DD210904A5 - PROCESS FOR PREPARING PYRIMIDINONES - Google Patents

Abstract

The invention relates to a process for the preparation of pyrimidinones for use as medicaments. The aim of the invention is the provision of compounds with antihypertensive, antiarrhythmic and beta-receptor blocking action. According to the invention, pyrimidinones of general formula I are prepared in which, for example: A and B, together with the two intervening carbon atoms, represent an optionally substituted phenyl ring or a pyridine ring, D an alkylene-o. Hydroxyalkylene group, R deep 3 u. R deep 5 each a hydrogen atom o. An alkyl group, R deep 4 is a hydrogen atom o. An alkoxy group u. R 6 is an alkyl group, an alkylene or hydroxyalkylene group which is terminally substituted by an optionally substituted phenyl or phenoxy group, and salts thereof.

Description

Berlin, 15.9.1983 AP C 07 D / 251 638/2 (62 352/18)

Process for the preparation of pyrimidinones Field of application of the invention

The invention relates to a process for the preparation of pyrimidinones and their Säadeaddltonasalzen.

The compounds prepared according to the invention have valuable pharmacological properties, in particular a hypotensive, antiarrhythmic and β-receptor-blocking action.

Characteristic of the known technical solution

In US Pat. No. 3,452,025, isoquinolin-1-ones are of the general formula

N-X-OH

in the

a thienyl group or a phenyl group optionally substituted by halogen atoms, amino, nitro, alkyl or alkoxy groups,

a hydrogen or halogen atom, an amino, nitro, alkyl or alkoxy group and

1äSER1933 * il7li5

-1- 15.9.1983

AP C 07 D / 251 638/2 (62 352/18)

X is a -CHR ₃ -CHR ₃ - or -CHR ₃ -CHR ₃ -CHR ₃ -GrUpPe, where R_ is a hydrogen atom, an alkyl group or a phenyl group optionally substituted by halogen atoms, amino, nitro, alkyl, or alkoxy groups, described which have antidepressant and tranquilizing properties »

Object of the invention

The aim of the invention is the provision of new compounds which are particularly suitable for the treatment of coronary diseases and hypertension »

Explanation of the nature of the invention

The invention has for its object to find new compounds with the desired properties and processes for their preparation.

The object has been achieved by finding the novel compounds of general formula I of the present application »

In EP-A-0.054.132, new pyrimidinones of the general formula

-1b- 15.9.1983

AP C 07 P / 251 638/2 (62 352/18)

0 - D -

^R 5

and their acid addition salts, in particular their physio-1ogisoh compatible acid addition salts with inorganic and organic acids, and processes for their preparation described Piese compounds have valuable pharmacological properties, in particular a hypotensive, antiarrhythmic and ß-receptor blocking effect ·

In the above general formula I mean

A and B together with the two intervening carbon atoms a pyridine ring or a phenyl ring which may be substituted by the radicals R ₁ and / or R ₂ , wherein

R _{1 is} a halogen atom, an amino or nitro groups an alkyl or alkoxy group each having 1 to 3 carbon atoms and

R is an alkoxy group having 1 to 3 carbon atoms, D is optionally substituted by a hydroxy group

Alkylene group having 3 or 4 carbon atoms, R ₃ and R ₅ , which may be the same or different, each one

Hydrogen atom or an alkyl group having 1 to 3 carbon atoms,

R _{4 is} a hydrogen atom or an alkoxy group having 1 to 3 carbon atoms and

R, a straight-chain or branched alkyl group with 1 to 6 o

Carbon atoms or a optionally substituted by a hydroxy group straight chain saturated alkylene group having 2 to 4 carbon atoms, which is terminally substituted by a phenyl or phenoxy group, wherein the phenyl nucleus in each case mono- or disubstituted by alkyl and / or alkoxy groups each having 1 to 3 carbon atoms - can. ^;: . = ··: ''. ' - ..,? '

For the in the definition of the radicals A, B, D, R ₃ , R ₄ , R ₅ and R, meanings mentioned above are, for example, for

IA and B together with the two intervening carbon atoms of the pyridine, phenyl, chlorophenyl, bromophenyl,

