £ 3- (i-methorcy-phsnyl) -propyl / -r.athylâain, 4 * -eanic "2-brca" 3 ', 5 * -cichicr -prcpiophencn, triethylamine and sodium borohydride analogous to example 2. oil.

IR-Spectmia (methyl en chloride): OH 3600 + 3630 cm 1 15:; h, 3390 2490 cm ”1 -1 0CH3 2S35 * 22 40 cm

Aromat 1510.1535 + 1610 cm ”1 W spectrum (ethanol): ^ max. 246 nm (0.14) 27S nm (0.03) 20 2S5 µm (0.08) hj) 300 cm (0.08) MMR spectrum (CDCl ^ / B ^ O): signal of the proton at the carbon atom 1 of Propanol portion: Dubiatt at 4.1 ppia (u = 10 rz).

Example 49 - ·· 25 1- (4 ~ lminc ~ 3, 5-dichlor-pb -2 '£; «· / 3 ·· (b" ithcry-crbanyl ·} -propyl / ~ ^ stIr / l £ mino / -cropanol- (1), isomer Ä

Made from N- £ 3- (4-flour cxy-grer.yl) ~ * prcpy] / - nsi.hy2amin, 4 '-ILminG ~ 3', 5 * -di chlor-2-brcm-? Ro? IC ' pk3: ior., triethylamine and triturate borohydride analogous to Example 2.

/ s - 55 -

Melting point of the hydrochloride: 178-181 ° C.

EMl-Spsktrua dar Basa (CBCI3 / D2O): signal that the proton on carbon atom 1 the propanol part: Duhlett bai 4.6 ppm (J = 4.5 Ez).

Example 50 5 1 »(4-amino-3,5 '= - dichlorophenyl) -2- / N- / 3- (4-ethyl-phenyl) -propyl7-ne fchylamin0 / -ethanol

Esrgastsllt ans 4 * -Ardno-31,5'-öichlor-2-bromo-acetophencn, 1- (4-Äthcny-phsr.yl) “3-methylaïïiino-propaii-hydrochloride, triethylamine '' ~ J -aad lîatriumborhycirid analogously to example 2. oil.

10 IR spectrum (methyl chloride): OH 3590 cm 1 KH2 3335 + 34 35 cm ™ 1 K alkyl 2300 cm "1 W spectrum (ethanol):" X ras. 245 na (0.13) 280 nm (0.04) Λ *; .15 300 nm. - (0.04)

Example 51 1- (i-imino-3,5-dichlorophanyl) -2- / K- / 3- (4-benryloxy-pfcenyl) -prGpyl7 ~ ^ ethyl5mino7-ethanol o

Provided .ans 4 ^ :. 1.100-31.51 -dichlor-2-broa-acatophenone, 1- (4-20 benzylory-phanyl) -S-zasthylamino-propar. hydrochloride, triethylamine and cerium borohydride analogous to Example 2. oil.

IR spectrum (methylene chloride): OH 3590 cm 1 3325 -r 3455 cm "1 1. -1: _ -:> hXky 1 2 53 3 cm, ^ - 5β -

Example 52 1- (4-Ä! AlnO "3" iodine "5-fluor" pfcenyl) -2- ^ 15- ^ 3- (4-m3i ± 02 ^ "*? Hsny 1) -propyi7 ~ rosthylaminp / -at ? mnol ........._

Manufactured to 4 * -AjTiino-3 '-jod-5' - fl \ ior-2-broa-acetopheaon, 5 1 - (4-methosy-phenyl) - 3-mathylemino-propane-hydrochloride, triethylamine and sodium hydride analogously to the example 2. oil.

lR “Spîktrusi (plastic chloride): OH 3590 cm 1 KH2 3235 + 3435 cm" 1 N-alkyl 2300 cm "1 10 Example _ 5 3 [1“ {4 “Ä.mino-3-cy £ ri“ 5-f lucr -phsnyl) - »2- £ n- / 3- (4-mathoxy-pheny1) -pr onv Î7 ~ 2-pr opy laialng / - athanol - '* Made from 4'“ Anä.na-3 * -cyan -5 * -fluoro-2-bromo-acatophenone, 1- {4 “I-" eikC5: y ~ phsnyl) -3 “(2-propyl =: rdno) -propane-hydroehlorid and * 5 Kstriisibornyarid analogously to Example 2. Oil .

IS “Spsfctrum (plastic chloride): OH 3600 cm 1 NH2 3335 + 3435 cm“ 1 CCH3 2330 cm ”1 \ J N-alkyl 2300 cm” 1 20 Csl5 2220 cm ”1

BeljioiGl 54 1- (4 ~ Αι · ίηο ~ 3,5-dichloro-p! V?: Iyl) - 2- / 15- / 3- (2-γλ e thc xy-pkeny 1) -pro- £ yl / {£ n ^. ^ I;:> 7 ·; · n blaepol ”hv tochlcnid v.

Made from 4 1 -amino-31,5'-dichloro-2-brora-acetophenone, 1 - (2-25 Ketkci: y “pke: ryl) -3-m eihyla: * ino-? I ip-an-hydrochloride , Tri 1 tky 1? _Τάη and operation ·; - .; npärid analogous to example 2.

Melting point: from 75 ° C (with sintering).

/! > - 57 -

Bsis ^ isl 5 * 5 1- {4-Aiïiir * o- 3,5-dichXor-phsnyl) -2- £ Κ- £ § · * {3,4 ~ dî: no thc: 4y ~ pfeciiyl) - propyl / ° Kisthyla3iiino7 ~ ethanol _____ _ _ _ ^ _________

Hsrgs prepared from 4'-amino "3 *, 5'-dichloro-2 ~ bromo-ac3tophauon, 1- \ - 5 (3,4-dimetboxy-phenyl) -3-methylamino" propane hydrochloride, triethylamine and Ksfcriumborhydrid analogously to Example 2 .

IHrSpefctrsa Chs.thylanchlorid) ï CH 3600 cm 1 NH- 3390 + 34S5 cm “1 v_i 2 -1 0CH3 2330 cm 10 K-Alkyl 2500 cm“ 1 5-sispi_el 56__ 1- (4-Äminc-3-chloro-5- fcrifluormsthyl-pfcenyl) -2- £ K- £ 2- (4-mstho xy- chsnyi) -gth ^ l ./- asthyl & minQ7 "§thanol

Eergs made from 4 '-Airdno-3, -chloro-5, -trifluoromethylr2- ^ NJ £ 2-15 {4 "m-3thoxy" phenyl) -athy3y-msthylamino7 "acetophenone and cafcrium- • liU-iliydrid in SOSigem methanol analogously to the example 1.

iR-Spehtruia (Kethylenchlorid): OH 3600 am 1 NH- 3410 + 3510 cm “1 2 -1 N-Älfcvl 2800 cm - 20 0-C3- 53ΞΟ cm 1“ 1 alinéat. CH- 2Ê50 + 2940 cm 2 -1 CC 1630 cm üV-Spsfcfcsvsa ui-hanol): k 225 rn (0.33) 244 nm (0.34) 25 280 nm (0.07) 307 nm (0.10) - 53 - 3 -: - / L v-'i.al 37_ {4-Amino-3,5-dichloro-phsnyl) —2- ^ N— £ 1- (4 -nethoxy-phsnyl) - * ^ γο-

Made from 4 * -Aiaino-31,5'-dichloro-2- / Ν - ^ - (4- * înethoxy-v '5 phenyl) "propyl7" ä ^ i- ^ o7' * acatophenone and sodium hydride in $ 0% - igam ethanol analogous to example 1.

Melting point of the hydrochloride: 185-186 ° C (Xthanol / Xthar).

Example 58 _ 1- C 4- & sino-3,5-dichlorophenyl) -2- £ N- (3-phsnyl-propyl) -2-propyl-10 £ ^ iino7 "3th £ nol-hydrochloride _________

Ssrgoshsllt from 4'-amino-31.5 * -dichlor-2-bromo-acetoph-2non, 1-fiienyl-3- (2rprcpylamirto) propane hydrochloride, triethylamine and; Harriuiiiborhydrid analogously to Example 2 ..

Selrasl track: 124-12S ° C.

15 Example 59 1 - (4-ÄtiinO "3,5-dichlorophenyl) -2- / N- / 3- (4-fluorophenyl) prepyl / msthylsisina7-Sfch & nol-hydrochloride orid

Made from 4'-amino-31.5 * -dichlor-2-bre3i-5CStc? Hsnon, 1- (4-? Luor-phenyl) -3-insthyla.T: inc- * p; p '; - y. ? .ri "hycIroch.1orid, ïrilthyl-20 aiain and Hatriinrhorhydrid analogously to Example 2.

Melting point: 185-18S ° C (dec.) Tr

Example _y0 1- (4-Arrdno-3,5-dichlorophenyl) -2- ^ lï- / 3- (i-hydroxyphenyl} -1- s? Ethyl-pgoçyî7-aain! Ô7-gthanol __________________ .. . _ _ 25 Manufactured from 4 '- & ainc-3 *, 5'-dichloro-2- / 5- / 1- ("" hvi uh 3-nyl) -1-methyl-propyl / -aiBino / -acetophenone and Katriumborohydrid in Γ? / *. r \ ky''rof rran analogous to Example 4 ″.. 5s Blusions- - 59 - a mixture of dichloromathan / kethanol / kcnz. Ainr.oniak = 19: 1: 0.05 is used.

. (Oil: 1: 1 mixture of the diastereomeric racemates).

_ -. - ïR ~ spectrum (K3r): OH 2300 - 3500 cm 1 (brown, associated) 5 m2 3460 + 3370 cru “1; CH2 2920 + 2360 cm ™ 1 C = C 1580, 1510 + 1480 cm ™ 1 ÜV spectrum (ethanol): ®ax. 244 ma (0.28) 280 ma (0.08); I 10 300 κη (0.08) UV spectrum (ethanol + Κ0Η): ^ max. 243 nm (0.54) 299 nm (0.15)

Example 61 ^ 1 - (4 "Amine-3,5-dichlorophenyl) -2" £ N- / 3 "(4-xnsthcxy-phenyl) -1 - '- 15 methyl-propyiy ~ aminö7 ~ §thg. nol

Made from 4 * -amino-3 *, 5 * -dichloro-2- £ »- £ 3- {4-methoxy-phs-nyl) -1-methyl-prQpyl / -aminc / -scetophenone and sodium borohydride in aqueous tetrahydrofuran analog Example 4. Oil.

The compound is present as a 1: 1 mixture of the diastereomeric Raes-cj 20mata.

IR spectrum (methylene chloride): OH 3500 cm 1 NH, 3450 + 3330 cm “1 1 -1 CH2 23rO cm 0CH3 2830 -cm“ 1 25 C - = C 1380, 1510 + 1485 cm “1 ÜV spectrum (ethanol ): \ hiîx. 244: m (0.23) 230 nm (0.03) 300 nm (0.09)

V

Example 62 - 60 - 1- (4-aiaino-3-cyan * -5-fluoro "phenyl) -2- / N- £ 2 · - (3.4 ~ df: '± A ^ cz? -Z' :: -: - 71.) -_ - "- äthyiy- £ iaino / -athanol-hydrochloride, _______ __

Prepared from 4 * -amino-3'-fluoro-5 * -c ^ an-scetophs.non, Selsn-5 dioxide, 2- (3,4-biinethoxy-phenyl) -ethylsrdn and Kavriauborhydeid 'analogously to Example 5.

Sehnielpunkt: 196-197 ° C (Sers.).

bj Example 63 1- (4 -.% sdno-3-fluoro-5-iodopheny1) * -2- £ N- £ 2- (3, 4-di2 & sthcxy-phsnyl) - 10 §thyl / ^ S :: alnc ^ “athanol ~ hvdyo-; h.1 orld __ _________ _____________. Made from 4’-amino-3'-fluoro-51-iodo-acetophsnon, being! - ΐ -. csxid, 2- (3/4 “direthoxy" pba :: jl) i * äth.ylc ~ in and Natrirrnborkydrid I 'analogous to Example 5.

; ·. Melting point: 1S2-193 ° C (ser.) *

J

: 15Example 64; i 1- (4- £ iaino- 3-chloro-5-fluoro-phenyl) -2- £ K- / 2- (3,4-dirt-athc-sy-O plisnyl) ~ ethyl7 ~ ainino7 ~ §thanol ~ hydgochloride \, Herçes-tellt sus 4 * - £ jûino-3 * -chlor * -5 '-fluoro-acetophsnon, Selen- | dioxide, 2- (3,4-disethoxy-pheiiyl} ethyIcmin and natriuraborhydride 20 analogously to Example 5.

* Sklrüelxpunkt: 1S4-136 ° C (Z-srs.).

Example 65: 1- C4-Amino-3-bromo-5-f lucr ~ *; - ha :: vl) -2 “- /” * -, / 2- (3,4-dir ethp ^ -tÄe-

H

| nyl) "äthyl / ^ sp inq / - äthanol-hyd roch lor id_________________ | 25Hs made from 4'-ardno-3 '-bross-51 -fluoro-acetophenone, being! -! cxid, 2- (3,4-dimethcxy ~ ph ~ ay 1} · · = tby and :: sürlu Innig du: d - 61 - analogous to example 5.

S chine 1 point: 194-195 ° C (2 ars.)

Example 66 1 "{4-Amino-3-fluoro-5-cyanophenyl) -2- / 11- / 3- (4-raathoxy-phenyl) -5 propyl I ^ aialno7-ethanol ^ __ ___________________

Prepared from 4, -amino-3, -fluoro-5, -cyan-acetophenone, selendi-oxide, 3- (4-Hathoxy-phenyl) -propylaaiin and Hatriusiborhydrid aru-log Example 5.

0

Melting point: 119-121 C.

10 Example 67 T— (4-Audnc-3,5-dichlorophenyl) -2- / N- (3-ph eny1-pro py 1) -aiaino / -gthgnol-hydrochloride _ _ _ · _ <· _ _ , _______

Made from 4 '-isinc-3', 5 * -dichlor - ?. eetc-phe.non, be andicxid, 3-plienyl-propylaissin and sodium borohydride analogously to Example 5.

15 Melting point: 130-181 ° C (Tsars.).

Example 68

O

1- (4- * i2inc-3-chloro-5-fluorophenyl) -2- / N- (1 -methyl-2-phenoxy-ethyl) - £ P.ino / -§thanol-dihydrochloride

Made from 4'-aaino-3 * -chloro-5'-fluoro-acetophenone, selenium. 20 dioxide, 1-liethy 1-2-pheno ^ ry-athyI-min and sodium hydride analogous to Example 5.

Melting point: 158-160 ° C (dec.).

/ / - ¢ 2 -

Beispiel_69 I- (4-Æ.mino-3-cyan-5-fluorophenyl) -2- £ n- (1-i ^ lhyl-'2 ον, ".roxy-ethyl) ~ aminep7 ~" thanol-hyd ? / ochlogid

Prepared aas 4 '-Sjnino-3' -cyan-S'-fluoro-scetcphenon, Selsndi-5 oxide, 1-Methyl-2-phenoxy-Etliylc3'd3i and NatriiiBborhydrid analogously to Example 5.

Melting point: 173-1 S4 ° C (ser.).

Pi Example 70 1 - (4-JLaino-3-broia- 5-fluGr-pheny1) -2- ^ îî- (l-rsihyl-Z-phsnoxy-10 «thyl ^ gglgo / ^ th? Nol-dihydroch ·! C -rid __ __

Made from 4 * -ArrdriO-3 '-bros-S' -f luor-scetc-phsnon, selenium dioxide, 1-Meihyl-2-phenoxy-SthyI? "In and! * 3triirnbc-rhydrid analog = example 5.

Schiaelzptmkt: 136-15S ° C (Sers.).

15 Example 71 K- ^ 2- (4 ~ Anii.no- 3,5-dibrcn-phs.nyl) - £ thyl / -N- / 3- (4-rüe thoxy-phenyl) -0 propyl / -methy laiain ___

Ksrgeshellt from 4- & ΰ ± ηο-3,5-dib_c: a-l '- ^ 3- (4 ~.;. T-theccy ~ phanyl) -pro-pyl / -N-iaethyl-phenylacetic acid £ -aid and Lithiusalua & niunihyärid ΡΠ analogous to example 7.

Scfenelsp-unfct of the hydrochloride: 141 «Ir-S ^ C.

Example 72 II- / 2 ° {4 ”Arinc - 3,5-d.ichlor-v-hsry 1) -öiiyl / rr - / 2- {4-rtethcxy-pbe;: y .1) - propy 1 / - :. 1¾thylnniin _ _____ __ __............

^ 5 Prepared aas 4-A.jrdno-3,5-di chlor - "- / 3- (4-neth.CMy-ghenyl) - -63" / propyl7 ~ N-aathyl "phsnylessigsäureamid and LithiumaliuniniiHiIiydrid analogously to Example 7.

SchiaaIpunkt the hydrochloride: SG- 54 ° C.

Example 73 5 N- / 2- (4 "Änino" -3, 5-dichloropheny1) -ethy ^ -N- ^ Z- (4 ^ sthcsy “phenyl) - ät hy l7-Rie t hy 1 am in. .............. _ _ _ __ ________

It consists of 4 "£" Inc-3,5-dichloro-N- £ 2- (4-msthoxY-phsïiyl) - Ethy ^ -îî-nethyl-phanylass.igsMureaaid and Lithiusaluiäiniuashydrid analogous to Bsispial 8.

10 IU spectrum (cathyl chloride): NHj 33SO + 3470 ca 1 N “alkyl 2780 ca 1 0CH3 2830 ca“ 1 aliphatic. CH, 2850 + 2930 cm “1 1 -1 C - C · 1510 ca 15 ü7-S? Ektruia (ethanol): \ msx. 245 na (0.24) 281 na (0.03) 305 na (0.07) • Bslsolei 74 ON “£ 2" (4-amine-3,5-di chlorophenyl} -ethy Ϊ] -1Ζ- / Α- (4-asthcxy-phsnyl) - 20 butvÎ7-5! 31hv.lanin __________________

Made from 4-Airdno-3,5 "dichloro ™ N- £ 4- (4-matbexy-phsnyl) ~ butyl7" N-methyl "phenylacetic acid and lithium lithium hydride 'analogous to Bsispial 8.

IR spectrum (cathylene chloride): UH, 3320 + 3480 cm “1 ^ -1 25 OCH, 2330 approx ^ -1. CH, 2850 + 2930 cm "" 1 :: h '2100 - 2500 ca "1 C = C 1 S-.0 cm UV spectrum (ethanol): * X max. 245 ma (0.22) 30 280 na (0.01) / :: i na (0, -Cc)

Example 75 - 64 - / * K "^ 3" (4- £ iaino-3,5-dichloropheny 1) -propyl / ™ 2 "(3,4 ~ df rvathoxy-phe-nyl) -ethylamine ~ hydrochloride. id ________ ^ __; "Prepared from 3- (4-amino-3,5-aichlorophenyl) -3- / 2- (3,4-diissth-5 oxyphenyl) ethyl ^ propionic acid amide and lithium aluminum hydride * as in Example 7.

Melting point: 142-145 ° C.

A

tp

Example 76 N- / 3- (4 “* kïïiino-3, S-dichloro-phsnyl)” propyl / “K- / 2" - (3,4-öinsthoxy-10phenvl) “äthvV-inethylainin ________.: Made from 3 - (4-As: ii? .O ~ 3,5-öi'chlor-phe.iyl) -N- £ 2- (3,4-öiineth ”© xy-phsnyli-äthy ^ -K-raethyl-piopionsciureamid and Liih.iur.alu-miniimhydrid analogous to Example 8. oil.

IR spectrum (methylene chloride): NI ^ 3400 + 3500 cm 1 15 OCH, 2835 + 2360 a “1 3 -1 NCH, 2d00 cm

Aromat 1510 + 1590/1615 cm 0 UV spectrum (ethanol): * Xmax. 239 nm (shoulder) 281 nm (0.11) 20 500 nm fo, C3).

Example 77 N- £ 3- (4 ~ Ämno-3 "brom *" phsnyl) -p2 c-pyl / -2- (3,4 "dimethc.-cy -phenyl) ethylamine hydrochloride ___

Made from 3- (4-An & no-3,5-dibromo-phsr.yl) -N- / 2- (3,4-dinar.h “p 5 - cxy-phsny1) -athy 1 / -propienamide and Li thiunaluminiumhy erid analogous to example 7.

Melting point: 131-134 ° C.

/ / »> - 65 -

Example 73 K- £ 2- (4- £ îaino-3,5-dich! Or ~ phenyl) ethyl / -N- / 3 ~ (4 ~ hydrcs: y "p! Vsny!) -1-methyl-propyiy -amin _ '. Made from 4-Amiuo-3r5 "dichloro-N- / 3- (4-» hydroxy ~ phenyl) -Ί-5 s * ethyl-propyl / -phenylacetic acid? jnid and Lithirr'al'riiiiiir.ühydrid in tetrahydrofuran analogous to Example 8. See the chromatograph

Cleaning is carried out by means of medium pressure chromatography on KiessX gel (SorncröSe: 0.015 - 0.025 mm) with polyethylene chloride t methanol: fconz.Ammoniak = »13: 1s0.1 as eluans. Foam.