; Fluorophenyl, aminophenyl, nitrophenyl, methoxyphenyl, ethoxyphenyl, propoxyphenyl, isopropoxyphenyl, dimethoxy

'phenyl, diethoxyphenyl, methoxy-ethoxyphenyl, methoxypropoxyphenyl, xthoxy-isopropoxyphenyl, methoxy-e-chlorophenyl, ethoxy-bromophenyl or isopropoxy-fluorophenyl ring, for

ID that of the n-propylene, n-butylene, 2-hydroxy-n-propylene, 2-hydroxy-n-butylene or 3-hydroxy-ri-butylene group, for

R ₃ and R each represent a hydrogen atom, methyl, ethyl, propyl or isopropyl group, for

R ₄ represents a hydrogen atom, methoxy, ethoxy, propoxy or isopropoxy group, for

R _{6 is} methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, neopentyl, tert-pentyl, hexyl, 2-phenylethyl, 3-phenylpropyl , 4-phenylbutyl, 2-; Hydroxy-3-phenylpropyl, 2-hydroxy-4-phenylbutyl, 3-hydroxy-4-phenylbutyl, 2- (methoxyphenyl) -1-ethyl, 3- (methoxyphenyl) -propyl, 4- (methoxyphenyl) -butyl, 2-hydroxy-3- (methoxyphe- _L ny1) propyl, 2- (ethoxyphenyl) -äthyl-, 3- (isopropoxyphenyl) propyl, 2- (dimethoxyphenyl) -äthyl-, 3- ( Dimethoxyphenyl) propyl, 2-hydroxy-3- (dimethoxyphenyl) propyl, 2- (methylphenyl) ethyl, 2- (isopropylphenyl) ethyl, 3- (methylphenyl) propyl, 2-hydroxy 3- (methylphenyl) propyl, 4- (methylphenyl) butyl, 2- (dimethylphenyl) ethyl, 3- (dimethylphenyl) -. propyl, 2-hydroxy-3- (dimethy1phenyl) propyl, 2-phenoxy-f ethyl, 3-phenoxypropyl, 4-phenoxybutyl, 2-hydroxy-3-phenoxypropyl, 2-hydroxy-4-phenoxybutyl -, 3-hydroxy-4-phenoxy- \ butyl-, 2- (methoxyphenoxy) -äthyl-, 3- (methoxyphenoxy) propyl ^ 4- (methoxyphenoxy) -butyl, 2- (Äthoxyphenoxy) -äthyl-, 3- (Iso ι

! propoxyphenoxy) propyl, 2- (dimethoxyphenoxy) ethyl, 3- (di-methoxyphenoxy) propyl, 2-hydroxy-3- (dimethoxyphenoxy) propyl, 2-hydroxy-4- ( dimethoxyphenoxy) -butyl, 2- (methylphenyl ) -xyethyl, 2- (isopropylphenoxy) -ethyl, 3- (methylphenoxy) - ^; propyl, 2-hydroxy-3- (methylphenoxy) propyl, 4- (Methylphen- I oxy) -butyl, 2- (dimethylphenoxy) -äthyl-, 3- (dimethylphenoxy) - ^j propyl, 2-hydroxy -3- (dimethylphenoxy) -propyl, 2- (methyl-methoxyphenyl) -ethyl, 3- (methyl-methoxyphenyl-1) -propyl, 2-hydroxy-3- (methyl-methoxyphenyl) -propyl, 4 - (methyl ^{methacrylates;} oxyphenyl) -butyl, 2- (methyl-ethoxyphenyl) -äthyl-; 3- (ethyl | ethoxyphenyl) propyl, 2-hydroxy-3- (methyl-propoxyphenyl) propyl, 2- (methyl-methoxyphenoxy) -äthyl-, 3- (methyl-methoxy- \ phenoxy) -propyl , 2-hydroxy-3- (methylmethoxyphenoxy) -pro-

pyl-, 4- (methylmethoxyphenaxy) -butyl, 2- (isopropyl-roethoxy-.

phenoxy) -ethyl, 2-hydroxy-3- (methyl-isopropoxyphenoxy) -propyl or 2-hydroxy-3- (isopropyl-isopropoxyphenoxy) -propyl group.