'(i ~ 1 10 iE-Spsktroa (liethylenchlorld): OH 3580 cm KH, 34SO + 33S5 cm “1 1 -1 CH2 2920 di C * C 1530, 1510 + 1480 cm" 1 UV spectrum (ethanol):% siax . 24 2 na (0.24; shoulder) 15 - 280 rm (0.07) 303 na (0, CS) GV-Spumtrum (ethanol * KCn): r; ~ x. 242:.: 11 (0.53 ) 300 m (0.16).

Baas ciel 79 C) 20 S ”/ 2“ (4-Äirdr) o-3, S-dichlorophenyl) ethyl / -N- £ 3- {4-iriethozy-phenyl) "1 ° msthyl-pgcgvl / ~ gmin ^ ... ________ ii

Made from 4-asinc-3,5-dichloro-N- / 3- {4-a5ethc »: y-phenyl) -1-®2thyl ~ propyl / ~ phenylacetic acid aiid and Lithiu ^ alrminiu-iiydrid | In tetrahydrofuran analogous to Example 8. Oil.

; "25 IR spectra (Ksthylenehlcriâ) s: -7H ~ 5 50 *: · 3 5¾5 cm 1 ^" 1 CH cm 1 -1 I OCH. 2830 cm 3 "1 C = C 1550, 1510 -5- 1435 cm; ; 07 “Soekt2um (ethanol) s ^ .rax. 242: ri (0.25; shoulder)

! l BO

I J 250 ma (0.07)! J / 302 nm (0.08).

Example 80 f - 66 - N- £ 2- (4-amino-3,5-dichlorophenyl) -athyl7-N- / 3- (i-bansyloxy-phenyl) "propyl /" Siethyl £ ïïiin ^

Made from 4-amino-3,5-dichloro-N- / 3- (4-bsnzyloxy-phenyl) -5 propyi? -N-methyl-phenylacetic acid «atid and Lithiuiaaluminiuiûhy-- drid analogously to Example 8. Oil.

IR spectrum (methylene chloride): NH2 3330 + 3490 cm ^ N-alkyl 2 300 cm-1 / 'n üv ^ Spsptrm (ethanol): \ max. 245 nm (0.10) "230 nm (0.04) 300 nm. (0.04)

Example 81 N- (2- (4-Amino-3,5-dichlorophenyl) -ethyl / -N- / 3 "(3,4-dimethoxy- '' phsayl) -propylZ-ethylsjain __ _ ♦ _; * > 5 Made from 4-amino-3,5-dichloro-K- 3- (3,4-Qi: r, sthcxy-phsnyl) -propyl / “N“ Ssthyl-chenylessiçsaur-32Juid and Lithiunalîrrdriiuüihy-drid analogously to Example 8 oil.

-1 ! R spectrum (methylanchloride): 3355 + 24S5 cm Ο. OCH- 2830 cm-1 20 N-alkyl 2800 cm W spectrum (ethanol): \ max. 230 nm (shoulder; 0.13) 245 ira (shoulder; 0.12) 282 nm (0.04) 302 nm. (0.03) N ~ / 2- {4-ÄainO “3,5-cichloZ“ pbenyl ) ^ ”Thyl7o: - / 3- (2 ~ r; eihcxy-phe- & yl) ° P £ Qpy? Y ^ ethy lamin-Inf drochlc-r 1 d ____

Prepared from 4-amino-3,5-dichloro-N- / 3- (2-nethoxy-phenyl) - - 67 - * propyl / “N-methyl-phenyleä3igsäuresjaid and lithium aluminum hydride analogous to Example 7.

Point: 160-164 ° C.

L.

Example 83 5 N- / 2 “(4-Aluino-3,5-dichlorophenyl) ethyl / -N- (3-phenyl-propyl) ~ - - methylamine

Made from 4-. £ minc-3,5-dichloro-N- (3-phanyl-propyl) “N-msihyl-ί phenyiessigs§ur eamid Li thirsalscainiusihyöriä analogous to! game 8. oil.

IQIR spectrum (ethylene chloride): NH2 3390 + 3430 cm 1 | N-alkyl 2800 cm 1 '| lT7 "spectra: m (ethanol):% nax. 145 nm (0.12)! - 300 ïim. (0.03) - »*! - "Example 84 15 M- £ 2- (4-Airdno-3,5-dichlorophenyl)“ ethyl / -N-J / 3 ~ (4-nethoxy-phenyl) propyl / ”amine ~ hydrochloride ___________ __________________

Prepared from 4-amino-3,5-aichloro-N- £ 3- (4-ethoxy-phsnyl) -0 propylj-phenylacetic acid amide and Mthiumalinrdniirnhydrid analog

Example 7.

| _ 20 melts * .nkt: 203 ~ 205 ° C.

! '~ Example 85 K IÏ-ß- {Ι-1-.ïài.TiO-3,5-dichlorophenyl) -Sthyi? -11- / 3- (4 --.-. Ithexy-pksnyl) * j' pr opy Γ7 - cy c 1 Qp r opy 1 am ln ______ _______ _________ __ _________ i | Bsrgestsllt ans, 3-d me? or-N ~ / 3- (4-msthcxy-phenyl} - ii ^ PpiOpy V-Ih-oy clep-ropy l ~ pl s.r / lλ ~ higsSuraardd and Lithimalminirr * l hydride analogously to Example 8. Ql.

Jj IR spectrum (methylene chloride): NH2 3390 + 34 90 cm 1, j, ocsu 2330 cm ”1 y UV spectrum (ethanol): \ max. 245 nm (0.15) 250 nm (0.04) 300 nm. (0/05) • V "

Example 86 5 N- / 2- (4-Jüûino- 3,5-dichlorophenyl) -âthyl / -N ~ * £ 3- (4- * m2tàoxy-phe- - '· nvl) -nropyiy-propylêmin _ ___ _ __

It consists of 4-? Jmino-3,5-dichloro-N- / 3- (4 “isetboxy ~ phsnyl) - ^ propy ^ -K-propyl-phenylacetic acid suresmide and lithium alixminine hydride ~ as in Example 8. Oil.

10 IR spectrum (ethylene chloride): NH2 3390 + 3490 cm 1 OCH, 2830 cm ”1 ^“ 1 N-alkyl 2c00 cm UV spectrum (ethanol): \ max. 243 nm (0.13) 280 nm (0.04) -; "» 5 330 mb. (0.04) - -

Example 87 lv- £ I ”(4-Am.iziO“ 3,5-dichlorophenyl) ethyl7 * “K“ / 3- {4-methoxy-phe-

Produced at 4-Απ1ηο “3,5-ά1οΙιΙθΓ-Ν -, / 3- (4-zaathoxy-phenyl) -pj: opyi7-iî-gthyl ~ phenylassiçs« ur9 = nid and Lithiiœaluminitsahy-drid analogously to example 8. Oil.

-1 IR spectrum (methylene chloride): NH, 3390 + 3490 cm ά _ -1 OCH, cm H-alkyl 2300 cm “1 25 W spectrum (ethanol): \ m ex x · 243 nm (0.13) 280 nm (0.04) Λ 300 nm. (0, C4) - 69 - i

Example 88!? - £ 2- (4- & rdao-3,5-dichloropheny 1) ~ âthy 1 / -13- / 3- (4-mathcxy-pheny1) - pyo? Yl7-2 "per ^ vl £ iûin ______

Made from 4-ô_rîiiïio-3,5-dichlor “N- / 3- (4-jssthoxy-phenyl) -5 propyl / -! Γ {2 “propyl)“ phenyl3ssigsâiir? -R, rdid iind lithium aluminum hydride analogous to example 8. Oil.

"1 IH spectrum (Kethylanchlorid): 3390 + 3490 cm 0CH3 2830 cm" 1 W-Spskirum {Xths.no!): "V pax. 243 nm (0.13) 10 280 nm (o, 04) 300 nm ( 0.04) * E5.ts0.iel 89 l \ “/ 2“ (_4 “ΑΐΓίϊηο-3 r5 ~ dichlorophenyl) ethyl / -N- / 3- (4-ethoxyphenyl) - propyj.7- aathy3 amine ____ ^ __ _ ii <n l_______ _________ _

Manufactured to 4-ij & ino-3,5-ôichlor ~ N- £ 3- (4-Ifchcxy-phsnyl) -prc- py £ 7- N-methyl-ph envies siçs-Mureamid and lithium aluminum hydride analogous to egg & piol 8. Oil.

Il ^ rSz- ~ .ktr.vû (iâethyl-enchlorid) ï NH, 3390 + 3490 cm 1 ^ —1 Π 0CH3 2830 cm 20 K-Alkyl 2800 cm-1 y7-Spättrm (££ 1 *** 1101): \ ry * x. 245 ïim - 0.12) 230 nm (0.03) 300 nm. (0.04) A Example 90 25 îî- £ 2- (4-2Lmino-3,5-dichlorophenyl) - Sthyl / -K - £ 3- (4-methcxy-pheny2jp Ip ^ ethyl-pronyl /pmst.hvl?sd n __ _____.....

Eergs adds 1 -Xthoxycarôonyloxy-1 - i4-amino-3, S-diehlor-phe-nyl) “2- / N- / 3- (4-methoxy-pheny 1) -1 -rr.-sthyl-propyl / - methylaiiiino / -

Ethan mnd Îïstr ± -am? Oo.thyärid in Isoprcpanol analogously to Example 9. Ol.

- 70 »IR spectra (methylan chloride): NH2 3 4 SO + 33SO cm 1 CH2 2930 cm” 1 N-Alkvl '2790 cm 1 OCH. 2340 cm ”1 - r J -1 J C-C 15-30, 1510 + 1480 cm

Example 91 N ~ £ 2 ~ (4-AiüinC “3“ brom "5-cys: n-phsriyl) -ethyl / -N“ / 4- (i-msthcxy-phenvl) -bOtylZ-Sathylsaln r 'J Made £ ” s I-Äthcxycarbonylcxy-1- (4-amino-3-hrom - 5 - cyan-10 phenyl) -2- / κ- £ 4- (4-mathoxy-phenyl) -butyl / -meäiylamino / -äthan isd Sodium ruby hydride analogous to Example 9.

Analysis:

Bar .: C 60.6 H. 6.3 Br 19.2 N 10.1

Found: 60.5 6.1 '19.2 10.1' 15 Example 92 IÎ- / 2 “(4-amino-3-chloro-5-cyano-phsnyl) -Syl / -N- ^ 2- ( 4-jßethcxy- pheayD-a ^ yl7 "m ^ chyl amtin Q Made from 1-sthxxycarbonyloxy-1 - (4- * amino-3-chloro-5-cyan-phsnylÎ- -laethoxy-phsnyl) -äthv 1 / -methy lasiino7-Sthan 20 md Hatritnljörhydrid analogously to Example 9.

IF spectrum (methylene chloride): hH. 3400 + 3490 cm 1 z -1 N-alkyl 3790 cm 0CH3 2330 cm ”1 - - alignai. CH_ 2850 d 2940 cm 1, '25 CseS 2210 cm C-C 1620 cm ”1 UV spectrum (xthanol): \ max. 244 nm (0.26) 230 rm (0.04) 335 nm (0.15) lsm \ - 71 -! .tel 93 i i! {4-Äsiino-3 "broai ~ 5-cyan-phenÿl) -ethyl? -N- ^ 3" (i-ast & oxy-pha- .-: yi) ° pgopy3 ^ 7-raefchylamine * Made from 1 -Xthcxycarbonylcsy-1 - (4-smino- 3-bromo-5-eyän- 5 pheny 1) -2- ^ N- ^ 3- (4-roethoxy-phsnyl) -propyl7- & athylaiiiinç7 “& tli & ri and îïatriumbûrhydrid analogously to Example 9.

'IR spectra (methylene chloride): NH2 3390 + 24SO cm 1 N-alkyl 3790 cm 1 0CH_ 3830 cm "1 J -1 y ->. 10 aliohat. CH- 2850 -i- 2S40 cm ^ Λ C ~ N 2210 cm C = C 1620 cm “1 07» Spsktwm {Xthanol):% uax. 244 nm (0.2); 2S0 nm (0f04) i - 334 rail (0.13).

l ·:: I ’'* Example 94? î KZ.2 "(4-Juidno“ 3 “chlor-5“ Cyan “phenyl) -äthyl7“ ^ “/ 4" · (4 ~ msthosy- 1 :: 4: £ r: vl) '' biîtyl / “' 'ssthvlaiüin _ _____ __ "___ I; ’-“ - "·" ““ “

It is composed of 1-ethoxycarbonylc * xy-1- (4-amino-3-chloro-5 ”cyan-w phenvl) ~ 2 ~ / β ~ [Α ~ {i-nethcxy-phenyl) -hutyl7-mathylamino / -Ëthan | and Katritr & borohydride analogously to Example 9.

I - Analysis:

Ber. : C 67.5 H 7.3 Cl 9.53 N 11.25 i \ Found: 67.5 7.14 9.65 11, 34 I '-î | 25 Bel sol el ..... 95. _, “J- {4-2j? Ino-3-chloro-5-trifluoromethyl-phenyl) -2- / N- / 4- (4-ms chcxy- | pheriyl) -butyl7-ir> ethylai3inQ7 ~ âthanol _. ]]

Ksrgastsllt sns 4 '~ Λ: Αίηο · -3 chlcr ~ 5, -trifluor :: at: -. Yl'-2 ”£“: - / 4- Ci - λ - 72 - «.sthoxy-phsnyl) -butyl / -33thylamino / -ciCi2tophsnon and Hatriir; bc-r ** hydride in 8% by weight methanol in analogy to Example 1.

-1 IR spectrum (metilylene chloride): OH 3590 cm NH, 3410 + 3510 cm “1 ^“ 1 5 N-alkyl 2800 cm 0CH3 2830 cm “1 ^ alichat. CH- 2850 + 2930 cm 2 -1 aromat. C = C 1630 cm ITv spectrum (ethanol): max. 225 nm (0.32) O 10 245 ™ (0.31) 280 nm (0.06) 308 rm (0.10) w **

Example 96 1 ~ (4-Ami no- S-cyan-ph snyl) -2- / N- / 3- (4-methoxy-phenyl) ~ 15 msthyl & niinp7-ëtha.nol - {J (4-

Prepared from 1- (4-amino-3-bromo-5-cyanophenyl) -2 - / ^ - / ^. s & fchoxy-phânyl) -propyJL7 “r! 3thylamAi'iC / ~ a hhanol in ^

Palladium / carbon and hydrogen analogous to Example 11. ^ IR spectrum (methylene chloride): OH 3610 ®n "i ~ 'on Ä, -5 £ Qö cm 20 RH 2 3400 + r - :: - alkyl t'oo * rra ^ OCH-, 2830: "·· ιΊ - \ aliphatic. CH- 28 dO r '2 - i C == N 2210 3 * 25 oe 16 30 UV-Spsktrcm (ethanol) ϊ issx. 251 nm (0.31) ^ 280 nm (0.6) 1 / '328 nm (0.12).

- 73 -

Example 97 -Amino- 3-chloro-ph.enyl) -ethy1 / -N ~ £ 3 ~ (i-benzyl cxv ^ phsnyl) - propy 1 / -methy 1 am in __

Made from N- / 2- (4-Jünino-3r5-dichlorophenyl) ethyl / -N- / 3-5 (4-bensyloxy-phenyl) propyl / methyl: rdn and hydrogen as in Example 11. Oil.

IR spectrum (methylene chloride): NH2 3350 -J- 34 90 cm ^ N-alkyl 2750 cm ^ o

Example 58 10 n-ß- (4-imino-3,5-dic.hlor “phsnyl) -ethyy-N - ^ - (4-hydrcxy-phenyl) -1 propvjTpm-sthyl am ln ^ ________ _____

Kergestel.lt from 11- / 2- (4-A? AiiïO-3,5-dichloro-phsr; yl} -sthyl / -N- / 3- (4-1fcenzyloxy-phenyl) -propy l / -2aathylemine. And Hydrogen analogous to Example 16. oil.

* 1 - 1j 15 IR spectrum (ethylene chloride): OH 3580 cm -1 NH_ 3390 + 34 90 csa À -1 N-alkyl 2800 cm O Example 99 1- (4-Asiino-3-fluorophysnyl) -2- / 11- {1 ~ ethyl "2 ~ ph-.ericxy '!' Ethyl) -20 amino7-ethanol-tosylate ^ _ ___ _ _ __________________

Made from 1 "(41-icâôa'nin> -3" fl'p :: r-çvcnyl) (l ^ meikyl "* 2-phenoxy) -Styl / -amino-§thanol and Ns triv: ... hydroxide analog Example 17.

Melting point: 124-128 ° C.

/

Example 100.-7 /, - / 4- 1να £ _2 "(4-Aüi.lno-3,5-dichloro-phanyl) -âthyl / -N- £ 3- (4-msthc-xy-phen-cxy) "propy fZ-iaethy lamin_________________________

1/74 g (0.014 mol) of 4-methoxyphenol is dissolved in SO ml of dry 5 tetrahydrofuran, the solution is cooled to -5 ° C. and 0.67 g (0.014 mol) of a 50% dispersion is added with stirring of sodium hydride in oil. Kan stirred for 2 hours at 0 ° C and then added dropwise at the same temperature with a solution of 4.2 g of N- £ 2- (4- & mino-3, S-dichlorophenyl) -Methyl / -K- (3rd - 'J ”” ^ 10chlor-propyl) -methy lamin in 50 ml dry-eia tetrahydrofuran. ·

The mixture is stirred at about 20 ° C. for 18 hours. The reaction mixture is then concentrated in the Vshuuia, and the are? R.pf residues and is distributed between ether and better. Men separates the phases and extracts the aqueous layer three more times with ether. Dis Ί 5 combined ether extracts washed with water are dried and evaporated in vacuo. The oily3 'seed residue is purified chromatographically on a silica gel column (flow agent: ether). After evaporation of the desired fractions, the above-mentioned compound is obtained as an oil.

^ IR spectrum (ethylene chloride): NH2 3390 + 3480 cm 1 CH2 2550 cm "1 0 N-alkyl 2800 cm" 1 C'-C 1585 + 1560 1505 cm "1 GV spectrum (ethanol): \ max. 230 µm (0.18; shoulder) 25 246 nm (0.085; shoulder) 235 mn (0.05). 1 u (y \ j;. -75-- i

Example 101 1- (4 ~ Ämino-3,5-Äichlor-phdnyl) -2 - ^ - (3 ~ phenyl-propyl) “ethylaning? -Ethanol-hydrochloride _____________________________ ___. 2 g 1- (4-Airiino ~ 3 / S-diclilor-phanyl) "2 - / N- (3" ph ~ r.yl ~ propyl) .- s7rii2q7- 5 ethanol hydrochloride are dissolved in 50 ml ethanol. 0.4 ml of acetaldehyde is then added to this 1.5% solution under stirring at room temperature, 1.2 g of sodium cyanoborohydride (see below), care being taken by adding 2N hydrochloric acid to ensure that a pH value of 0 is set and maintained This pK core is stirred for a further 2 hours. The solution is poured into water 10 and unacidified with 2N hydrochloric acid to destroy excess Katriua! cyanoborohydride. Then 2N sodium hydroxide solution is added until the reaction is clearly alkaline 2 times with Ks-thylene chloride, wash the combined cathylene chloride phases with water, dry over sodium sulfate and evaporate to dryness in vacuo to 15. An almost colorless oil remains, which is dissolved in [. Ethanol is acidified with ethereal hydrochloric acid to pH 5. Then the solvents on the red a t ic-r, e verd a, r.p f er removed in vacuum. The remaining oily residue "brought to the Eristsi * · 20 solution in Basicester. Kan receives colorless crystals from the melting point 102-105 ° C.

Example 102 1- (4-ethoxycarbonylaraino-3-cyan-5-fluorophenyl) -2 ~ / n- £ 2- (3,4-I · dimethc? R / -phenyl) ethyl7 ~ 5 ~ ilnoy ”atk ~ nol'w: -7d: -c -.:- 1110: .- 1 d 25 Made from 41-KthcxycarbonyXamino-31-cyan-51-fluoro-acsto-phenone, selenium dioxide, 2- (3,4 “Dii; ; ethoxy-pbenyl) -ethylsmin and I'a- triirsborhydrid analogously to Example 4.

Melting point: 190 ™ 191 ° C (dec.).

j> - 75 -

Example 103 1- (4-Aaino-3-cyan-5-flucr ~ phenyl) ~ 2 ~ / Ν- / 4-- (4-methcxy-pheny1) -buty l / -methy 1 aiaino / - ä t hanoï _________ i__ __

Made from 4 1 "Amine-31 -eyan-5 1 -f lucr-2- £ ï- / 4- (4" Cisuncszy - 5 phenyl) -butyi7-methylai] iino / -aeetGplisnan and sodium borohydride in 80% methanol analog Example 1.

IR spectrum (mathylene chloride): OH 3590 cm 1 -1 NH2 3400 + 3490 cm N-alkyl 28 * 00 cm “1 10 0CH3 2830 am" 1 aliphatic. CH ^ 2850 + 2930 approx. 1 C ..-- N 2210 approx "1 CC 1635 cm" 1 ÜV spectrum (sthanol): * X max. 241 nm (0.27) 15 '.280 Em (0.07) * 322 ra (0.14)

Example 104 1 - (4-Acetamino-3-brois-phsnyl) (4-aethosy-pheny1) -buty 1 / -xae thy 1 am ino / - ë t h a. p ο 1 __________________ _________

O

20 Made from 4 * acetsa? ·? Ο-3 '(4-methoxy-phenyl) -butyl / -methyl £ mino / “ëcctca' .. ancn and 275triorbcrhydrid in 30% igsm methanol analogously to Example 1.

IR spectrum (methylene chloride): OH 3590 cm 1 OH 3410 ca “1 25 ^ **. W. “1 it 'Ί- .. j · J. tV -.Ü Uitl 0C33 2830 ca“ 1 aliphatic. CH2 2850 + 2930 cm 1 arcexate, C = C 1510 cm 1 -1 0 = 0 1 / approx. 30 amide II 1510 cm “1 / /, - 77 --.....

*

Example 105

Racemates A and 3 of 1- (4-A ~ .ino-3,5-öichlor · -phenyl) -2- / N- / 3- (4-hydroxy-phenyl) -msthylyj3ropyiy-methylamlnQ / -ethanol _________ 36 g 1- (4-amino-3,5-dichlorophenyl) -2- / N- / 3- (4-hydroxy-phenyl) -5 1 “iaethyl-propyl / -methyla2aino / -ethanol (1: 1-“ Mixtures of the diastereomeric racemates A and 3) are dissolved in ether and mixed with 0.5 equivalents of 3N hydrogen chloride in ether. The crude crystals of the hydrochloride of racemate A obtained are first crystallized from isopropanol and then twice by dissolving in a large amount of methanol Z'''10 and then evaporating until crystallization begins.

Narrow trace of hydrochloride 243-249 ° C (ser.).

* C-1Ü4R “spectrum of the race (CDCl ^ / CD ^ OD): CH- I 3.

-CH2-CH2-CK- 37.50 îpm CK3 15 -CH -CH -CK- 53.36 ppm Q ^ CH-CH3 13.91 ppm ^ 36.33 ppm ^ N-CH2- 61.03 ppm

OH

l -CH- b 3.3 9 ρρπι 20 The isopropanol see mother liquor is evaporated and distributed between ether and 2N ammonia. The evaporation residue of the dried organic phase is separated from adhering racemate A by means of KPLC to isolate the racemate B {SiO 2 50; \ ^ 73-_

Merck; 0.015-0.025 mm; Ether-methanol ~ 10: 1). The crystalline SindaHipf rests and is uricrystallized from a lot of ether by Ken centers in the boiling heat.

Melting point: 128-131 ° C.

513C "hMR" spectrum (CDCl3 / CD3OD): CH ^ __ -CH2-CH2-CH- 35.61 ρρια CH * lj | 3 -CH2-CH2-CH- 59.21 ppm ^ C3 "CH3 14.56 ppm> N» CH3. 35.03 ppm 10 63.11 ppm

OH

-CH- 69.08 ppm O Example 106 1- (4-Äiaino-3-broïïi-5-cyanopheny 1) -2- / N - /. 4- (4-mathcxy-phenyl) -bnfcyiy -bengyl sminçj -rthanol hydrochloride _. 15 Manufactures sus 4 '- £ ir, ino-3' -lbroir .- »5 * -cys.n-2- £? -, £ 4- (4-msthoxy-phsnyl) -butyl / -benzylamino / -acetop2 ' iemon and KrtriirÄorh.ydrid in 90% methanol as in Example 1.

Melting point of the hydrochloride: 122-126 ° C.

-Ί «_ 79 _

Example 107 1 “(4-Aaino-3-brca-5-cyan-pkeny1) -2- / Î1- / 4- (i-rrethcxy-phsnyl) -bαtyi / -all · yl £ πlllGyCTäth £ nol .._________ ^ Prepared on the 4 '-ainino-31-brc: û-51 "cyan-2- / N" / _ 4- (4-methoxy-5 phenyl) -butyl / ~ allyIsmino / -acetophenone and sodium borohydride in SOSiges methanol analogously to Example 1. Resin.

IR ^ spectrum (methylene chloride): NH £ 3330 + 3490 cm 0CH3 2830 + 2940 cm "1 CN 2210 cm-1 l) -1 ^ 10 aroma. C = C 1610 cm UV spectrum (ethanol)): max. 223 nm (0.43) 244 µm (shoulder, wide; 0.07) 330 µm (wide? 0.05) *; Example 108 15 1 ~ (4-Amino-3-broia-5-cyanopheny 1) -2 -, / 14- / 4- (4-methoxy-phenyl) -butyiy ~ isopropylamine> / - ethanol hydrochloride

Manufactured to 41-24min o-31-ferons.-51-cyan-2- / N- / 4- (4-methcxy- -O phenyl) -butyl / -isoprcpylamino / -acetophenone and natriuraborehydride in 90% methanol analogous to example 1.

20 melting point of the hydrochloride: sintering from 40 ° C.

Calculated: C 55.6 H 6.29 Br 16.2 CI 2.14 N 3.46

Found: 55.3 6.37 15.4 S, 84 8.83 1 - Example 1C9 oia 9m 1 "(4-Ämino-3-broiu" 5-cyan - phenyl) -2- / N- / 4 ™ (4-methcxy-p-henyL) -2 0 bu tv. \ / - n ~ prouy 1 am in oj - 3rd th an ο 1 - hvd ro c here id

Made from 41-amine-31-bromo-51-cyan ~ 2- / N- / 4- (4-methcxy-yi - 30 - phsnyl) -butyl / -n-propyls2iino / -acetophenone and sodium borohydride in 90% methanol analogous to example 1.

Melting point of the hydrochloride: sintering ah 40 ° C.

3. : C 55.60 H 6.29 N 3.46 5 Found: 55.52 6.32 8.39

Example 110 1- (4-Amino-3-bromo-5-cyanopheny 1) -2- / N - / _ 4- (4-methoxy-phenyl) - ^ bu tv 1 / - ä thy 1 -am 1 η o / - S t han ο 1 -hy dr o ch lo ri d_ r ». > • -Λ, ·

Made from 41 -amino-3 1 -bromo-5 1 -cyan-2- ^ N- / 4- (4-methoxy-10 phenyl) -bu tyJL / -ethylamine £ / “acetophenone and sodium iborhydride in 90% igam methanol analog Example 1.

Melting point of the hydrochloride: 1 39-142 ° C.

'Example 111 1 "(4-Aino-3-bromo - 5-trifluoromethyl-phsnyl) -2 - / _ N- / 3- (4-methoxy-15 phenyl) -propyl / ~ msthy * lamino / ~ gth £ nol _________ fMade of 4 1 -amino-3 '-bromo-5 1 -trifluorinethyl-2- / N- / 3- (4-raethcxy-phenyl) -propyl / -methylamino / -acetophenone and sodium oorhydride in 90% methanol analogous to Example 1. oil.

IR spectrum (methylene chloride): NH2 3400 -f 3490 cm 1 20 OCH 2840 + 2940 cm “1 J -1 srom. C ~ C 1610 cm ÜV spectrum (xthanol): \ mrx. 223 r_m (0.26) 244 2H1 (0.1) /310 nm (very wide; 0.04) _ 81 _ '

Example 112 1 "(4- £ mir-o-3 ~ broi & -5-cyanophenyl) -2- £ î- (4 ** phsnyl-butyl) methyl airdrto / -HthanQl hydrochloride _ _ __________

Prepared from 4'-aaino-3 * -broia-51 -cyan-2- ^ ï- (4-phenyl-butyl) -5 iaethyleinino / -acetophenone and Xvafcriuyborhydrid in SOtigeai methanol analogously to Example 1

Hydrochloride peak: 153-155 ° C.

O 'V /

Example 113 1 - (4-lîaino-3-cyan-5-f fluorophenyl) -2- / K- / 2- (4 "'* ieetricxy-phanylî -1 or ethyl / ethylagdno / - ethanol -hvdroch.lorid

Prepared to 41 - && ino-3 V-cynn-51 -flror-2 - / ^ - / 2- {4-ïnsthc-xy- · phenyl) -ethyl / “inathyl £ jiiirso / -aeet-: phinon and Hatriirniorhyörid in SG % içeïa methanol analogous to Example 1.

Melting point of the hydrochloride: sintering from 66 ° C.

15 bar.: C 60.1 H 6.12 Cl 3.35 N 11.05 Found: 53.31 6.07 9.40 10.69; o; Example 114! j | 1- (4-Amino-3,5-dichlorophenyl) (3-phenylsulf enyl-propyl) - i '·' "methylamino / ethanol _ ___ ___________ _____: _____ 1.

20 Made from 4 * -Amiiio-2-brom-3 ’, 51 -cichler - & eetcphenon, Μι · / 3- (4-Methcxy-phenylsulfenyl) -propyl /“ ^ Bthylasin and Katrius-! borohydride in 80% methanol analogous to Example 2. oil.

; 13 spectrum (methylene chloride): 3390 + 3430 cm 1 ji OH 2600 * 36SO cm ”1 j 25 uV spectrum (ethanol) irax. 246 nm (0.15)! / -300 ma (0.05)

Example 115 - c2 .......- 1 - (4 -. & Aino-3,5-dichlorophenyl) (4-hydroxy-pbenyl) -pro-. pvl / -aminp / -âthanol _____________ _________________________

Manufactured from 4'-amino-3 1,5'-dichloro "2- / N - / 3" (4-hydroxy- '5 phenyl) -propyl / -eiiiino / -acetopharion and îîatriuriborhydrid in aqueous tetrahydrofuran analogously to example 3. oil.

_ IR spectrum (KBr): OH, NH, 3300 - 3600 cm ^} Δ -1 J aroma. C = C 1615 cm UV spectrum (ethanol + KOH) i! <Max. 244 nra (0.26) 10 239 nm (0.03)

Example 116 1- (4 “& aino“ 3,5-dichloro-phsnyl) -2- / ΙΪ- / 3 “(i-chlorophenyl) propyl /“ amino / -ethano1

Made from 41-amino-3 ', 5'-d.lchlor - 2- / N- / 3- (4-chloro-15 phenyl) -propyl / -amino / -acetophenone "and sodium borohydride in aqueous tetrahydrofuran analogous to example 3.

O

Melting point: 103-106 C.

Example 117 "1- (4-JLmino-3,5-dichloro-phsr * yl) (4 -htydrc: /. Y" phenyl) -1 -.. 20 ma thy1-propy1 / -is opr ooy 1 at irx oj - ä tha η ο 1 ___ __ _____

Made from 4 '-umino-3', 5'-c.iehler-2- / 11- / 3- {4-hydrcxy- 'phsnyl) “1“ i;' sthyl "propy] ^“ * iscprcpylirin't / ~ 'i - etrghenone and sodium trihydride analogous to Example 3. Oil.

3sr. : C 61.31 H 6.36 Cl 17.24 N 6.81 25 Found: 61, 07 6.85 16, -57 6.53 ..... - 33 -

Example 118 JL _ 1- (4-aminc-3,5-dichlorophenyl) -2- (β ~ / _2- (4-hydroxy-phenyl) * = * 1 -niefchyl-prosyl / ~ ethylcaninQ / -Sthc. nQl ______

Made from 4 * -Æasino-3f, 5 * -dichlor-2- / N- / 3- (4-hydroxy-5-plienyl) -1-methyl-propyl / -âthyl £ ïüiîig / * - aeôtophenone and liafcriusy-borohydride analog Example 3. Oil.

"Bear .: C 60.45 H 6.60 Cl 17.85 N 7.05

Found: 60.45 6.76 17.70 6.86 o

Example 119 101- {4-Methyl-1-ejsino-3,5-dichlorophanyl) -2- (11- / 2- (4-hydroxy-phsn 1 "rr.3thyl-nrcoyl / -rr.-3thyla5iinoy-ëtbanol

Made from 4 * -l'3ihy2n :: dno-3 1.51 "dich! Or-2- / N- / 3 ~ (4-hydr phenyl) -1-ethyl propyl / -n.sthyl srdnc / 'acetophenone and natrir * borohydride analogous to Example 3. oil.

15'3. : C 60.45 H 6.60 Cl 17.85 N 7.05 Found: 60.58 6.73 17.50 5.71 0

Example 120 1- (4-diethylamine-3,5-dicfclor ~ ph eny 1} -2 ~ / N- £ 3- (4-hydroxy- * "" phenyl) -1 -methyl-procy 1 / -it- e t hy 1 an-1 no / - ä th s η ο 1 _________ 20 Made from 4'-Din; ethylarBnc - 3 *, 5 '~ êiehlor-2 ~ / H- £ 3- (4-Lv droxy- phenyl) -1-methyl 1-propyl / -r.ethy 1 arrdno / tophencn and triur & bcrhydrid analogously to Example 3. Oil.

Bar.: C 61.31 H 6.36 Cl 17.24 N 6.31

Found: 61.28 6.57 16, SO 6.42 / i

Example 121-84-1 - (4-acetyl-iaino-3,5-dichlorophenyl) -2- / S- / 3- {4-hydroxy-phanyl) -1 -me thy 1-propv l / -me thy 1 am ί ώο7-ethanol _______________... "

Manufactured from 41 -acetylaraino-3 ', 5 * -dichloro-2- / N- / 3- (4-hydroxy-5 "phenyl) -1-methyl-propy37-methylamino / -aetophcnone and sodium borohydride analogously to Example 3 . Foam.

IS spectrum (methylene chloride): OH 35SO cm 1 NH. 3410 cm "1 N-alkyl 2800 cm 1 0 10 C = 0. 1700 cm "1 C = C 1610, 1595 cm" 1

Amide II 1515 cm “1 UV spectrum (ethanol) i \ max. 250 nm (0.3; shoulder) 280 nm (0.04) 15 (ethanol + KOH) O-max. 243 nm (Oj46), 294 nm (0.08) ’

Example 122 1- (4- £ thoxycarbonylaiaino-3,5-dichlorophenyl) -2- / pi- £ 3- (4-hydroxy-Q phsnyl) -1 -methyl-propyl / -iaethylamino / -anol 20 from 4'-ethoxycarbcnylamino-3 ', 5 "-dichloro-2- / N- / 3- (4-hydroxyphenyl) -1-methyl-propy £ 7 - &. ethyl £ irtiiiO / ~ ace tophenone and sodium borohydride analogously Example 3. Oil.

Bar .: C 58.02 H 6.20 Cl 15.57 N 6.15

Found: 58.20 6.32 15.32 6.03 l- ~ \ \

V

Ssigpial 123 - 85 -

Pacaraat A and B of 1- (4 “AmiRO-3-cyan“ 5-fluorophenyl) gsjdiyl- 3- (4-hydroxy-phsnyl) -propyl / -methyI a "5.nq / -gthanol_ _ j

Manufactured from 4'-amino-31-cyan-5 '-fluoro-2- ^ N- £ 1 -mathyl-3- (4-; "- 5 hydrosy-plienyl) -propyî7-methylamino / acetophenone and sodium borohydride Analogously to Example 3. The mixture of the diastereomar racemates obtained is separated by means of column chromatography (SiO 2; i ethylene chloride: methanol: concentrated ammonia = 50: 1: 0.1).

y! O Racemat Ai 10 melting point: 161-163 ° C.

13; C-1 HiR spectrum (dg-Dimefchylsulfcxid): Ï CH, i 3; - · -CH2-CH2-CH- 37.17 ppm i CH, l ^ -CH2 “CH2-CH- 57.91 ppm j .Λ ^ CH“ CH3 13.26 ppm (J —_ 15 ^ K-CH3 35 , 74 ppm ^ '^ 14-CH2- 60.90 ppm

OH

- CH - 69.21 ppm * / \ fi ^.

I *:> · j i | «- 36 - ........ '

Bscssiat B:

Solslpunkt: 92-98 ° C.

Spectrum (dg-dimethyl sulfoxide); CH_ J 3 -CH2-CH2-CH- 36.52 ppm CH-I 3 5 -CH - CH0-CK- 57.78 ppm, j 2 2 - ^ CH-CH3 13.19 ppm ^ K “CH3 35, 74 ppm x 61.48 ppm

OH

- CH - 69.02 ppm 10 Example 124 O __ 1 “(4-2mino- 3-cyaiï-5-fluoropheny 1) -2- ^ N- £ 1 -methyl-3- (4-methoxy-g- hssyl) -rr-ropyiy-cinlnp / -g thssol ___________________

Made from 41 "Axino-3'-cyan-5 * -fluoro-2- / N- / 1-n ethyl-3- {4-m3thoj: y-phenyl) -propyi7- £ mino /" aoetc-pherion '. : r> d l'atriunborhydri.ä α ciÎîS-LOçj âsxspxel 3.

S clirae 1z point: 103-110 ° C.

/ /: I y '---------------------------- --- 87—

Example 125 1- (4-Aminc-3-cyan-5-fluorophenyl) -2- / N- / J ~ nethyl-3- (4-hydre-xy-phanyl) -proDyl / -5itiino / -âi: hanol ........... _ __

Made from 4, -amino-3, -cyan-5, -fluoro-2- / N- / 1-mefchyl “-3 - (4-5 hydroKy-pheayl) ** propyi7-amino / -acetophenone and liatriuH ' ooriiydri d analogously to Example 3.

Melting point: 162-1 64 ° C.

O

Example 126 1- (4-lJsino-3-cyan-5-f luor-phsnyl) -2- £ ï ~ £ 1 -methyl-3- {4-msth.cxy-10 pbsnyl) -propyl / -msthylcirdnpy-§ thanol ____ I-Ierga made from 1- (4-Airiino-3-cyan-5-fluorophenyl) -2 - ^ - / 1- iüethyl-3- (4-hyroxy-phsnyl) -prcpy_l / "- ': 3thyla : i; ino / - “ethanol and dimethyl sulfate / 1 N sodium hydroxide in tetrahydrofuran analogous to Example 4. oil.

15 IR spectrum (methylene chloride): NH2 3400 + 3500 cm 1 0-CH3 2830 cm “1 N-alkyl 2800 cm 1 QC ~ N 2210 cm“ 1 C = C 1580, 1510 cm “1 20 C = C t deformation 1520 cm- 1 W spectrum (ethanol) / k ir.ax. ' 242 nm (0.27) 278 nm (0.05) / 236 nm (0.05) 324: rn (0.12)

Example 127 .....- 88 - “....." “" '.....' 1 “(4 ~ Äirdno-3f 5-âichlor-phenyl) -2 ™ ^ N" - (1- raeth.yl ~ 2 ~ ph '= noxy “äthyl} -cjrdnpV-äthanol-hydrochlQrid _____________ __________

Made from 4-Amino-3 *, S-dichloro-acetopfcanon, Selandioxid,.

5 1-methyl-2-phenoxy-ethylmin and sodium borohydride analogously to Example 5. Amorphous hydrochloride.

SI spectrum (methylene chloride); NH2 3390 + 34 30 cm ^ QV ^ Spsktrum (ethanol): ^ ioax. 245 nm (0.15) 300 ran (0.04)

[J

10 Example 128 1- (4-AKiina-3,5-dichlorophenyl) -2- / N- / 3- (4-fluoro-phenyl) -prcpyl / -aiîiin 3 / ~~ ß. t h an ο 1 ghydroch 1 o r i d. · _

Made from S-dichloroscetophenone, selenium dioxide, 3- (4-fluoro-phenyl) -propylaiain and Katriumborhydrid analogously to example 5.

Melting point of the hydrochloride; 1S5 - 187 ° C (dec.), No

Example 129 1- (4-Amino-3,5-dichlorophenyl) -2- / N- (3-phenyl-1-methylpropyl) ~ xnethylamino7- ethano 1 _____ _ __ _________ 20 Prepared from 4 'amines -3 ', 5 * -dichloro-'acetv-rhanc-n, selandicxide, 3-phenyl-1-methyl-propylamine and Katriusiborhydrid analogously to Example 5. 91.

IR-Spaktruai (methylene chloride): NH 33 30 4- 3490 cm "* · OH 3t00 4- 36c * 0 cm 25 UV spectrum (ethanol); isax. 245 nm (0.18) / 300 nm (0.06) ..... .......... ~ 89 - ........

Example 130 1- (4-Äiaino-3,5-dichloropheny1) -2- / N “(1 -B; ethyl“ 2 ~ phsncty “£ thyl) - 5iaing / - * ethanol ~ hydrochloride _______________________________! Made from 4- ^ 1110-3 ^ 5-dichloro-acstophsnoa, Sslendioxid, | 5 1-Msthyl-2-phenoxy-äthyläain and NatriürbOidiydrid analog at ™ S game 5.