However, preferred compounds of the above general formula I are those in which

A and B together with the two intervening carbon atoms, a pyridine ring or a phenyl ring which may be substituted by the radicals R. and / or R ₂ , wherein R _{1 represents} a chlorine atom, a methyl, methoxy or nitro group and

R _{2 represents} a methoxy group,

D is an n-propylene, n-butylene, 2-hydroxy-n-propylene, 2-hydroxy-n-butylene or 3-hydroxy-n-butylene group,

R ₃ and R ₅ , which may be identical or different, each represent an alkyl group having 1 to 3 carbon atoms or a hydrogen atom,

R. is a hydrogen atom or the methoxy group and

Rg is an alkyl group having 1 to 4 carbon atoms, an X-methyl group substituted at the 2-position by a methoxyphenyl, dimethoxyphenyl, methylphenoxy or methoxyphenoxy group, or a 2-hydroxypropyl group substituted at the 3-position by a methoxyphenoxy or methylphenoxy group, and their physiologically acceptable acid addition salts.

However, particularly preferred compounds of the above general formula I are those in which

A and B, together with the two intervening carbon atoms, form a phenyl, methoxyphenyl, dimethoxyphenyl or pyridine ring,

D is the n-propylene or 2-hydroxy-n-propylene group, R _{3 is} a hydrogen atom or the methyl group, R _{4 is} a hydrogen atom or the methoxy group,

a hydrogen atom or an alkyl group having 1 to 3 carbon atoms and

an alkyl group having 1 to 4 carbon atoms, an ethyl group substituted in 2-step by a methoxyphenyl, dimethoxyphenyl, methylphenoxy or methoxyphenoxy group, or a 2-hydroxypropyl group substituted in the 3-position by a methoxyphenoxy or methylphenoxy group, especially the compounds of the general formula

QH

0-CH ₂ -CH-CH ₂ -N

5, (Ia)

in the

R ₁ in the 6- or 8-position a methoxy group,

R _{2 is} a hydrogen atom or in 7-step a methoxy group and

R ₅ and Rg together with the intervening nitrogen atom, an isopropylamino, tert.butylamino, N-methyl-2- (3,4-dimethoxy-phenyl) -äthylamino-, 2- (2-Methoxypheny1) ethylamino, 2- (2-methylphenoxy) -äthylamino- or 2- (4-methoxyphenoxy) -äthylaminogruppe, and their physiologically acceptable acid addition salts with inorganic or organic acids.

It has now been found that the new compounds according to the invention can also be prepared by the following processes:

a) By reacting a Hydroxyphenylderivates of the general formula

0 ^:

(II)

in the

R ,, R, A and B are as defined above, with a compound of the general formula

X-D-

, (III)

in the

R ₅ , Rg and D are as defined above and X is a nucleophilically exchangeable group such as a halogen atom or

X together with a ß-hydrogen atom of the radical D represents an oxygen atom, wherein R _{5 represents} a protective group for an amino group and / or D may contain a protected by a protective hydroxy group »

The reaction is optionally carried out in a solvent, e.g. in ethanol, isopropanol, tetrahydrofuran, toluene, dimethylformamide or dimethyl sulfoxide, preferably in the presence of an acid-binding agent, e.g. an alcoholate or alkali metal carbonates such as potassium tert-butylate or potassium carbonate, and optionally in a pressure vessel at temperatures between 50 and 200 ° C, but preferably at temp.

temperatures between 70 and 150 ° C. However, the reaction can also be carried out without a solvent.

An acyl radical optionally used as a protective radical is subsequently hydrolytically in the presence of an acid or base, but preferably in the presence of a base such as sodium hydroxide solution. at temperatures up to the boiling point of the solvent or solvent mixture used

and an optionally used as a protecting group is then benzyl by hydrogenolysis ^, preferably be cleaved off using water ™ material in the presence of palladium / charcoal or platinum, at temperatures between 0 and 50 ° C.

b) dehydrogenation of a compound of the general formula

R 4

in the

R- to Rg, Ά, B and D are as defined above.