I Melting point of the hydrochloride: 122-125 ° C.

i X

Example 131 N- / 3- (4-Amino “3-broin“ ph £ nyl) -propyl / “” · - / 2- {3,4-dimath crxy-phs-j 10 ayl) - 'ethyl / “n ; sfchyl £ iiiin ~ hydrochloride _____ ____________________

Made from N-Kethyl ~ N- / 2- (3,4-diHtathcxy ~ phenyl) -sthyl / -3-. * (i-c3iiiO ™ 3.5 "àibroïâ * 'pI * ç.a.ylî; -prcpicnaund X * ith.i * u5alusinlu- [- hydride in absolute tetrahydrofuran analogous to Example 7.

o n

Melting point of the hydrochloride: 70-120 C (sintering).

15 IR spectrum (KBr): NH ® 2500 - 2650 cm ^ i alkyl 2500 - 3000 cm 1 | U? Spectrum (Sthanol) s ^ inax. 234 nm (0.17) Q 2S0 nm (0.04) 300 nm (shoulder; 0.03) L - 20 Example 132 N "£ 2- (4" Aiüino-3-chlorophenyl) -2 ih / l / '- i; ~ (1 ethyl ^ S-phenyl-propy * \., isopropylamine ......................

Bergastellt from 4 ™ Araino-3, S-dichloro-N-isopropyl-N "(1 -mathyi-3-; phsnyl-propylj-phsnylessigsäureamid and LithiurmlurAiniurkyctrid 25 in tetrahydrofuran analogously to Example 7. Oil. Ί IR spectrum (methylene chloride): NH2 3390 + 3490 cm i 'üV-Spsptrum (ethanol): ^ rax. 241 nm (0.15)! 7 ... ___________ 300: -. T; (0.03) <- - 90 - .... . .......

Example 133 Λ N ™ / 2 “(4-Α $ ηίηο-3,5-dichlorophenyl) - * thyl / -N- (1-methyl-3-phenyl-propyl) -isopropylamine ^ ^ _____________ _____

Made from 4- £ mino-3,5-dichloro-N-isopropyl-N- (1-methyl-3-5 phenyl-propyl) -phenylacetic acid amide and lithium aluminum hydride in tetrahydrofuran analogously to Example 7. Oil.

XSr spectrum (methylene chloride): 3390 + 3490 cm ^ UV spectrum (ethanol) max. 245 nm (0.15) 302 nm (0.04) u 10 Example 134 Σ3- / 2- (4- £ mino-3,5-di chlorophenyl) ethyl / -3- (4-fluoro-phsnyl ) - propylc-min hydrochloride / ____

Prepared from 4- £ mino-3,5-dichlc> r-N- £ 3- (4-f incr-phenyl) -prc-pyl / -phenylacetic acid amide and lithium aluminum hydride in tetra-hydrofuran analogously to Example 7.

O

Ice chlorine point: 205-206 C.

0

Example 135 N- / 2- (4- £ mino-3,5-dichloro-pheny1) ethyl / -N- (1-methyl-3-pheny1-propyl) methyl amine 20 Made from 4-aeosino-3, 5-di chloro (1 -r.ahhyI-3-rh eryl-pxc-pyl) -phenylacetic acid amide and LitMuraiuminiurhydrid in tetrahydrofuran analogously to Example 7. Oil.

XR spectrum (methylene chloride): 3330 -f 3490 cm ^ uV spectrum (ethanol): r = x. 243 .n (0.14) 25. 300 im (0.05) / * * Z-sis pi al 136 (4-ijaiao-3,5-dichlorophenyl) ethyl / -N- / 3- (4-methcxy-phsnyr-snlfenyl) - prôpyl / -aathylgain ...... _ _ _ _______

Prepared from 4-amino-3,5-âichlGr-N- / 3- (4-msthcxy-phenylsul-5 fsnyl) -propyl / -N-îns-fchyl ~ pheiiyle.esigs «ureajri.ld and Lithiamalisninix '^ - hydride in tetrahydrofuran analogously to Example 7. oil.

XRr spectrum (Kathylenchlcrid): NH2 3390 -f 3490 cm ^ ÖV-Spekfcrum (ethanol): max. 245 nra (0.16) 300 ran (0.04). 0 10 Example _1_3_7 N- / 2- {4-Amino-3-bromo-pb.enyl) -o thyl / -N- £ 4- (4-methoxy-phenyl) -buty1 / -mathy1 amine __ _______________

Manufactured from 4-smino- “3“ h ^ o: a * !: 7 “/ 2“ (4-methexy-phsnyl) -hutyl / -K-msthyl-phsnylacetic acid amide and lithium aluminum halide hycrid in 15 absolute tetrahydrofuran analogous to example 8.

IE * spectrum (Kathvlenchlorid): NH- 3380 t 3470 cm ^ 2 -1 OCH ^ 2330 + 2330 cm ify aroia. C = C 1620 cm ** I-34R spectrum (CDCl3 / D20): aromatic H 6.4-7.3 ppa (m, 7H) 20 0CH3 3.7 ppm (s, 3H) NCH3 2.2 ppm (s, 3H) aliph. H 1.3-2.3 ppm (m, 8H)

Example 138 IÏ- / 2- (4-Ämino-3-bromophenyl) -athyl / -N- £ 2- {4 ~ msthcxy-phsry1) -25 Sthy 1./-Π3t ay 1 am 1 η _ ________

Made from 4-amino-3-bromo-N- £ 2- (4-methoxy-pheny1) -ethyl / -. <·

X

....... ^ ~ Ç2 ~ - .............

N-methyl-phenylacetic acid amide and lithittmalirainium hydride in absolute tetrahydrofuran as in Example 8.

IR spectrum (methylene chloride): 3380 + 3480 cm ~ 1 OCH, 2340 + 2340 cm "1 5 aroma. C - C 1620 cm h UV spectrum (ethanol);% max. 224 ra (0.24) 242 nm (0.15) 280 nm (wide; 0.03) - 300 nm (wide; 0.03)

J

10 Example 139 ÎÎ- / 2- (4-lmino-3-fluorophanyl) ethyl / ~ N - / 3- (4-msthoxy-pheny 1) - propy l / -re thv 1 am ln _____________ ____________ _ _ __ __ _________

Made from 4-.Amine-3-fluorine-N- / 3- (4-methoxy-phenyl) -propyl / - K-methyl-phenylessicsgureamide and lithium aluminum hydride. in '= * 15 absolute tetrahydrofuran analogous to Example 8. oil.

IR spectrum (methylene chloride): 3390 + 3460 cm 1 OCH 2840 + 2340 cm “1 J -1 arem. C-C 1510 cm OV spectrum (ethanol): * X max. 227 nm (0.3) 0 20 279 nm (0.06) 285 nm (0.06)%

Example 140 N- / 2- (4-ÄrairiO-3-chlorophe: .yl) -ethy3 ./- 17 · \ £ 3- (4 -: -. = Thexy-phsny1} - 'propyl / -methyl £ i? .in _ _.

25 Made from 4-Airdr.o-3- * ehXc-r-ethyl-lî- £ 3- (4-msthoxy-pheny 1) -propyl / ”phe: iylessigs £ urcardd rr; d LithivmaliuHiniirthydrid in absolute tetrahydrofuran analogously to Example 8 Resin.

/ -χ XR = Spek.fcrujn (l-ethylene chloride): KH2 3350 -t 3470 cm 1 OCH 2340 4- 2940 cm “1 arcm. C - C 1510 cm W ~ Sp = khrua (ethanol): Ον ^ ax. 224 ma (0.25) 5 240 nm (0.13) 230 nm (0.04) 300 ma (0.03)

Example 141 / * "·> U .. _ _ Iî -, / 3" {4-Amino "-3, S-dichlorophenyl)“ propyl / -N- ^ 3- (4-methoKy-phe-10 ^ l) j ^ pgqoyiyp ^: ln ~ hydrqchlorld _

Made from 3- (4-.Smiir.iO-3,5-dichlorophenyl) - K- / 3- (4-ir.ethoxy-. - phsnyl) -prc * pyl / -propior.S £ ursamide and Lithium aluminum hydride in absolute tetrahydrofuran analogous to Example 8.%

Melting point of the hydrochloride: 138 ~ 142 ° C.

15 Example 142 I5- £ 3- (4- £ jnino-3,5-dichloro-phsnyl) propyl / -N- / 2- (4-methoxy-O phenyl) ethyl / methylamine ~ dihydrochloride

Herges divides from 3- (4- £ m ± nG-3 f 5 "dichlar ~ phanyl) -N-methyl-N- £ 2- (4-msthcxy-phenyl)" ethyl / propic acid arid and lithium aluminum 20 hydride in absolute tetrahydrofuran analogous to Example 8. Melting point of Dihy drc-ch 1 ori.ds: 147-157 ° C.

L · '...... ......... ........ - S4 ->

Example 143 N- ^ 2- (4-Amino-3,5-dichlorophenyl) -Mfciiyl / "N- ^ 4- (4-msthosy-phs-ny 1) - butyl? -Cônin-hy drochlor id 4

Prepared using N- ^ 2- (4-amino-3,5-dichloro-phsnyl) -ethy] / “^ - * (4-5 methoxy-phenyl) -butyric acid acid and lithium aluminum hydride in absolute tetrahydrofuran analogously to Example 8.

_The melting point of the hydrochloride: 186-189 ° C.

~ J Example 144 (4-AHiino * -3,5-dichlorophenyl) -athyl / -N ~ £ 3- (4-chlorophenyl) - "50 pgppyl / pgmin-hyd ^ -chloride ______________________________________

Eergs made from 4- ~ aminc-3,5-dichloro-N- / 3- (4-chlorophen.yl) -pro-Kri / "rph'snylacetic acid amide and Lithiuînaluminirri’ydriâ in absolute tetrahydrofuran analogously to Example 8.

Step 1 point of hydrochloride: 186-190 ° C.

15 Bsispdsl 145 o N “Z ^ 2- (4“ 2UainO “3,5-dichlorophenyl) -ät hy 1 / -N- / J- (4-methoxy-phenyl) - ~ j soorop '/ 1 amln _ _.

HergQstelit from N- / 2- (4-amino-3,5-dichlorophenyl) -âthyl / “N-iso-propy) _4_ (4-methcxy-phenyi) -buttersuramide and lithium aluminum“ “* ^ * d rn £ jdso .'- U'c. & Ji TeUrahvdrofuran analogously to Example 8oil. iÄS “S ^ sktrum (cathylene chloride): NH2 3390 + 3490 cm” 1 0CHo 2850 + 2930 cm "1 3 -1 aroma. C ~ C 1610 cm w *" s £ sktrum {ethanol) î% r-ax. 242 un (0.12) * / 230 nm (shoulder; 0.04) 301 nm (0.04) ”” ............... "- 95: - *

Example 146 N- / 2 - {4 ”At5ino-3 r 5-dichlorophanyl) -thyl / -N- / 2- (4 = -?;. = Tbory-phsnyl) -är.hy 1 / -1 s ooropy 1 am in ______ _ _ ______

Prepared from N- £ 2- (4-Ämino-3,5-dichXor-phs2iyl) -äthyl / -N-iso-5 propyl-4-msthoxy-piisnyless.igslureamid and Lithiumslusiuiu? Nhydrid in absolute tetrahydrofuran analogously to Example 3. Oil .

-1 -I-R spectrum (methylene chloride): 3390 + 3430 ca OCH, 2830 + 2360 cm "1 S -1 aromatic C - C 1610 cm 0 10 UV spectrum (ethanol):" X sax. 244 nm (shoulder; 0.12) 280 nm (shoulder; 0.05) 301 nm (0.05). Example 147! -. 'i - N- ^ 2- (4-Amino-3,5-dichlorophenyl) ethyl / -ir- £ 2- (4 ~ -vathoxy * -phe- | 15 nyD ethyl / amine hydrochloride! Manufactured by sus 4-JLm.in.c-3,5-dichlor ~ N- / 2 ~ (4-nethcxy-phsnyl) - ethyl / “phanyiessigseureaüiid and lithium aluminum hydride in abso- / Λ lute tetrahydrofuran analogously to Example 8.

’S> o

Melting point of the hydrochloride: 205-208 C.

, 20 Example 148 t - ^ [* N- £ 3- (4 - Jaino-3,5-dibromo-pheny 1) -prc-gyl / "-“ ^ “(3,« - diaisthoxy-phsr.yl) -ethyl / -methylajnln ________________

Made from N-Ksthyl-K- ^ 2- (3,4-öimetho; -: y ~ phsnyl) -ëthylj- | 3- (4 ”aHi ~ c-3f5-dibros-phenyl) -propionic acid anide and Lithiumlu- 25sinimnhydrid in absolute tetrahydrofuran analogously to Example 8. oil.

! / ^ ji _ __ ________ ______ ___ _ _ ..... _......... _ ......

♦.

- - ΙΕ spectrum (aesthetic chloride): NH2 34ôO + 3380 cm 1 OCH3 2840 + 2940 cm ”1 EMR-3 spectrum (CDCl3 / D20): 0-CH3 4.85 ppm (s, SH) N-CH3 2.25 puni (sr3H) 5 arorn.H 6.75 ppm (d, 3H) 7.2 ppm (s, 2H) aliph.H 1.5-2.9 ppm (m, 12H)

Balsplel 149 O N- / 2- (4-amines.3,5,5-dichlorophenyl) -athyl / -3-phsnyl-propylamine-10 hydrochloride

Kergs made from 4-amine-3,5-dichloro-S- (3-phsnyi-propy1) -phsnyl-acetic acid and lithium aluminum hydride in tetrahydrofuran analogously to Example 8.

• Melting point of the hydrochloride: 197-199 ° C.

15 Example 150 N- £ 2- (4- & ainc-3-bromo-5-cyanophenyl) ethyl / -N- £ 4- (4-siethoxy-r y pbenyl) butyl / benzylamine

Manufactured from 1-ethoxy car bcnylc-xy-1- (4-amino-2-bromo-5 ™ cyan-pbenyl) -2- / E- / 4- (4-methcxy-pbsnyl) -buty3 / -bsiizylamino / - «Than 20 and, natriuraborhyörid in isopropanol analogous to Example 9. oil.

IR spectrum (methylene chloride): NH, 3390 + 3490 cm 1 1 .., - 1 OCH, 2crO t 2930 cm - * -1 CN 2210 cm aroma. C = C 1620 cm 1 25 ÜV spectrum (ethanol): ^ ri-ax. 222 nm (0.42) / 244 nm (shoulder; 0.09) 335 nm (broad; 0.05) ......... -97 -..... .....

Example 151 N- / 2- (4 ~ £ mino- 3 ™ bromo-5-cy £ n-phenyl) -ethyj / -Ν-- £ 4- (4-mathoxy ~ phs · -nyl) --bi ^ tyl / pallylaiain __

Made from 1-ethoxycarbonyloxy-1- (4-amino-3 "broni-5-cyan-5 phsn] fl)" 2- ^ N - ^ _ 4- (4-issthoxy-phenyl) -butyl / -allylamino / -ethane and natrimoborohydride in isopropanol analogous to Example 9. oil. XHr-Spsktruin (methylene chloride): NH2 3350 -'r 3450 cm 1 0CH3 2830 + 2930 cm “1 CN 2210 cm" 1 0 10 a rem. C = C 1620 cm 1 ÜV spectra (ethanol): θ '* rvax. 222 nm (0.49) 244 nm (shoulder; 0.1) 335 im (broad; 0, C5)

Example 152 15 N- £ 2- (4-Amino-3-broiTi-5 ~ cyan ~ phenyl) -ethy 1 / -N ~~ / 4- \ “3. memo ^ y-pn ^ "* nyl) -buty! l / - * sthylamine

Made from 1-ethoxycarbonylcxy-1- (4 ~ omo-3-bromo-5-cyan-Q phenyl) -2- / N - / 4 "(4-methoxy-pfcenyl) -buty £ 7-ethyl £ irdno / -ethane and

Sodium borohydride in isopropanol analogous to Example 9. Oil.

20 is-spsktrum (l'ethylene chloride); lîH «3350 + 3490 cm 1 z -1 0CH3 2330 + 2960 cm CN 2210 cm" 1 r - 1 arem. C ~ C 1620 cm UV spectrum (ethanol): nax. 222 am (0.49) 25 244 nm ( Shoulder; 0, C3) '_ 333 nm (broad; 0.06) ......... ..... s 3 _

Example 153 ♦ K— / 2- (4-Äiaino- 3-brom- 5-cya.a-pb eay 1) kyi7 “^ '“ τί. ** “^ 4-iaethoxy-phô— nyl) -bûfcvÜ-isopropvlaiain ...................,. _. .__

Made from 1-Ätlioxycarbonyloxy-1- (4 ~ cJäino-3-brGm-5 "cyan" 5 phenyl) -2- / N- / 4- (4-msthcxy ~ phenyl) -butyl ^ isopropylarain ^ stlian and sodium borohydride in isopropanol as in Example 9. Resin. -IR- "spectrum (methyl chloride): NH2 3390 + 3490 cm 1 0CH3 2S30 + 2560 cm" 1 CN 2210 cm "1

'' S

O -jo aroma C = C 1620 cm “1 OV spectrum (ethanol): max. 221 nm (0.53) 244 nm (shoulder? 0.1) 330 «nt (broad; 0.07)

Example 154 * 15 K- ^ 2- (4-Amino-3-bromo-5-cyanopheny1) ethyl / -N- £ 4- (4-netfcoxy-phe-ny 1) -bu ty 1 / -η -oropy 1 am in. _________ __

Made from 1- £ thGxycarbonylcxy-1-- (4-aiaino - 3-brciri-5-cyanophenyl) -2- / N - / _ 4- {4-methcxy-phanyl) -butyl / -n-propylamiiio / -ethane and sodium borohydride in isopropanol analogous to Example 9. oil.

20 IS "spectrum (methylene chloride): ÏÎH ^ · 3390 -f 3490 cm 1 CN 2210 cm" 1 OCH- 2830 -Î- 2950 cm "1 3 -1 aroma. C = C 1620 cm 1: * _ UV spectrum ( Ethanol): \;:. Ax. 222 (0.45) -. 25 244 nm (shoulder? 0, G3) 330 nir: (broad; 0.05)

Example 155

A

- ~ 99 ~ - ~ N- ^ 2- (4- £ mino-3-brQm-5-cyanophenyl) -athyl / -lî- (4-phenyl-butyl) - stethylainln __ __ __ __ _ __ ___

Prepared from 1 ~ ethosyearbonyloxy ~ 1- (4-amino-3-broni-5-cyan-5 phenyl) -2 - ^ - (4-phsnyl-butyl) -iüathylamino7-ethane and Katrima-borohydride in isopropanol as in Example 9. Oil.

Nuclear Magnetic Resonance Spectrum (CDC13); aroma H 1.0-7.4 ppm (m, 7H) NCH ^ 2.2 ppm (s, 3H) alioh. H 1.2-2.1 r.pm (m, 12H) o 1ö Example 156 K- / 2- (4 - &> nino-3 ~ cyan-5-fluoro "pbanyl) -ethyl /" K- £ 2- (4 ~ me ± hoxy-ph-snyl) -athy ^ -ffiethylsigin ___ _________ • ·

Manufactured from I-Xthcxycarbonylcxy-I- (4 ~ "mino-3-cyan-5-fluorophenyl) (4-msthoxy-phsnyl)" äthy £ 7 "sethylöiäino7" * äthan 15 and Katriræîborhydrid in isopropanol analogously to Example 9, oil . KKR spectrum (CDCl ^ / CH ^ OD): aroma H 6.7-7.2 ppm (hi, 6H) OCH2 3.75 ppm (s, 3H) Q NCH3 2.3 ppm (s, 3H) aliph . H 2.4-2.7 ppm (m, 8H) - 20 Example 157 N- £ 2- (4 «-umino-3-cyan-S-fluorophenyl) ethyl / '1ϊ ~ £ 3 ~ {4 -m3thcxy-. - phenyl) propyl / laethylamine hydrochloride _________ ’

Made from 1 -> Ithoxycarbonyloxy-1 - {4 ~ cm ± riO-3-cyan-5-fluor-phsnyl) -2 - / ^ - / 3- {ir ^ strcxy-pheny!) -Yrc pyl / -me thylamino / -M than ^ 5 and sodium borohydride in isopropanol analogous to Example 9. Hydrochloride as resin.

Λ -t - 100 - KMR spectrum (CDCl ^): aroma H 6.1-1.2 ppm (a, 6H) OCH ^ 3.75 ppm (s; 3H) ® NCH3 2.8 ppm (s; 3H) aliph. H 1.5-3.5 ppm (m; 10H) \ 5 Example 158 N- / 2- (4- £ mino-3-cyan-5-fluoro-phsnyl) -athyl / -N- £ 4- (4th -mathoxy-phe-nyl) "bntyl / -iaethylairtin

Manufactured from 1-ethoxycarbonyloxy-1- (4-amino-3-cyan-5-fluorophenyl) -2- / N- £ 4- (4-methoxy ~ phenyl) -b> ityl / -methylamino / - âthan 10 and Katri uîûborhydrid in isopropanol analogous to Example 9. Resin. ! 34E ~ Spectrum (CDCl ^ / ^ O) s aroma. H 7.2 ppm (s; 211) 6.35 ppm (q; 4H) OCH ^ 3.8 ppm (s; 3H) PCH ^ '2.25 'ppm (s; 3H) 15 aliphatic. H 1.5-2.7 ppm (m? 1211}

Example a1159 f "~ \ N- / 2- (4" amino-3-chloro-5 "trifl'aomiethyl-phenyl) -ethyl / -N- £ 4- (4-methoxy-phsnyl) -butyi / -msthyiaip. in ________

Made from 1 -Sthoxycarhonyloxy-1 - (4 ~ 5mino-3-chloro-5-tri- 20 _ - _ rluormethyl-phenyl) -2- / N- / 4- (4-methoxy-phenyl) ~ hutyl / -aethyl - Amino / -athan and Kati'iumborhydrid in Isvoro'na.nol analogously to Example 9.

Melting point: 29 ° C

Jf

Example ISO

..... .......... .....

. "dno“ 3 ** chlör * “5-triflpor3isthyl“ -ph. * nyl} -Sfchyl / -11- / 2- (4- mafchcsy-gheny1) »äthyiy-methylamine _ ___ __________

Made from 1-ethoxycarbonate lexy -1 ~ (4-amino-3-chloro-5 - tri-5 fiuosiBSthyl-phenyl) ~ 2- / JX- [2- (4-ir.e thcxy-pheny 1) - ethyl / -methyl-ssdno / -athan and natriurabor hydride in isopropanol analogous to example 9. Resin.

Ilv-Spsktriun (methylene chloride): KH0 · 3400 + 3500 cm ^ 1 “1 OCH, 2840 + 2960 cm- f. i ^ - 1 10 arcm. C = C 1610 cm UV spectrum (ethanol): \ sisx. 228 nra (shoulder; 0.10) 244 nm (0.10) 310 na (0.03) «* 'Example 161 15 11- / 2- (4“ Äiaino-3,5-dichlorophenyl) ethyl / -E- / 3- (4-f luor-phenyl} -propyl / · -methylamine ____

Eergs made from 1 "ethonycarbonylcxy-I- (4-cirdno-3,5-dichlcr-phe-Çj nyl) -2- / N- / 3- (4-fluorophenyl) -propyl / -methylamino / -ethane and

Sodium borohydride in isopropanol analogous to Example 9. oil.

20 IR spectrum (Kethylench'orid): 3390 4 * 3490 cm ^ UV spectrum (ethanol): max. 243 na (0.13) 300 nm (0.03)

Example 162 1 “(4-Äzrdna-3-trifluoraethyl-phenyl) -2- / î?“ £ 3- (4-methoxy-phenyl) - 25 ^ X-p: ipvlÿ “? RethYlamino /“ âthanol_ _____ _

Made from 1 - (4-amiric-3-bromo “5-trifluoromethyl-phenyl) -2- / 11- / 2- {i-rethcxy -'- phanyl)" pr-? Pyl / '* rethy3a: nin-o / "Itha :: - ol and Nasser .....

- 1C2 fabric in palladium ur.cxid on Bariunsulfat in Meihscel analogous to Example 11. Oil.

Ki-S spectrum (CDC13 / D20) î aro ~. H 5.6-7.3 ppm (sa; 7H) -CH-CH 4.5 ppm (t; 1H) 5. OCH3 3.7 ppm (s; 3H): NCR, 2.3 ppm (s; 3H) ); aliph. H 2.2-2.7 ppm (ra; 6H) -CH 1.8 ppm (g; 2H) E-ais ^ -iel 163 (jy 10 N- / 3- (4-7: estaitinee-3 , S-dichloro-phsnyl. -Propjrl / -N- / 2- (3,4-dimethoxy-phenyl) -ethyl / -methyl.? Jnin _____ ____________ ___

Hsagestalli ans $ 1- / 3- (4-amino-2,5-dicklor-phsnyl) -prop ^ l / -N- / 2- (3/4 “O.Aiti1'3tiioxy” piiaîi yl) -ethyl / -r . = thyl = rdn, acetyl chloride and triethylamine in toluene analogous to example "2. Oil.

15 lE ”spectrum (methylene chloride): MH 3405 cm 1- -1 OCH, 2S30 + 2940 cm * -1 CO 1700 cm ÜV spectrum (ethanol): \ man. 22: nm (shoulder; 0.17) 2EZ nm (0.04) 0 20 Example 164 1- (4- £ ia ± no-3,5-dichlorophenyl) -2- £ N-_3- (4- hydroxy-pheny 1) -1 -msthyl-propyl ^ -allylaininoy-äthanpl ____ __________ ___________

Made from 1- (4 ~ Ä2kino-:, 5-dichloro-phsnyl) -2- ^ 1- / 3- (4-hydroxy-pheny1) -1-methyl-propvl / -amir.o / -ethanol with allyl bromide / ^ Sodium carbonate in absolute ethanol analogous to Be ispis 1 13. Oil. IF. Spectrum (methyl chloride): OH 3580 cm 1 MH * 3390 + 3480 cm 1 / * £ * aliph. CH "1850 + 2930 cm" 1 C = C 1615 cm "1 ♦ ............. - ^ 03- ~~ .......

üV * = Spsktmm (ethanol): ^ isax. 243 nm (0.26) 282 nm (0.08) 300 nm (0.08) (ethanol + KOH): max. 242 nm (0.47) 5; 298 nm (0.19)

Example 165: 1- (4-imino-3,5-di'chlorophenyl) -2- / N- / 3- (4-hydroxy-phenyl) -pro-oy 1 / -i soprocylamina / —Ktha.no 1 — hy droch lorid _ _ _ 0 Γ "'*“ ....... ”" "~ _

Prepared 1- (4 — amino-3,5-dichlorophenyl) -2- / E- / 3 “(4-10 banzyloxy-phsnyl) propyl / isopropyl amide / ethanol and hydrogen in the presence of palladium on carbon analogous to Example 16. Melting point of the hydrochloride: 90-110 ° C.

Example 166 1 - (4 ".lmino-3-chlorophenyl) -2- / N- / J- (4-hydroxyphenyl) propylj- 15 ethylamine / ethanol .......... .......

Made from 1- (4-aminc-3,5-Öiehlor-phenyl) -2- / N- / 3 * · (4-benzyl-oxy-pheny 1) propyl / ethyl. = Mino7-ethanol and hydrogen in Presence of palladium on carbon analogous to Example 16. Resin.

IR spectrum (methylene chloride): 0H 3595 cm 20 NH2 3400 + 3490 cm “1 aliphatic. CH 2840 -5- 2940 cm “1 '- 2 -1 C - C diä cm UV spectrum (ethanol): ^ max. 227 nm (0.19) 244 nm (0.17) 25. 290 nm (0.04) (ethanol + KGH): * \ rax. 243 nm (0.32) 297 nm (0.08) / ♦: - 104 - * ~

Example 167 1 "(4-Amino-3,5-dichlorophenyl) -2- ^ N- £ 3- (4-hydroxy * -pher * yl) -prcpyl / -gthylaiainoy-ethanol_." ..,. .. -

Made from 1- (4-amino-3,5-dichlorophenyl) -2- ^ N- / 3- (4-ben; syl-5 cxy “phenyl) -propyl7 ~ ethylamino / ethanol and hydrogen in the presence of Palladium on carbon analogous to Example 16. Resin.

TH ^ spectrum (methylene chloride): OH 3590, 3620 + 3680 cm NH. 3390 + 3480 cm 1 2 -1 aroma. C = C 16 * 55 cm ^ 10 UV spectrum (ethanol): Λ max. 244 nm (0.17): 284 nm (0.06) 200 nm (0.05) (ethanol + Κ0Η): ^ max. 243 nm (0.31) 238 nm (0.08) 15 Example 168 K- / 3- (4-bimethylamino-3,5-dichlorophenyl) propyl / -N -, / 3- (4-ethoxy- ohenvl) -srooviy-methylamine .......

Q Made from N- / 3- (4-amino-3,5-dichlorophenyl) propyl / -N- £ 3- (4 “irtethoxy-phenyl) propyl / -ainin, paraformaldehyde and natrrum-20 cvanbcrhvdrid in Ethanol analogous to Example 101. Oil.

^ "-1 ÏR spectrum (ethylene chloride): 0CH3 2830 + 2S40 cm" NCH3 2790 cm-1 • NH-. 2nd -1 arcm. OC Vi \ o cm 25 KMR spectrum (CDC13 / D20): aromatic H 7.0 ppm (q; 4H) 7.1 ppm (s; 2H) 0CH3 3.75 ppm (s; 3H) N (CH3) 2 2.85 ppm (s; 63) aliphatic. H. 2.2-2.8 ppm (m; SH) 30 n-CH3 2/2 ppm ^ s; ff ^ -CH2- 1.6-1.8 ppm (q; 4H) J.1 game 169 "- 105 - 'îï- / 3- (4- & aino-3,5-dichlorophenyl) propyl / -N - / 3- (i-methoxy-pka- 'iiyl) ~ propyl / "iasthylainin | Made from N- / T- (4-amino-3,5-dichlorophenyl) propyl /" N "/ 3-5 (4-niethcxy-phenyl) propyl / amine, paraforma idehyde and sodium cyanoborohydride in ethanol as in Example 101. Oil.

"Ht spectrum (methylene chloride): 3390 + 3490 cm ^ ^“ 1 OCH-, 2830 4- 2940 cm 3 -1 _ aroiii. C = C 1610 cm LJ 10 ÖV spectrum (ethanol): max. 230 nm (shoulder ; 0.21) 242 nm (0f1) 278 + 285 nm (bre.it; 0.03) 302 nia (broad; 0.03). ~ Example 17Ό - 15.N- / 2- (4-Diinethylairdno-3 , 5-dichlorophenyl) -thyl / -K- / 3- (4-chlorophenyl) propyl / methylamine ___________ ___ _________________________

Made from N- / 2- (4-amino-3,5-dichlorophenyl) -athyl / ~ IS -_ / _ 3-O (4-chlorophenyl) propyl / amine, faraformaldehyde and sodium cyanoborohydride in ethanol analogous to Example 101. oil.

20 IR spectrum (methylene chloride): NCH ^ 2790 cm ^! <H2

NH

UV spectrum (ethanol): max. 273 nm (broad; 0.04) / \ ..... - 106 -

-S

}

Example 171 17- / 2- (4-.Smino-3,5-dichlorophenyl1) ethyl / -N- £ 3- (4-ehlor-phan yl) -propyi7 ~ 2-phenylethylajnin ~ hydrochloride _ · ' from N - ^ - (4-amino-3,5-dichlorophenyl) -athyjy-N- / 3-5 (4-chlorophenyl) propyî7-aïïin, phenylacetaldehyde and sodium cyanoborohydride in ethanol analogously to Example 101.

/ Melting point of the hydrochloride: 158-161 ° C.

t

Example 172 lik- (2- (4- £ mino-3,5-dichlorophenyl) ethyl / -N- £ 4- (4-mathosy-phe-10 ayl) -butyl7 “-athvlamin ____________________.___ '. Made from N- / 2- (4-amino-3, S-dichloroph-yl) ~ ethyl / -N- / 4- (4-meuhaxy-pheny 1) -butyl / '- amine, acetaldehyde and sodium cyanide barhvdrid in ethanol analogous to Example 101. Oil.

IH spectrum (methylene chloride): OCH ^ 2360 + 2930 cm 15 aroma. C = C 1610 cm W = Sr? Ktrum (ethanol): nax. 245 nm (0.09) 273 nm (0/02) pl 282 nm (0/02) 300 nm (0/01) - 20 Example 173 = N- £ 2- '4-2 · irdno “3.5- dichlor-pheny 1} -ë thyl / -H "Z?“ ^ xur-pnen / x) - propv \ J-ben zy 1 amine-hydro oh lor id ~

Bergt 'represents N ~ ^ 2- (4-amine-3, ö-dichlor-p * 1®1 * ·?' 1) (4-chloro-phsny1) -propyl / «amine, Senzaldshyd 'J ~ d Ä --tr3. · .ar ^ oi -25 hydride in ethanol analogous to Example 101.

Melting point of the hydrochloride: 164-168 ° C

/ /,: · "N

♦

Example 174 107-1 N- / 2- (4 ~ Ämino “3,5-dichlor-ph5ny 1) -Sthy (4-ehlor-phany1) - 'prcpyl7-isopropylamine _______ _ - -„ ^ __

Made from N- / 2- (4-A.mino-3,5-dichlorophenyl) “äthy1V-N” - / _ 3 "5. (4-chlorophenyl) propy £?“ Emine, acetone and Katriuseyanborohydride in absolute methanol analogous to Example 101. oil.

JLEr spectrum (methylene chloride): NH ~ 3390 + 3480 cm 1 ^ -1 aroma. C “C 1615 cm UV spectrum (ethanol): maxr 241 nm (0.13) 0 10 I 300 nm (0.05)

Example 175 N ~ ZJ -methyl-2- (4-amino-3,5-dichloro-phexiyl) ethyl / -N- / 3- (4-meth- "· * 'oxyphsnyl) -pgopyl7-5min-hydrochloric acid id _ .......__ ·

Prepared from 1- (4'-amino-B '»S'-dichlorophenyl) acetone, 3- {4-15 methoxyphenyl) propylaiain and sodium cyanoborohydride in ethanol analogously to Example 101.

Melting point of the hydrochloride: 193-1S5 ° C.

0

Example 176 N- £ 2- (4-Amino-3,5-dichlorophenyl) ethyl / -N- £ 3- (4-chlorophenyl) -20 propyl / -n-propylamine __ __ _ _ ___ _ _____ ___

Made from N- / 2- (4-Amnü-3,5 - * '5ichlorophenyl} ~ äthyV-N- £ 3- (4-chlorophenyl) propyl / - £ iain, propionaldehyde and sodium cyanoborohydride in Ethanol analogous to example 101. oil.

-r JR spectrum iMethvlenchlc-r 5 d): ilH "3330 -5- 34 * 30 cm * * y 25 aroma. C ^ C 1610 cm" 1 UV spectrum (ethanol): rr.ax. 242 nm (0 , 13) / 301 nm (0.05)

Example 177-108 - N- / 2- (4-amino-3,5-dichlorophenyl) ethyl / -N- £ 3- (4-chlorophenyl) propyï7-athylainine ______________.

Made from N - ^ - (4-amino-3,5-dichlorophenyl) ethyl / -N- / 3-5 (4-chlorophenyl) propyl _ / - amine, acetaldehyde and sodium cyanoborohydride in ethanol pH 6 - 6.5 analogous to Example 101. oil.

- XR = spectrum (methylene chloride): NH_ 3390 + 3480 cm 1 Δ -1 aroma. C = C 1615 cm f-y UV spectrum (ethanol): max. 242 nm (0.14) ~ 10 305 nm (0.04)

Example 178 N- £ 2- (4-amino-3,5-dichlorophenyl) -styl / -K- ^ 2- (4-m £ thoxy-phs-nyl) -ethyl / -athylamlin__ ________ __ __

Made from N- / 2- (4-ajnino-3,5-dichlorophenyl) ”ethyl / - N- / 2-15 (4-methoxy-phanyl) ethyl / amine, acetaldehyde and sodium cyanoborohydride in ethanol analogously Example 101. Oil.

IR spectrum (methylene chloride): 3390 t 34SO cm 1 O ä OCH. 2830 + 2940.cm ”1 0 -1 aroma. C = C 1620 cm 20 uv spectrum (ethanol): max. 244 nm (0.16) 284 nm (shoulder, 0.04) ~ - 300 nm (0.04)

Example 179 N- £ T-methyl-2- (4-emino-3,5-dichlorophenyl) -'4thy 1 / -N- / 3- (4 - "- athcxy -25 phenyl) -pyopyl / -methylamine _

Made from 1- (41-amine-31,5'-dichloro-ohanyl) acetone, 3— (4 - //.

i • τ '- 103 -

V

Kethoxyphenyl) -N-meth yl-propylamine and sodium cyanoborohydride. In anol as in Example 101. Oil.

IR spectrum (methylene chloride): 3390 -4 * 34SO cm'1 OCH- 2340 * 2S40 cm “1 J“ 1 5 arem. C-C 1615 cm UV = “spectrum (ethanol): max: 242 nm (0r 14) 230 nm (shoulder; 0.04) 302 nm (0.05)

Example ISO

r \ --------

K.J

10 N- / 2 "(4-amine-3,5-dichlorophenyl) ethyl / -N- (3-phenylpropyl) isopropylamine hygrochloride mm.

Made from N- / 2- (4 "A.; rdno-3,5-dichlorophenyl) ethyl 1 / -3-phenyl-propylamine, acetone, molecular sieve 3X and sodium cyanoborohydride in absolute methanol analogous to Example 101. Scharm.

15 IR current (methylene chloride): NH- 3390 + 3430 cm “1 2r \ * NH ^ 2300 - 2400 cm“ 1 UV spectrum (ethanol): max. 245 nm (0.12) 302 nm (0.04) o

Example 181 20 1- (4-Amino-3,5-dichlorophenyl) -2- ^ R- (1 -mefchy1-3-ph eny1-propy1) - methyle.mino / ethanol hydrochloride ___ ____ - Made from 1 - (4-Amino-3,5-cLi; lilor-ph rvy.l Î * - 2- / N- (1 -methyl- 3-phsny1-propy1) -amino / ethanol, paraformaldehyde and catrium cyanoborohydride in Ethanol analogous to Example 101. Oily hydrochloride.

25 IR spectra (methylene chloride): NH- 3390 + 3490 cm 1 • -Ό.-Î NH 2300-2400 cm 0H 35SO cm 1 UV spectrum (ethanol) max. 245 nm (0.12) / J 302 nm (0.03) // Va 1 “(4-Äiaino“ 3,5-âichlor-pnenyl) -2- / N- (1 “methyl-3-phenyl-propyl ) - irie -'- hylamino / ~ ethanol - hydrochloride .................... ... ^ ............. ^ _ ______ _ ______

Example 182

Made from 1 - (4-amino-3,5-aichlorophenyl) -2-y / N- (1-methyl-5 3-phenyl-propyl) -smino7-ethanol,? Ar aforr.aldah.yd and Sodium eyanborohydride in absolute ethanol analogous to Example 101. Melting point of the hydrochloride: 170-173 ° C.

! } "Example 183 1- (4-Ä5iino-3,5-dichlorophenyl) -2- £ N- (1-ir.ethy 1-3-phenyl-propyl) -10 pa, ogyl £ iaia, Q / - 'athanol' hydrochloride .Made from 1- (4-aino-3,5-dichlorophenyl) -2- / ÎÎ- (1-methyl-3-phenyï-propyl) -öiaino / -l * ethanol, propionaldehyde * and sodium cyanoborohydride analogous to Example 101. Oily hydrochloride.

-1 XK spectrum (methylene chloride): NH «3390 + 3490 cm 2ff) -1 15 NH ^ 2300 - 2400 cm OH 3590 + 3630 cm" 1 GV spectrum (ethanol) msx. 245 nm (0.12) Q 302 nm (0.03)

Example 184 - _ 20 Ti- [2- (4-Amino-3, S-dichloro-rhenyl) ™ “thyl / ™ N ~ (3-pbenyl-propyl) - y z - n-propylamine-hydroghlorld _________ _____ ___ _____ ____ ___

Prepared from N- ^ 2- (4-Ämino-3,5-dichloro-phsnyl) -äthyiy-3-phenyl-propyIsiüin, fropionaldehyde and sodium cyanoborohydride in absolute ethanol analogously to Example 101. Oily hydrochloride.

«· Λ 25 IR spectrum (methylene chloride): NH ^ 3390 + 3490 cm / NH © 2300 - 2400 cm" 1 f's \ -1 / \ OH 3600 + 3650 cm! ............ “........ ....... - Ï11 - W ~ Spsptrum (ethanol): 3 * ^ ax. 245 nm (0.17) 302 nm (0.05)

Example T 85 11 ™ / 2- (4-Aiaino-3,5-dichlorophenyl) -thyl / -N- (3-phsnyl-propyl) -5âthylamine hydrochloride _________ _______ 'Manufactured from N- / 2- ( 4 - Amino-3,5-dichlorophenyl) ethyl / -3-phenylpropylamine, acetaldehyde and sodium cyanoborohydride in absolute ». 0 ethanol analogous to Example 101. oily hydrochloride.

IR spectrum (ethylene chloride): 3390 + 3490 cm 1 10 NH vt) 2300 - 2400 cm “1 UV spectrum (ethanol) 245 nm (0.12) 302 nm (0.04)

Example '186 N- / 2- (4-amino-3,5-dichlorophenyl) ethyl / -N- (1-roethyl-3-phenyl-15 prooyl) ethylamine hydrochloride

Made from N- ^ 2- (4-amino-3,5-dichlorophenyl) ethyl / -N- (1- (/ ^ iaethyl-3-phenylpropyl) amine, acetaldehyde and sodium cyanoborohydride in absolute Ethanol analogous to Example 101. Oily hydrochloride.

20 IR spectrum (methylene chloride): 3390 τ 3490 cm 1 'UV spectrum (ethanol): Eax243> ra (0.11)' - 200 13A (0.04)

Example 187 1- (4-Axino ~ 3,5-dichlorophenyl) -2- ^ N- (1-methyl-2-phenoxy-ethyl) -25 ethylamino 7-ethanol hydrochloride

Made from 1- (i-arino-3,5-di-7h = or-rher.yl) _- 2- / N- n-juethyl- ................ . - ri2 - '

V

2-phenoxy-ethyl) ~ amino / ethanol, acetaldehyde and sodium cyanoborohydride in absolute ethanol analogous to Example 101 · oily hydrochloride.

I.Fv spectrum, (ethylene chloride): NH., 3390 + 34SO cm 1 - 5 SH * © 2320 - 2460 cm “1 OH 3SOO + 3630 cm" 1 DV spectrum (ethanol): aax. 248 nm (0, 12) 300 nm (0/03)

Example 188 \ J) '_ _ 10 1- (4-amino-3 “cyan-5-fluorophenyl) -2- / N- / 2- (3,4-dimethcxy-phe-nyl) -äthyi7-äthvlaminö ? -ethanol

Made from 1- (4-amino-3-cyan-5-fluorophenyl) -2- / N- / 2- (3,4-dimethoxyphenyl) ethyl / gmino / ethanol, acetaldehyde and Na- triisacyanborohydride in ethanol, analogous to Example 101. oil.

15 IR spectrum (methylene chloride); NH2 3390 + 3490 cm 1 CN 2205 cm "1 UV spectrum (ethanol): ^ max. 240'nm (shoulder; 0.16) 2S0 nm (0.04) 325 nm (0.06) u 20 Example 189 1 “(4-Aaiino-3-chloro-5-fluorophenyl) -2- / S- / 2- (3,4-ir.ethylenäicxy-: '' phencxy) -1-methyl-ethyl / -ethylamlnp / -SthanQl-hyärochlorld

Made from 1- (4-amino-3-chloro-5-fluorophenyl) -2- £ î- £ 2- (3,4-methylenedioxy-phenoxy) -1-methyl-ethyJL / -amino / -ethanol, 25 acetaldehyde and sodium cyanoborohydride in absolute ethanol analogous to Example 101. Oily hydrochloride.

............... ........ ~ ......... "" ........... - ~ Tl3. .......... ..... 'IR-Spsktrua (Ksthylenchlorid.): LîHj 3390 + 3490 cm 1' NH ® 2300 - 2450 cm "1 OH 3600 + 3630 cm" 1 UV spectrum ( Ethanol): ^ max. 243 nm (0.17) 5 237 nm (0.07)

Example 190 1- (4- £ jmino-3-bros-5-fluorophenyl) -2 - ^ - (l-msthyl ^ -phancxy- a ^ vl) “âthylamii? O /“ âtk5: ïï2l ______ O '' ” ';

Made from 1 - (4-amino-3-bromo-5-fluorophenyl) -2- / N- (1 -'10methyl-2-phenoxy-ethyl) - £ min (p-ethanol, acetaldehyde and sodium- cyanoborohydride in absolute ethanol analogous to Example 101. oil.

IE spectrum (methylsnchloride): KH2 3390 + 3490 cm ”1 UV spectrum (ethanol): ^ max. 240 nra (0.14) -, 280-290 nm (0.03) 15 Example 191 1 “(4-Amine-3-cyan-5-fluorophysny 1} -2- / ÏÏ- / J- (4th -methoxy-phenyl) -pro-ί'Λ? yl / ~ Sthylaiainç> / - âthanQi · -hydrochloride ____________

Made from 1- (4-amino-3 ~ cyan-5-flnor-ph3nyl) -2 - / :: - / 3- (4-rae-cncxy-phenyl) "propy <l ^ _aHi £ no /" ethanol, .Acetaldehyde and sodium 20-cyanoborohydride in absolute ethanol analogous to Example 101. Oily hydrochloride.

ÏR ~ Spsptrum (I4ethylanohioiHd) s RH- 3350 4- 3 ^ 90 cm ”1“ --1 NH v 2300 - 2500 cm CN 2205 cm “1 25 -1 J 0H 3590 + 3680 cm ÜV-Spsptrum (ethanol); 248 nm (0.11) 280 nm (0.03) / 320 nm (0.06) ---------------------------- ----------------- - .....- · Γ174 _ - -

Example 192 lî- £ 2- (4 “Amino-3,5-dichloro-] 'henyl) -ethy 1 / -11- ^ 3- (4 — f.luor-phsnyl) -propyffi-benzylamine-hyàrocb 1 orid _______________

Made from N- / 2- (4 ~ Ainino-3f5-dichlorophenyl) ethyl / -N- / 3-5 (4-fluorophenyl) propyfp-amine, benzaldehyde and sodium cyanoborohydride in absolute ethanol as in the example 101.

Melting point of the hydrochloride: 118-120 ° C.

('* Example 193 K- / 2- (4-Ajrdno-3,5-dichlorophenyl) ethyi / “K- / 3-- (4-fluorophenyl) - 1 o py ^ nvlT-n-propylamine -hydroChlorid ______________________ - 'Made from (4-ar. ino-3,5-dichlorophenyl) -sthyV-N - / _ 3- (4-fluorophenyl) propyi? -, - in, propionaldehyde, and sodium cyanide Boi'hydrid in absolute Ät / ^ ol analogously to Example 101.

Melting point of the hydrochloride: 130-133 C.

Ί5 Example 194 0 u-ß- (4- £ mino-3,5-dichloro? Henyl) ethyl J-N- / 3- (4-fluorophenyl) -

Made from N- / 2- (4-.V inc-3,5-diehlor-phenyl) -äthyjJ-N - /! - '(4-fluorophenyl) -propyi7 -.-- in, acetaldehyde, molecular sieve 3 S and potassium cyanoborohydride in abso_Uuem hetnc.iiol - "aiog.-Tispisl 101. Melting point of the hydrochloride: 182-134 ° C (ser.).

%

Example 195 ........ .................- N - / 2- (4-Amino-3,5-dichlorophenyl) ethyl / ~ N- / 3- (4- £ 1uor-phany 1) -propyï / -isopropy1- a: · ain ~ hyÆro ch 1 orid _ '

Made from N- £ 2- (4-amino-3,5-dichlorophenyl) ethyl / -N- / 3-'5 (4-fluorophenyl) propyï7-amine, acetone, molecular sieve 3% and sodium cyanoborohydride in absolute methanol analogous to Example 101. Melting point of the hydrochloride: 182-184 ° C. (dec.).

o 3a.igp.iel 196 1- (4- £ mino-3,5-dichloro-ph.enyl) -2- ^ N- / 3- (4 - fluoro-phany1) -prcpyl / -10 2-phenylathvlagting / -ethanol hydrochloride __ __ - · Made from 1- (4-amino-3,5-dichlorophenyl) -2- / N- / 3- (4-fiuor- phsny 1) -propyl / -amino / -ethanol , Phenylacetaldehyde and Katrium-cyasborhydrid in absolute ethanol analogously to example 101. Amorphous hydrochloride.

15 IR spectrum (methylene chloride): NHn 3390 + 3490 cm ^ T +) -1 NH ^ 2300 - 2500 cm CH 3590 + 3680 cm’1 OÜV spectrum (ethanol): max. 243 nm (0.11) 300 nm (0.04). .20 Example 197 1- (4-amino-3,5-dichlorophenyl) -2 - /: .-- / 3- {4-fluoro-pkanyl) propyl / -benzylaminoj-ethanol hydrochloride - __________ _________________

Made from 1- (4-amino-3,5-dichlorophenyl) -2- / N- / 3- (4-fluorophenyl) propyl / amino / ethanol, ssnzaldehyde and Katriumcyanbor-25 hydride in absolute Ethanol analogous to example 101.

Melting point of the hydrochloride: 132-134 ° C (dec.).

/ ----------- - .16 - .................... '

Example 138 1- (4-Amino-3,5-dichlorophenyl) -2- / N- / 3- (4- £ luor-phenyl) propyl / -n-propylamine / ethanol hydrochloride ---- 1 | "d * ui hihi IM-BJUM« »imjiwi« »IIIMI> iiw minina t« · * ·? ··· 1 · »--- Jit'ij i.rnn; r.-M», = «« .. J vs3, i -.:.-_ -> -.> - », - ... r ~ - -, - - -,

Made from 1- (4-amino-3,5-dichlorophanyl) (4-fluoro-5 phenyl) prop yl / aialno / ethanol, propicnaldehyde and sodium cyanoborohydride in absolute ethanol analogous to Example 101.

Melting point of the hydrochloride: 136-138 ° C (dec.).

Example 199 1 "(4-amino-3,5-dichloro-pnsnyl) -2- / N- / 3- (4-fluoro-pbenyl) propyl / -10 cthyl £ minp / ethanol hydrochloride ____________________ _____

Made from 1- (4-amino-3,5-dichlorophenyl) -2- / N- / 3- (4-fluorophenyl) propyl / araino / ethanol, acetaldehyde and. Natriux & cyahhorliydrid in absolute ethanol analogous to Example 101.

Melting point of the hydrochloride: 130-134 ° C.

15 Example 200 o 1- (4-amino-3 f 5-dichlorophenyl) -2- / N- (3-phenyl-propyl) -2 ~ phenyl-ethylaminoyethanol hydrochloride

Prepared from 1- (4-aminc-3,5-dichlorophenyl) -2- / N- (3-phenyl-propyl) amino / ethanol, phenylacetaldehyde and sodium cyanoboramate analogously from such pure ethanol Example 101. Amorphous hydrochloride.

-1 IR spectrum (methylene chloride): NH "3390 + 3490 cm NH ^ 2300 - 2500 cm 0H 3590 + 36SO cm" 1 25 UV spectrum (ethanol) max. 243 ran (0.12) 300 nm (0.04) ......... - 117 - ...........'.......... "

Example 201 1- (4-Äiaino-3, 5-âichior-pheny1) “2“ / N ~ / 3- (4-fluoro-phenyl) -propylj · -isopropylsüiino / ~ gfchanol ~ hydrochloride ^ _ «, = ________

Made from 1- (4-amino-3,5-dichlorophenyl) -2- / N ~ £ 3- (4-fluoro-5 phenyl) propyl / aissino / ethanol, acetone, molecular sieve 3 8th and Sodium cyanoborohydride in absolute methanol analogous to Example 101. Melting point of the hydrochloride: 80-35 ° C (ser.).

u Example 202 1 - (4-JtEino-3,5-dichloro-phsnyl) --2- / N- (1 -methyl-3-phsny1-propyl} - 10 Sthyl amlno / ^ äthanol _ _____

Made from 1- (4- £ roino-3,5-dichicr-pher.yl) -2- £ K- (1 - sethyl-S-phenyl-prcpyl) - £ mino / ** äthariOl, Icatnldshyd, Mslsisb 3 8 Pud ITatriumeyar-Horhydrid in absolute ethanol analogously to Example 101. · Oil.

15 IR spectrum (methylene chloride): NH ^ 3390 + 3490 cm OV spectrum (ethanol): max. 245 nm (0.13) 300 nm "(0.03) 0

Example 203 1- (4-Dimethylamino-3,5-dichloro-phenyl) -2- / îï- (3-phenyl-1-methyl-20 propyl) -methylaminpyethanol _________ ______ __ _______

Made from 1- (4-Äm.ino-3,5-dichlorophenyl) -2- / S “(3-ph = uyl- 1-methyl-propyl) amino / ethanol, formaldehyde and sodium cyanoborohydride in absolute ethanol analogous to Example 101. oil. LE spectrum (synthetic chloride): 0H 3600 d 3680 cm 25 N-Älkyl 2300 cm “1 UV spectrum (ethanol) max. 275 nm (0.03)

A

-113 -

Example 204 1- (4-aminc-3,5-dichlorophany1) -2- £ N- (3-phenyl “PrQpyl) banzyl-gmrno / —ätilcUQl__ __ __ ____ __________________ -........ .

Prepared from 1- (4-amino-3,5-dichlorophenyl) "* 2- £ N- (3-phenyl-5-propyl) -amix ^ -ätfcanol, benzaldehyde and natrinacyahborohydride in absolute ethanol analogously to Example 101. oil.

IR spectrum (methyl chloride): NH2 3390 + 3490 cm OH 3600 + 3630 cm ^ üV spectrum (ethanol) max. 245 nm (0.12) O 10 300 nm (0.03)

Example 205 1- (4 “Araino-3,5-dichloro-pb eny 1) -2- / p- £ 3 ~ (4-methylsulfinyl-phenyl) - '·: · propy, 1. / - am 1 n q? - ä tha η ο 1 _ _ ___________ esa® 1.5 g (0.0039 mol) 1- (4-amino-3,5-dichlorophenyl) -2- / N- / 3- (4-15 methylsulfenylphenyl ) -propyl / -amino / -ethanol and 639 mg (0.0078 mol) of anhydrous sodium acetate are dissolved in 60 ml of 50 liter acetic acid. A solution of 622 mg (0.0039 mol) of bromine in 3 ml of 50% acetic acid is slowly added dropwise to this solution while stirring at room temperature. When the addition is complete, the light brown solution is left to stand at room temperature for one hour and then poured into water. While cooling with sis, conc. Ammonia made alkaline to pH 8.5 and extracted exhaustively with methylene chloride. The combined methylene chloride extracts ’.. are dried over sodium sulfate and evaporated to dryness under vacuum 25. The residue is crystallized from Mathanol / Xther. Colorless crystals.

Melting point: 127-12 9 ° C.

/ n rsxspiel 206 - 119 - 1 "(4-Amino-3,5-dichlorophenyl) -2- [11- / 2- (4-methylsulfonylpheny1) - propyl / -sminc ^ -äidianol · ____ ______

Made from 4 '* -ΐΛΰ1ηο - 3', 5 '-dichloroacetic, selenic dicide, 5 3- (4 -methylsulfenylpheny1) propylamine and sodium borohydride analogous to Example 5.

Melting point: 128-130 ° C.

• j Example 107 1- (4 "ares; inc-3,5-dichlorophenyl) -2- £ * - £ 3- {4-inethylsulfinylphenyl) - 10 pro3yl / -ixethvlami; ip /" - Itha.nQl _______________ ______________

Made from 1 - (4 -liaino-S, 5-dichlorophenyl) -2- / N- / 3- (4-methvl-: sulfinyl “-phenyl) -prc-pyl7” Knisp / ^ äthBiiol, 'Paraforsïaldehyd · . and Katriumcyanborkydrid in methanol analogously to Example 101. Schaan.

IR spectrum. (Machylene chloride): OH 3660 + 3600 cm 1 15 NH2 3490 + 3390 cm “1 SO 1050 cm“ 1 ÜV spectrum (ethanol): max. 242 nm (0.16) Çy. 300 nm (0.03)

Example 208 20 1 - (4-Amino-3,5-dichlorophenyl) (4-methyl suif enyl-phenyl) - • _ ^ qpyî / yms ^ i "lôïûinp / ^ i / dh: -:.: - iOl __ _

Prepared from 1- (4-amino-3,5-dichlorophenyl) -2- ^ N- / 3- (4-methyl-sulfenyl-phenyl) -propyjy-aming / -ethaiiol, paraformaldehyde and potassium cyanoborohydride in methanol analogous to Example 101. Colorless Ql. 25 IR spectrum (methylene chloride): 0H 3690 + 3590 cm 1 A NH2 3490 + 3390 cm “1 / ln ........... - 120 - ιοί) ï i :: ax. 245 nm (0.23) 295-300 r-m (0.04)

Example 209 1 = (4-amino-3,5-dichlorophenyl) "2- / îî-A3- (4-chlorophenyl) -prcpylÿ-; 5 n-propylamino / ethanol _____ ____________________________

Prepared in 1 - (4-amine-3, S-dichloro-pkanyl) (4-chloro-pheayl) -propyl / “ai3ino / -ethanol, propionaldehyde and sodium (4 ^ cyanoborohydride in ethanol analogously to Example 101.01.

IR spectrum (methylene chloride): NH „3390, 3490 cm 1 • in ^ - -1, u arom. C = C 1620 cm W spectrum (ethanol): max. 243 nm (0.13) 300 ran (0.04) '- Example 210 1- (4-bimethylamine-3,5-dichlorophenyl) -2-methyl-2- / N- / 3- (4-15 mathoxy-phsnyl) -procyl / -; r.ethyl £ mino / ~ § hhanol ('y Made from 1- (4-amino-3,5-dichlorophenyl) -2-iT; ethyl-2- / N- / 3- (4-methoxy-pheny 1) -propy3y-? Jmino / -äthar; ol, parafonnaldehyde. And sodium cyanoborohydride in ethanol at pH 3-7.5 as in Example 101. Oil.

“1 20 TR spectrum (methylene chloride): 0H 3590 cm no NH, NH2; aroma C = C 1510 cm “1. * ÜV-Spektnun (ethanol): max. 243 nm (0.20) 278 nm (0.06) / f '\ ......... ....... ................ ....... - 1 ^ 1 - *

Example · 211 '. · 1 “(4-benzylamino-3,5-dichlorophenyl) -2- / ÏÏ- / 3- (4-chlorophenyl) --propyl / -smino / -« tbanol · .Made from 1- (4th -Amino ~ 3,5-dichlorophenyl) -2 - / N- / 3- (4-ehlor-5-plienyl) -propyÎ7 "£ Hino / ~ gthanolf Benzaldshyd and natrius cyano borohydride in ethanol analogously to Example 101.

Base melting point: S5-95 ° C.

ο

Example 212 1 - {4-Imino-3,5-Öichlcr-phanyl) -2- / Ν- £ 3- (4-chlorophenyl) propyi / «· 10 bsnzyla-ainoj-ethanol-hydroohlorld _________

Eergs is made of 1- (4-amino-3,5-dichlorophenyl) -2- / N- / 3- (4-chloro-.i mtm warn · * 1 T * m% ï ·· ** phsnyl) » propyl / "CU.U i no / -ethanol, Bsnsalcehyd and Katriumcyanbor-hydride in ethanol analogously to Example 101.

Melting point of the hydrochloride: 110-114 ° C.

15 Example 213

O

1- (4-amino-3,5-dichlorophenyl) -2- / N- / 3- (4-chlorophenyl) propyl “ethyl5mino / ätharjol ___________________

Made from 1- (4-amino-3,5-dichlorophenyl) -2- / N- / 3- (4-chloro-phsnyl) -prop ^ / - amino / ethanol, acetaldehyde and sodium cyanohydrate Ethanol analogous to example 101. oil.

IR spectrum (methylene chloride}: NH_ 3390, 3490 cm ^ '"z -1 arcm. C ~ C 16z0 cm irz-Spskciurti (ethanol): \ max. 244 nm (0.13) / 300 nm (0.04) ..... '- 122 -

Example 214 H- / 2- (4-amino-3,5-diehlor-phenyl) -ethyiy-N - / 3- (4-chlorophenyl) -pr opy ί7 -methy1 am in ^ _ _______

Made from N- / 2- (4-amino-3,5-dichlorophenyl) ethyl / “3- (4 ~ 5 chlorophenyl) propylamine, paraformaldehyde and sodium cyanohydride in methanol analogously to Example 101. Oil.

hüR spectrum (ethylene chloride); NH0 3390, 3490 cm ^ z -1 aroma C = C 1615 cm DV-Spskfcrum (ethanol): max. 241 nm (0.10) {<J 10 300 nm (0.04)

Beisoiel_ 21 5 1- (4-amine-3,5-dichlorophenyl) -2 ~ / ß- / 3- (4-chlorophenyl) propy17- 2-phenylethyl-a "iinp7, ~ äthanor-hydrochloride _ .

Made from 1- (4-amino-3,5-dichlorophenyl) -2- / N- <£ 3- (4-chloro-15 phenvl) propyl7-5mino7-ethanol, phenylacetaldehyde and sodium cyanoborohydride in ethanol analogously Example 101.

Melting point of the hydrochloride: 103-109 ° C (dec.).

O

Example 216 1- (4-Amino-3,5-di chlorophenyl) -2- / N- £ 3- (4-chlorophenyl) propy17-20 methylamine> 7-ethanol-chlorochloride ^ _______________ _______ _ ___

Made from 1 - (4- £ mino-3,5-dichlorophenyl) -2- £ N- £ 3- (4-chlorophenyl) propyl7-aniino7 ~ ethanol, paraformalcehyd and sodium cyanoborohydride in ethanol as in the example 101.

Melting point of the hydrochloride: 85-100 ° C (decomp.).

Example 217 1 · {3-chloro-4-piperidino-phenyl) -2- / N- / 3- (4-methoxy-phenyl), pyl7 "mefchylaminpV-äfchanol-hydrociiloride _______ ___

Prepared from 3'-chloro-4'-piperidino-2- / Ü- / 3- (4-methoxy-phenyl) -5 propyl / ~ n \ ethylamino / -acetophenone and sodium borohydride in methanol water analogously to Example 1. oily hydrochloride.

-I-R spectrum (methylene chloride): OH 3600 0111-1 OCH- 2840 cm ”1 Jê) -1

Nff- '2300-2700 cm' (3 ^ W spectrum (ethanol): ^ max. 258 nm (0.12) 283 nm (shoulder; 0.05)

Example 218: 1 - (4- & aino-3,5-dichlorophenyl) -2 ~ / k- / 3- (3-methoxy-phanyl) -pre- DVÎ7-ami: · .0 / -Sthanol '____ 15 Made from 4'-ajnino-3 ', 5'-dichloro-acetophenone, selenaioxad, 3- (3-methoxy-phenyl) -propylamine and Watriumoornycrid analogously to Example 5.

φ Melting point: 124 ° C.

Example 219 20 1- (4-Amino-3,5-dichloro-pher.yl) -2- / N- / 3- (3-rethoxy-phenyl '-pro-

Made from 1- (4-amino-3,5-dichlorophenyl) -2- / N- / 3- *: -reth-oxy-phsnyl) -propyl / -amino / -ethanol, acetaldehyde and Watro—- I cvanborhyorid in methanol analogously to Example 101. Oil.

^ -1! 25 IR spectrum (methylene chloride): OH 3580 cm ^ 'HH2 3490 + 3390 cm "1 I' OCH ^ 2830 cm. '' 'Ί2 & Γ- .uV spectrum (ethanol): max. 247 nm (0.06) 300 nm (0.04)

Example 220, 1- (4-Airdno-3,5-dichlorophenyl) -2- / N- / 3- (3-msthcxy-phenyl) propyl / · - 5 methylainino / ethanol ____________

Made from 1- (4- £ jriino-3,5-dichlorophanyl) -2- ^ N- £ 3- (3-xneth-oxy-phenyl) propyl / amino / ethanol, paraformaldehyde and sodium

N

_cyanoborohydride in methanol analogous to Example 101. Oil.

IR spectrum (methylene chloride): OH 3680 + 3620 cm 1 10 KH2 3490 +3390 cm “1 öCH3 2840 cm” 1 CV spectrum (ethanol) max. 246 nm (0.15) 300 nm (0.04) * ». *

Example 221 151- (3,5-Dichlcr-4-isopropylamino-phenyl) -2- ^ N- £ 3- (3-methoxy-pheny 1) -propy 1 / - i sopr ony 1 amiη ο / - M than ο 1_________________________

Prepared from 1- (4-amino-3,5-dichlorophenyl) -2- / N- £ 3- (3-xaethoxyphenyl) propyl / amino / ethanol, acetone and sodium cyanoborohydride in methanol analogously Example 101. Oil.

20 IR spectrum (methylene chloride): OH 3600 cm NH 3350 cm "1 - - 0CE3 2840 cm" 1 OV spectrum (ethanol): Ov max. 250 nm (0.12) 278-280 nm (0.03) K \

Example 222 - 125 ”-; 1 »(4-Aiïiino-3,5-dichlorophenyl) -2- / ÏÏ- / J- (4-chlorophenyl) -propylj“ isopropy lara Ino / - Stha nol ^ Made from 1 - (4 “A_mino-3 , 5-dichlorophenyl) -2- / N- / 3- (4-chloro-5 phenyl) -propyjtf-amino / ethaol, acetone and sodium cyanohydride in ethanol analogously to Example 101. oil.

-XS - spectrum (methylene chloride): NH9 3350 + 3480 cm ^ 2 -1 aroma. C = C 1615 cm ^ I'IMR spectrum (CDCl ^ / D ^ O): aroma. H 7.0-7.4 ppm (m; SH) O 10 ^ CK-OH 4.4 ppm (dd; 1H) -ChC 3.0 ppm (dd? 1H) aliph. CH2 2.3-2.7 ppm (m; 6H) 1.6-2.0 ppm ίίΰ? ^ Η) i soprcpyl-CH3 0.8-1.2 ppm ^ 15 - (dd; 6H)

Example 223 1- (4- & rdno-3,5-dichlorophenyl) -2- / N- / 3- (4-chlorophenyl) propyl / 'allylamino / ethanol _____________ O · _ _:

Made from 1- (4 ~ amino-3,5-dichlorophenyl) -2- / N- / 3- (4-chloro-20 phenyl) propyl / amino / ethanol, allyl bromide and triethylamine as in Example 13. oil.

IR spectrum (methylene chloride): NH2 3380 + 3480 cm ^ aroma. C ~ C 1610 cm ^ KMR spectrum (CS> C13 / D20): aroma.H 7.0-7.4 ppm (m; 6H) 25 olef .H 5.5-6.1 ppm (m; 1H) 5.0-5.3 ppm (m; 2H) ^ CH-GH 4.3-4.7 ppm (dd; 1H) ^ .N-CH2 - 2.3-3.5 ppm (m; 23) / 'aliph.-CH2 “2.2-2.7 ppm (m; 6H) 3®' \ 1.5-2.0 ppm (m; 2H ) ------ '"*' ........” AC '------— · --------- “Ί î ^ o -

Example 224 N- / 2- (4 "Araino-3,5-dichlorophenyl) ethyl 7-N ~ 3- (4-chlorophenyl} - Made as N- ^ 2- (4-amino-3, 5- dichlorophenyl) ethyl / -3- (4- - * 5 chlorophenyl) propylamine, allyl bromide and triethylamine analogously to Example 13. oil.

-EE spectrum (methylene chloride): NH2 3380 + 3480 cm "" ^ arom. CC 1610 cm NMR spectrum (CDC13 / D20): arom.H 6.9-7.4 ppm (m; 6H) 10 olef.H 5.6-6.1 ppm (m; 1H) 5.0-5.3 ppm (m; 2H) ^ ï-CH2- 3.0-3.3 ppm (d; 2H) aliphatic-CH2 “2 , 7-3.3 ppm (m; SH) 1.3-1.9 pp-m (m; 2H) 15 Example 225 K- ^ 2- (4-amino-3,5-dichlorophenyl) -1 -methyl “ethyl / -Ni £ 4- (4-methcxy-phsnyl) -butylZ-mathyl amine --------- ----— _______ ________ Q Made from 4'-amino-3 ', 51 "Dichloro-propiophenone, N- / 4- (4-methoxy-phenyl) -butyl / -methylamine and Eatrituucyanhorhyarid sna- 20 log Example 101. Oil. ^ IR spectrum (methylene chloride): NH2 33o0 + 3480 cm aroma. C ~ C 1610 cm S A.

üV-Spekfcrum (ethanol): Λ r.ax. 245 rjn (0.13) - 280 nm (wide? 0.04) 25 300 nm (wide; 0.04) / ~ \ • \

Example 22J [.......... ".......- 127 - ~ - N- / 2- (4-Amino-3,5-dichloropheny1)" ethyl / -N- / _3- (4-msthoxy-phenyl) -1-methyl-propy! / “5thylamine __ ^ ^

Made from N- / 2- (4-arfdno-3,5-dichlorophenyl) ethyl7-N ™ / 3-5 (4-hydroxyphenyl) -1-methylpropyl / ethylamine in tetrahydrofuran with sodium hydroxide solution and dimethyl sulfate as in Example 13.

_BJLe cleaning is carried out using aluminum oxide (neutral, activity level I) and the eluent mixture Sther: petroleum ether = 1: 1.5. oil.

0 10 3rd: C 63.79 H 7.14 CI 17.94 N 7.09

Found: 63.17 7.09 17.90 7.15

Example 227? '' Κ- / Ί! - (4-Amino-3,5-dichicr-phenyl) - ^ thy ^ -N-Zl jl-Äiniathyl-SH- hy droxy-Phenyl) -propyl / -methy 1 ~: ~ ln _____________ _ 15 Su of a solution of 3 g (0.0075 mol) of 1- (4-amino-3,5-dichlorophenyl) -2- / N- / T, l-dimethyl-3- (4-hydrexy-phsnyl ) -propyl / · -msthyl-amino / -ethanol in 12 ml trifluoroacetic acid is added dropwise while stirring Λ φ at -10 c 1.8 ml (0.018 mol) pyridine-borane.

After removal of the cooling, the reaction solution 20 warms up to room temperature within 30 minutes and is then heated on the steam bath with stirring for 60 minutes. After evaporation of the trifluoroacetic acid on a rotary evaporator at 50 ° C

• In vacuo, the evaporation residue is mixed with 40 ml of 2N sodium hydroxide solution and heated for 30 minutes at 120 ° C. with stirring. After cooling, the? .E-25 action mixture is carefully acidified with concentrated hydrochloric acid and mixed with concentrated ammonia until a basic reaction is carried out and then extracted twice with 75 ml of jitter each. The Xtfcsr extracts obtained are washed with 2 x 50 ml of water, dried after combining with magnesium sulfate 50 and concentrated to dryness in vacuo on a rotary vaporizer. The ceramics residue is purified over Kieselgal 50 v -— \ L '- 123 - (Kacherey and Hagel 70-230 rnesh, AS TM) and the 2 lutant methylene chloride id / Methano1 = 2: 1. Post-cleaning is carried out using aluminum oxide (neutral, activity level III). Aether / n-hexane »2: 1 is used as EXuens. The oily evaporation residue obtained crystallizes after a short time.

Melting point: 122-124 ° C.

- Example 228 N- / 2- (4-amino-3,5-dichloropheny1) ethyl / -N- £ 3- (4-hydr hrf · 5 ny 1) -1 -siethyl-prGpyjy-ethylamine 10 from 41 ”amino-2-brcm-31, 5 1-dichloroacetophenone, N- ^ 3- (4-hydroxy-phsnyl) -1-methyl-propyl / -ethylaiain, sodium carbonate in aqueous tetrahydrofuran and subsequent reaction of the reaction product obtained with pyridine-soran in - trifluoroacetic acid analogous to example 227. The cleaning is carried out over aluminum oxide (neutral, activity level III). Ather / petroleum ether = 2: 1 is used as Sluans, oil.

IS spectrum (methylene chloride): OH 3530 cm 1 NH0 3480 + 3390 cm-1 ^ —1 CH2, CH3 2960 + 2930 + 2860 cm O ^ N-alkyl 2810 cm 1 C = C 1585 + 1510 + 1485 cm “1. UV spectrum (ethanol): inax. 241 nm (shoulder; 0.28) 280-302 nm (0.08) (ethanol + Κ0Η): Ov max. 241 nm (0.56) 25 298 nm (0.17)

Example 229 1- (4-Amino-3,5-dichlorophanyl) 1-dimethyl-3- (4-hydroxyphenyl) propyl / -raa thy 1 amlnp / -ätlnanol __

Manufactured from 4 '-amino- 2-brcm-31.51 -dichloro-acetovlienone, / 7 / s --- N "“ “..... .....

- 129 ..... '' N- / J, 1 -dimsthyl-3- (4-hydraxy-pkenyl) -propyl ^ -ïusthylaiain, Na-; triu: -. * E & rhGr «at and subsequent reduction with sodium borohydride in wäirsrigsni Tetrahydrofuran analogous to Example 3, the pre- and N & Ehrsinigimg takes place over silica gel 60 (Kachêrey and hail, 5 70 = 230 Kesh, ASTM). Xthar / tetrahydrofuran - 3: 1 and methylene chloride / Mathanol / conc. Ammonia = 30: 1: 0.3 used.

Melting point 155-15S ° C.

«-" V

u 5-3.1 game 250 10.1- (4-Ajnino-3,5-dichloro-phsnyl) ~ 2- £ n- £ T, 1 -dimsthyl-3- (4-hydrcxy-. · '-phenyl) ~ $ L · ,,, -, ~ j, n— ^ i “Made from 41-amina-2-brost-3 *, 5 * -dichloro-acetophenone, 1,1-dimethyl-3- (4-hydroxy-phenyl) - propylarain, K & triumcarbonate and reduction with sodium borohydride in aqueous tetrahydro-15 furan analogously to Example 3. The cleaning is carried out using Kissalgel .q SO (Mscherey and Nagel, 70-230 mesh, ASTM). A mixture of methylene chloride / mathanol / conc. Ammonia = .25: 1: 0.2 used.

Melting point: 142-144 ° C.

20 Example 251 ÎJ- / 3- (4-chlorophenyl) propyl? -1 »- # - <3,5- <Jichlor-4-isopropyl-gjnino-phsnvX) ------___--—

Production of Κ- / Γ- (4-kilno-3,5-dichlorophenyl) -thyî / - / 3-; 4- - 130-chlorophenyl) -propyî? Arain, acetone and natrium-cyenborohydride analogously to Example 101. Oil .

MMR spectrum (CDC13): aroma H 7-7.3 ppm (ra? 6H)> CH- 3.5-4.1 ppm (m; 1H) 5> CH- approx. 3 ppm (m; 1H) aliph. H 2.3-2.7 ppm (m; 8H) 1.5-2.0 ppm (m; 2H) 0.9-1.3 ppm (dd; 12H); Example 232 10 N- / 2- (4-amino-3,5-dichlorophenyl) ethyl 7-K- (3-phenyl-1-methyl-ppouyl) raethvle »sin _____________________________________________—

Prepared eus N- / 2- (4-amino-3,5-dichloro-phenyl) ~ ätbyi / -M- (3-phenyl-1-œetbyl-propyl) -amine, paraformaldehyde and Katriumcyanorbohydrid as in Example 101 Oily hydrochloride · •. , _ ί 15 IR spectrum (ethylene chloride): MHg 3330 + 3 ^ 90 cm CK2 2930 cm · “1 UV spectrum (ethanol): ^ sax. 243 ns (0.12) 300 ran (0.04)

Example 253 20 n- ^ 2- (4 ~ liaiiio-3, ohlor-phenyl) ~ £ ϊΥιγ £ 1-α - (3-pkenyl-1 ~ ethyl ~ nronyl) -n-propy: lMiS ----_. ... »-----"

Prepared from H- / 2- (4-amino-3,5-dichloro-phenyl) »M · thylJ-K- (3-phenyl-1-methyl-propyl) -asine, Fropiozsldehyd and Katriuacyan-borohydride analogously to Example 101. oily hydrochloride.

25 IR spectrum (methylene chloride): KH2 3390 + 3490 cm ”1 CH2 2930 cm" 1 UV spectrum (ethanol);, rx. 245 nm (0.11) s 3OO nm (0.04) L ^ '

Example A

- 131 -

25 mg tablets of 1- (4-amino-3,5-diehlorophenyl) -2- / N- (3-phs-nyl-propyl) ~ 2 “propylämiaQ / - gthanol” -Iiydrc <chloride

Composition: 5 1 tablet contains:

Active substance 25.0 mg - corn starch 30.0 mg

Spleen sugar 61.5mg

Geranne 3.0 mg ^ 10 magnesium starsate 0.5 mg 120.0 mg

Active ingredient, corn starch and milk sugar are mixed, moistened evenly with the aqueous gelatin gel and granulated. 15 After drying in a circulating air drying cabinet and sieving (1.5 mm clear sieve width), the lubricant is added. The ready-to-press mixture thus obtained is compressed into tablets.

*

Shape: biplane with a single-string notch and Q 20 facet on both sides. Diameter: 7 mm

Weight: 120 mg

Example B

I i.l. % «.. Il I

Dragées of 10 mg 1 - (4-amino-3,5-dichlorophenyl) -2- / N- (3-phenyl-propyl) -2-propylamino / ethanol hydrochloride 25 1 coated tablet contains:

Active substance 10.0 mg

Corn starch 35.0 mg

Milk sugar 71.5 mg <..........................

- 132 -

Gelatin 3.0 mg

Magnesium stearate ____ 0/5 mg 120.0: ng

Production: 5 Analogous to example A.

Pressing to 7 mm diameter cores and 6 mm bulge reduction.

The cores thus produced are coated in a coating pan with a sugar coating paste up to a weight of 160 mg. The mixture is then further coated with pure sugar syrup up to 165 mg and the coatings thus obtained are polished. .

Example C

- p

: Capsules of 20 mg 1- (4-Am ± no-3,5-dichloro-phsr.yl) -2- ^ N- (3-phenyl-propvl) -2-propylsmino / ethanol-hydrochloride contains 15 1 capsule :

Active substance 20.0 mg

Milk sugar pulp. 114.0 mg q Maize starch 60.0 mg Soluble starch 5 fo rog 20 Magnesium stearate 1 0 mc 200.0 mg

Production ^ - The active ingredient is mixed homogeneously with the remaining kilos and filled into size 2 capsules in a capsule filling machine.

Channel fill weight: 200 ο »/

Example D

- 133 - ~~ ~

Drops of 20 mg 1- (4-Aïrdno-3,5-dichlorophenyl) -2- ^ Ν- (* ι! * '- ΑΥ ^ · propyl) -2-propylamingy-ethanoi-hydrochloride per 5 ml - 100 ml drip solution contain: 5 active substance 0.4 g

Hyroxyethyl cellulose 0.15 g -: - tartaric acid 0.1 g

Sorbitol solution 70% dry matter 30.0 g

Glycerin 10.0 g O 10 benzoic acid 0.15 g

Distilled water to 100.0 ml

Manufacturing:

There. Water is heated to 70 ° C. Herein under | i,! "* · εη- * *" ^ 4- - the hyroxyethyl cellulose benzoic acid and tartaric acid · ι · 1 »3 It is cooled to room temperature and cas and the sorbitol solution are added with stirring. In the case of RauiM "’ r _,. Solution tur, the active ingredient is added and stirred until it is completely <’. Afterwards, the juice is evacuated to vent the juice i1’ "’

O

20 Example Ξ

Suppositories of 50 mg 1- (4-Ajnino-3,5 ~ dichlorophenyl) * phanyl-propvl) -2-propyl-ming / -Mthanol - hycrochloride "-: 1 suppository contains:

Active substance 0.05 Ί 25 hard fat (e.g. WTitepsol W 45) 1/65 1.70 ** i - 134 -

Manufacturing:

The hard fat is melted. The ground active substance is dispersed in the melt at 38 ° C. It is cooled to 35 ° C and poured into weakly pre-cooled suppository forms.

5s suppository weight: 1.7 g.

- Example F

Ampoules of 20 mg 1- (4-amino-3,5-dichlorophenyl) -2- ^ 5- (3-phenyl- '% -propyl) -2-propylamino / -ethanol-hvdrocnlorid__ 1 ampoule contains: 10 active substances 20.0 mg

Citric acid 12.5 mg. Sodium monohydrogen phosphate 37.5 mg: - Sorbitol. 36.5 img

Water for injections ad 5.0 ml 15 Preparation:

In a calibrated preparation vessel, water is placed for injections and the active ingredient, lemon

kJ

Acid, sodium monohydrogen phosphate and sorbitol dissolved at room temperature.

After filling up to the calibration mark, it is filtered through a membrane filter and filled into cleaned and sterilized ampoules with inert gas.

Sterilization: 20 minutes at 121 ° C.

A '· /

Claims (41)

1. Heue phenylalkylamines of the general formula R, R '/ R5 2x ^ r \ ^ A-CH-N, (I) o TT «/ v R 3 1. in the!' r is a hydroxyl group, an amino group optionally substituted by a t * j I% "· 5 kanoyl group with 1 to 3 carbonstorfafcoirian or a" · ^ oxycarbonyl group with a total of 2 to 4 carbon- 'i> ~ 1 -, an alkylamino or di. * | aminogruppa, each alkyl part containing 1 to 3 carbon atoms and each being substituted by a phenyl group '10, 1 * 2 and, which may be the same or different, Ha5 -, atoms, trifluoromethyl, cyano or kitro groups 00of * “* ''" r of the radicals R ^ or R ^ also a hydrogen atom, _. R4 is a hydrogen atom or an alkyl group with 1 to J | - 15 carbon atoms, j, * = * 1 _ p R a water atom, a straight-chain or branched: · I ^ _ 'alkyl group with 1 to 4 carbon atoms, a cyclo - ~ | group with 3 to 6 carbon atoms, an alkenylg '- ?? - | with 2 to 5 carbon atoms or an aralkyl group.- · = - * 1'- -J Î20 7 to 10 carbon atoms, A the methylene, ethylene or hydroxymethylene group B a group of the formulas | - 156 - '............................... ".........- - - - ; -% -CH- (CH2 R7 or - ~ <2C R 7 “where Rg is a hydrogen or halogen atom, a hydroxy group / an alkoxy group with 1 to 3 carbon atoms, optionally substituted by a phenyl group, an alkylsulfenyl-5 or alkylsulfir .y I group each having 1 to 3 carbon atoms, Ry a. hydrogen "atom, one hydroxyl group or an alkoxy group with 1 bir- 3 carbon atoms or Rg and together the methylene group, 10 R "is a hydrogen atom or an alkyl group having 1 to 3 carbon atoms, D is an oxygen or sulfur atom, a sulfinyl or sulfonyl group, n is the number 1 or 2 and 15. one is optionally by one or two alkyl groups each 1 to 3 Fhilenstoff fatc-men substituted straight-chain A-alkylene group red 3 to 5 carbon atoms or, if A a methylene or ethylene group and / or one with e- "e alkanoyl group with 1 to 3 carbon-20 atoms or Mne alkoxycarbonyl group with a total of 2 to 4 carbon atoms substituted amino group, an ey-hydroxy, alklamino or dialkylamino group, each alkyl part containing 1 to 3 carbon atoms and each being substituted by a fnsnyI group, and / or 25 R2 a trif luc-methyl, cyan or Nitro group and / or R3 a fluorafcc and / or - 137 - t R4 an alkyl group with 1 to 3 carbon atoms and / or! R5 is an alkyl group with 1 to 4 carbon atoms, its cycloalkyl group with 3 to 6 carbon atoms, an al-kenyl group with 2 to 5 carbon atoms or a • 5 aralkyl group with 7 to 10 carbon atoms and / or Rg is a fluorine or chlorine atom, an alkylsulfanyl or Al u * ·; Kylsulfinylgruppe each with 1 to 3 carbon tonan representing a xthylene group or, when A represents the methylene group, 10 a group of the formula R9 0 I - CH - CH2 - in which represents an alkyl group having 1 to 3 carbon atoms, the optically active antipodes, the diastereomeric racemates and the optical antipodes and the acid addition salt 2. New phenylalkylamines of the general formula I according to claim 1, in which * R ^ is an amino group optionally substituted by a banzyl group or an alkoxycarbonyl group having a total of 2 to 4 carbon atoms, an alkylamine or dialkyl ^ aiüino group, each alkyl part 1 to 3 can contain carbon atoms, J R2 represents a hydrogen, chlorine, bromine or iodine atom, a trifluoromethyl, cyano or nitro group, Rg a fluorine, chlorine or bromine atom or a cyano group, · 25 a hydrogen atom or a methyl group, R5 is a hydrogen atom, an alkyl group with 1 to 3 carbon atoms, optionally substituted by a phenyl group, an allyl or cyclopropyl group, A is the methylene, ethylene or hydroxymathylene group and 30 B is a group of the formulas SU "" ... ...... '-' ί> 3 '- -' "-......” Ro 1 Rß ~ CH »(cH2) nDr y, · R7 ^ 'or - / Γ ~ ^ Τ R6 - s _ // y ^ vrrrry' '' ^., Whereby 0 7" kg, D and n as mentioned at the beginning are a hydrogen, fluorine or chlorine atom, a Kydroxy-, o Methcxy-, Sthoxy-, Eenzylcxy-, Kethylsulfsr.yl- or Me-5 thylsulfinylgruppe,: a hydrogen atom or a methoxy group or Eg and Ry together the methylenedioxy group and E is the n-propylene, 1-methyl-n-propylene, 1,1-dimethyl-n-propylene or n-butylene group or, if 10 A the methylene or ethylene group and / or one optionally by an esnzyl group or by an alkoxycarbonyl group with a total of 2 to 4 carbon atoms substituted amino, an alkylamino or dialkylamino group, each alkyl part containing 15 having 1 to 3 carbon atoms, and / or R2 having a trifluoromethyl, cyano or nitro group and / or Rg a fluorine atom and / or Rg is an alkyl group with 1 to 3 carbon atoms which is optionally substituted by a pbenyl group and contains 20 all represent yl or cyclopropyl group, also mean an ethylene group, sera optically active antipodes, their diastereomeric racemates and their optical antipodes and their physiologically tolerable acid addition salts with inorganic or organic acids. 'S .___________________________________ j ’· .......' .........'....." - 159 - 13. New phenylalkylamines according to claim 1, in! R-j is a sub- optionally substituted by a sthexycarbonyl group; substituted amino group, an alkylamino or dialkyl: amino group, each alkyl part having 1 to 3 carbon t 5; can contain atoms * -. I R2 is a hydrogen, chlorine or brenate or the cyano group, Rg is a fluorine or chlorine atom or the cyano group, "- - R ^ is a hydrogen atom or the methyl group, Rg is a hydrogen atom, an alkyl group optionally substituted by a phenyl-10 group 1 to 3 carbon atoms ('' atoms, the allyl or cyclopropyl group, IA the methylene or hydroxydethylene group and B a group of the formula i 'i - mean, where f * 7 I 15 E the n-propylene, 1 -Methyl-n-propylene, 1,1-dimethyl-n-propylene, n-butylene group or when (| I the ethoxycarbonylamino group and / or I: R2 the cyano group and / or! Rg a fluorine atom and / or | i 20 Rg is an optionally substituted by a phenyl group alkyl group having 1 to 3 carbon atoms, which represent - * allyl or cyclopropyl group, also an * ethylene group, Rg is a hydrogen atom, a hydroxyl or methoxy group 25 and J R7 is a hydrogen atom or Represent methoxy groups whose optically acti ve antipodes, their diastereomeric Race-J mate and their optical antipodes and their physiologically compatible I addition salts with inorganic or I 50 ^ organic acids. I / 1____. - 140 - -: ' 4. Ks'ûa phsnylalkylamines of the general formula I according to Än -spruch 1, in which is an amino, dimethylamino or alkylamino group with 1 to 3 carbon atoms in the alkyl part, 5 ^ 2 ene or bromine atom, a fluorine or chlorine atom or one of the radicals R2 or v - - Rj is also a cyano group, R ^ is a hydrogen atom or the methyl group, Rg is a hydrogen atom, an alkyl group with 1 to 3 carbon atoms 10 substance atoms or the allyl group, A the methylene or hydroxymethylene group 0 and 3 one in 3 positions by a phenyl, 4-hydroxyphysyl, 4-kethoxyphenyl or 4-chlorophenyl group substituted 15 n-propyl, 1-ksthyl-n-propyl or 1, IHDiinstkyi-n-propyl group, a 4- (4-kethaxyphenyl) butyl group or a 2- ( 3,4-Dimethoxy-phsnyl) ethyl group when Rg is an alkyl group with 1 to. 3 borrow carbon a, the allyl group and / or R2 shows the cyano group, mean 20; their optically active antipodes, diasterscsasse Race mate and their optical antipodes and their physiologically compatible acid addition salts with inorganic or organic acids. G '5. Today's phenylalkylamines of the general formula I were in contact with 1, in which%. to R, - and A are as defined in claim 4 and; B a in the 3-position by a phenyl, 4-hydroxyphenyl, 4-methoxyphenyl or 4-chlorophenyl group substituted "- n-propyl, 1-methyl-n-propyl or 1,1-dimethyl-n-propyl. Group or a 4- (4-methoxyphenyl) butyl group mean , their optically active .antipodes, their diastereomeric racemates and their optical antipodes and their physiologically compatible acid addition salts with inorganic or organic acids. 55 J 6 · 1- (4-amino-3,5-dichlorophenyl) -2- / N- (3-phenyl-propyl) -2-propylamine? -Ethanol, its optically active antipodes and their acid addition salts. --------------------------- ----------------------------_ -m _ ..... 7. 1- (4-Amino-3,5- dichlorophenyl) -2- ^ N- £ 1, 1 -dimethyl-3- (4-r-droxy-phenyl) -prcpyl / -ainino / -ethanol / its optically ak antipodes and their acid addition salts. 8. Medicament containing a compound according to claims 1-7 in addition to one or more inert Treger- and / or diluents. _SU Use of a compound according to claims 1-7: Manufacture of a medicament for combating Her :: r, t and circulatory diseases in a non-chemical way. O 10. Process for the preparation of new phenylalkylaraines of general formula R2 '/ 5 2 A - CH - N ·, (I) Γ · TR 3 O 1 - * V jf in the Rj one hydroxyl group, one optionally by a kanoyl group with 1 to 3 carbon atoms or ei :: alkoxycarbonyl group with a total of 2 to 4 carbon y atom-substituted amino group, an alkylamino- '-dialkylamino group, each alkyl part containing 1 to 3 atoms and each can be substituted by a phenyl, P * 2 and R3, which may be the same or different, Ec atoms, trifluoromethyl, cyan or Nitrc group or one of the radicals R2 or R3 also a hydrogenator. R4 represents a hydrogen atom or an alkyl group with 1 to carbon atoms, ——s. ........... .................- --------------------- ---------------------------, _ · τ / .2 _ -------------- Rc a hydrogen atom, a straight-chain or ver second alkyl group with 1 to 4 carbon atoms, a cyclo-alkyl group with 3 to 6 carbon atoms, an alkenyl! group with 2 to 5 carbon atoms or an aralkyl group with 5 to 7 carbon atoms, A the methylene, ethylene or hydroxymethylene group and: 3 a group of the formulas q -cH- (cH2) n-D ^^^ 6 R7 or; . R7 being 10 Rg is a hydrogen or halogen atom, a hydroxyl group, i '^ y is an alkoxy group which may be substituted by a phenyl group and has 1 to 3 carbon atoms, an alkyl-sulfenyl or alkylsulfinyl group each having 3 carbon atoms, 15 R ^ is a hydrogen atom, a hydroxyl group or an alkoxy group with 1 to 3 carbon atoms or Rg and R ^ zu-j sasmsn the methylenedioxy group, Rg is a hydrogen atom or an alkyl group with 1 to 3 carbon atoms, 20. an oxygen or sulfur atom, a sulfinyl - or Suifonylgruppe, n the number 1 or 2 and Λλ • \ - 1 A * 3; E optionally ait i by one or two alkyl groups; ’Each 1 to 3 carbon atoms substituted straight-chain alkyl group with 3 to 5 carbon atoms or, | i:: j if jl! 5: A is a methylene or ethylene group and / or I R \ j one by an alkanoyl group with 1 to 3 carbon; ^ atoms or an alkoxycarbonyl group with a total of j | ... 2 to 4 carbon atoms substituted amino group, l! - an Eydroxy, Alkyiamino or Dialkylamino group,: '| 10 where each alkyl part contain 1 to 3 carbon atoms j and each can be substituted by a phenyl group, and / or R_ a trifluoromethyl, cyano or nitro group and / or, S ^ l. a fluorine atom and / or j 15 an alkyl group having 1 to 3 carbon atoms and / | or]. Rj. An alkyl group with 1 to 4 carbon atoms, a | - ~ cycloalkyl group with 3 to 6 carbon atoms, a j * * alkenyl group with 2 to 5 carbon atoms or a -j ^ aralkyl group with 7 to 10 carbon atoms and / or | Rc represents a fluorine or chlorine atom, an alkylsulfenyl or Al- "O 3 kylsulfinyl group each having 1 to 3 carbon atoms j, an ethylene group or, if A represents the O methylene group, I 25 a group of the formula! . ii Γ- - - - CH - CH_ -, in which RQ represents an alkyl j δ y Λ group with 1 to 3 carbon atoms, and I their optically active antipodes, their diastereomeric racemates and their optical antipodes and their | 30 acid addition salts, characterized in that \ a) a compound of the general formula - 144 - / R5, pr R in which to R3 / R ,, and B are as defined above and X is a group of the formulas - CO - CH -, ' -. OH R, i i4 - CH - CH -, 0.Acyl - CH - CO -, o - CH2 - CO -, Z R. i I4 - CH - CH - or - ~ Z R. I i4 -: ^ - CH-CH2-CH ", where R ^ is like is defined, acyl is an organic acyl group and Z is a reductively cleavable group, is reduced or. n ’·% - 145 - b) a carbonyl compound of the general formula K - L, (III) in the 5. K together with an adjacent hydrogen atom in the alkyl part of the radical L denotes an oxygen atom, __ L that for B or, with the exception of the »gas atom atom, that for R ,. has the meanings mentioned at the outset or represents a gram of the formula r \ J h i - CH - A 'R 2 Y λ, where 10 T 1 · R 3 to R ^ are as defined in the introduction and A 'denotes the carbonyl, methylene or xylene group, or their A-aldehyde hydrate with an amine of the general formula 0 M Η - N, (IV) Q - J5 in which M and Q are different and have the meanings mentioned for 3 and Rq sin- - »or one of the radicals M or Q represents the group of the formula / 7 / / ....... - 146 - * Represents OC: _, where 3 .- bis and A are as defined at the beginning, and a reducing agent is reacted or Q c) one or more protective groups of a compound 5 of the general formula R, h V R2 ^ Y * ”- CH · - B ·, m vV R3 in the 0th and R ^ as defined at the beginning, R.j1 has the meanings mentioned for R ^ at the outset or represents a Hy-'IO; hydroxyl or amino group protected by a protective radical, An has the meanings mentioned for A at the beginning or has a Hy- "protected by a protective catch. droxymethylene group,. -, 1 which has 15 meanings mentioned at the outset or represents a protective radical for an amino group and B 'has the meanings mentioned for B at the outset or a group of the formulas / 1 _ 147 _ * R8 JT \ ^ V -CH- (CH2) nDr y Y or -BH ^ rR6 'o \ = tAR, 7 car, where * Rg, D, E and n are as defined at the beginning and R' and R „1, which can be the same or different, b 7 those for Rg and R ^ have the meanings mentioned at the outset or represent hydroxy groups protected by protective radicals, v? o at least one O of the radicals R ^ ', A ",' and / or B * must represent or contain one of the protective radicals mentioned above, are split off or. -jo 'd) a compound of the general formula R d ^ R Eal A - CH - N ___> iVI) TT / * 3 \ - 148 - in the Rj until Rjjf A and B are as defined above and Hai ein Represents chlorine, bromine or iodine atom, ent-5 is halogenated or e) a compound of the general formula • 4 VJ * 2 -. A - CH - N »V '3. I *:. in dar ·. '»' Rj bis and A are as defined at the outset, R5" which has the meanings mentioned above bs-10 or represents a hydrogen atom and B "has the meanings mentioned for B at the outset, where, if R, -" is not a hydrogen atom-f ^), at least one of the radicals R ^ or a hydroxy group or an amino group optionally substituted by a ^ 5 alkyl group having 1 to 3 carbon atoms, the alkyl group additionally being "may be substituted by a phenyl group, must represent, is alkylated or v ^ f) to produce a compound of the general. 20 Formula I, in which an amino group substituted by an alkanoyl group having 1 to 3 carbon atoms or an alkoxycarbonyl group having a total of 2 to 4 carbon atoms and R, - does not represent a hydrogen atom, is a compound of the general ^ 5 formula L g 9 '. .......... - -149 - ........: R4 ^ R „^ v ^^ a-CH-N? ’LTm>:; Tl * '· _ R3 in which R2 to R5, A and B are as defined above, with a compound of the general formula f Y - CO - R10, (ÏX) J rn üsr - R ^ Q. A hydrogen atom, a methyl or ethyl group or an alkyl group having 1 to 3 carbon atoms - and 'Y represents a nucleophilically exchangeable group, Ί0 is acylated or g) to prepare a compound of the general; O Formula I, in which D is a sulfinyl or sulfonyl group | represents a compound of the general formula i \ - Ri T3 r4 / 5 Rr A - CH - N ίΓ ^ \ TT ^ CH "(CVn 'S ° * A! ./VSR,, (X) \ cn / j .. ...... ..... - TscT ^ »in which Rg, A and n are as defined at the beginning and 'nt represents the number O or 1, is oxidized or jh) to produce a compound of the general formulas 5. nai i, in which D represents an oxygen or sulfur atom and Rg means no hydrogen atom, a compound of the general formula ~ '4 / R5 W a2 A "1 - CH - N,. | "" -CH- (CH) -V, (XI) II, 2 "R5" * * * in which R ^ to Rg, Rg and n are defined as above, 10. a nucleophilically exchangeable group and Ä "1 the methylene - or Xthylsngruppe mean, with a compound of the general formula O JTK ^ ': h - d «—ry, (XII)". R 7 in the R and R-, as defined in the introduction, and 15 D1 denotes an oxygen or sulfur atom , or whose alkali or alkaline earth metal salts are reacted / 1 Y ^ - Tpi - *% and, if desired, then a compound of general formula I obtained, which contains one, two or three optically active carbon atoms, in their optically active antipodes, their diastereomeric 5 racemates and whose optical antipodes are split up, and / or W a resulting compound of the general formula I r ~ is converted into its physiologically tolerable acid addition salts with inorganic or organic acids 10. o 11. The method according to claims 10a to 10d, 10g and 10h, characterized in that the reaction is carried out in a solvent. 12. The method according to claims 10a and 11, characterized geksnn- -J5 'characterized in that the reduction with a hydride, with aluminum isopropylate in the presence of a primary or secondary alcohol, with catalytically excited hydrogen or with nascent hydrogen is carried out. 13. The method according to claims 10a, 11 and 12, characterized Çy 20: indicates that the reaction at temperatures between -20 ° C and the boiling point of the reaction mixture, z.E. at temperatures between -20 ° and 100 ° C, is carried out. * 14. The method according to claims 10a and 11 to 13, characterized in that for the preparation of a compound of 25 general formula I, in which A represents the kydrosymethylene group:, the reduction with a complex metal hydride, with aluminum isopropylate, with catalytically excited water - substance or with nascent hydrogen. . 'U - *' “....... ....... ..............- 152 ~ - s * 15. The method according to claims 10a and 11 to 13, characterized; characterized in that for the preparation of a compound of the general formula I, in which A represents the methylene or ethylene 'group, the reduction with a complex metal-5; hydride such as sodium borohydride, sodium cyanoborohydride or; Lithium aluminum hydride or carried out with pyridine-Eoran V · “: is. 16. The method according to claims 10b and 11, characterized in that a complex metal hydride or catalytically excited hydrogen is used as the reducing agent. 17. The method according to claims 10b and 11, characterized in that formic acid is used as the reducing agent in the methylation. 18. The method according to claims 10b, 11 and 16, characterized ge-15 indicates that the reaction is carried out at temperatures between • -20 and 100 ° G. 19. The method according to claims 10b and 17, characterized in that the reaction is carried out at the boiling point of the reaction mixture. w 20. The method according to claims 10c and 11, characterized in that an acyl group used as a protective group. is split off hydrolytically with an acid or base. 21. The method according to claims 10c and 11, characterized gekenn- 7 w. records that a benzyl group "25 used as a protective group is split off hydrogenolytically. 22. The method according to claims 10d and 11, characterized in that the dehalogenation with triphenylphosphine, with hydrogen in the presence of a hydrogenation catalyst or with a complex metal hydride is carried out. Æ -, ___________________ _______________________________________________________ ......... - 153 - i! * 23. The method according to claims 10, 11 and 22, characterized in that the dehalogenation is carried out at temperatures between 0 and 150 ° c. 24. The method according to claim 10e, characterized in that 5. the alkylation of the nitrogen breath is carried out with a corresponding V 'alkyl halide or alkyl sulfate, with a corresponding carbonyl compound and a complex metal hydride or with formaldehyde / formic acid. 25. The method according to claim 10e, characterized in that •, .j 10 the alkylation of a phenolic hydroxyl group with an i corresponding alkyl halide, alkyl sulfate or diazoalkane is carried out. 26. The method according to claims 1Ce, 24 and 25, characterized σόι 5 that the reaction in the presence of a base and; 1.5 is carried out in a solvent. Ä 27. The method according to claims 10e and 24 to 26, characterized i characterized in that the reaction is carried out at temperatures between -10 and 50 ° C. 28. The method according to claim 10f, characterized in that the reaction in the presence of a base and in a gust! . ; is carried out. I * · j 29. The method according to claims 10f and 28, characterized- * - characterized in that the reaction is carried out at temperatures between O I i o L '> and 100 C. t ir- '; u * 30. The method according to claims 10g and 11, characterized in that the oxidation to produce a compound ί of the general formula I, in which D is the sulfinyl group I,. provides, with an equivalent of the Oxidaticnsmit-! is carried out. î! · /! ; ___________ / 0 ^ ______________________________________________ ____________ ....... ___________ <K à ___ ................. - 154 - 31. The method according to claims 10g and 11, characterized in that the oxidation for the preparation of a compound of general formula I, in which D represents the sulfonyl group, is carried out with an excess of the oxidizing agent used. ""; 32. Process according to claims 10g, 11, 30 and 31, characterized in that the oxidation is carried out at temperatures between -80 and 100 ° C. 33. The method according to claim 10h, characterized in that ^ 10 the reaction is carried out in the presence of an alkali base. 34. The method according to. Claims 10h and 33, characterized in that the reaction is carried out at temperatures between -10 • * and 100 ° C, but vorzucswaise at temperatures between 0 1 «15 and 50 ° c. V V; 35. Process according to claims 10h, 33 and 34, characterized in that the reaction is carried out in a solvent. O / n LKAXMh; »- / ^>" «v * Λ’ "· ν l