The dehydrogenation is carried out with a dehydrating agent such as sulfur, selenium dioxide, selenium, perbenzoic acid, copper-chromium: oxide, sodium borohydride, with a quinone such as o-chloranil, 1,4-benzoquinone or 2,3-dichloro-5,6-dicyan 1,4-benzoquinone, or a hydrogenation catalyst such as palladium, Raney nickel, nickel-cobalt or platinum in the melt or in a suitable solvent or solvent mixture such as Bensol, toluene, nitrobenzene, dimethylstilfoxide or tetrachloroethane

and depending on the dehydrating agent used, carried out at temperatures between 0 and 200 ° C. Thus, for example, the dehydrogenation with sulfur is preferably carried out in the melt at temperatures between 140-18O ⁰ C and with o-chloroanil at temperatures between 20 and 50 C.

If desired, the novel compounds obtained according to the invention can then be converted into their acid addition salts, in particular into their physiologically tolerated salts with inorganic and organic acids. Suitable acids are, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, lactic acid, citric acid, tartaric acid, oxalic acid or maleic acid.

The compounds of the general formulas II to IV used as starting materials are obtained by literature methods or are known from the literature. Thus, for example, a compound of the general formula II is obtained by reaction (see, for example, J. ehem. Soc. 1972, 709; DE-OS No. 2,114,884 and Syn. Comm. K), 241-243 (198O)) of a corresponding oxazine general formula

0 - COCH,

with a corresponding amine of the general formula

R ₃ - NH ₂ , (VI)

subsequent cleavage of the acetyl radical.

»9» 15.9.1983

AP C 07 D / 251 ... 639 / 2- (62 352/18)

A compound of general formula IV used as starting material is obtained, for example, by reacting a corresponding amide of the general formula

Il (VII)

with a corresponding aldehyde of the general formula

OHC - (J * Λ> \ _R (VIII)

in the presence of a base (see US Pat. No. 3,265,697).

"He mentioned at the beginning _f exhibit organ, the new compounds of general formula I and their physiologically acceptable acid addition salts with inorganic (and '' see acids have valuable pharmacological properties ₉ in particular a hypotensive, antiarrhytmlsche and ß-reaeptorenblockierende Viiirkung"

Ausfuhrungsbejspiel

The following examples are intended to explain the invention in more detail:

- 10 Example 1

2- [4- (2-hydroxy-3-tert-butylaminopropoxy) phenyl] 3 »This is 1-6-methoxy-3,4-dihydro-quinazolin-4-one

0.52 g (1.8 mmol) of 2- (4-hydroxyphenyl) -3-methyl-6-methoxy-3,4-dihydro-quinazolin-4-one are dissolved in 50 ml of ethanol with 2.2 ml of 2N sodium hydroxide solution ( 2 mmol + 10%) with 1.4 g (8 mmol) of 2-chloro-3-tert-butylamino-2-propanol (prepared analogously to M. Dubes et al., J. Med., JH, 328 (1971)). Boiled for 10 hours at reflux. It is then evaporated to dryness, the residue obtained is taken up in water and extracted by shaking with methylene chloride. The combined organic extracts are washed with 2N sodium hydroxide solution and with water, then dried over sodium sulfate and evaporated

 Yield: 210 mg (27.6% of theory), m.p .: 154-156 ° C (acetone)

^C 23 ^H 29 ^M 3 ° 4

Ber,: C 67.13 H 7.10 N 10.21 Fe.s 67.06 7.08 10.16

Example 2

2- $ ~ (2-hydroxy-3-tert-butylaminopropoxy) methoxy-3,4-dihydro-quinazolin-4-one

2.06 g (5 mmol) of 2- ^ 4- (2-hydroxy-3-tert-butylaminopropoxy) phenyl / 3-methyl-6-methoxy-1-2,3,4-tetrahydroquinazoline-4 »Are left on with 180 mg (5 mmol + 10%) of sulfur at 170 ° C for the reation. After 3 hours, the reaction is complete and the crude product obtained is purified over a silica gel column (particle size % 0.2-0.5 Hsn, eluent: methylene chloride / methanol 19s1 _f 9: 1). The colorless oil resulting after evaporation is crystallized from acetone.

- 11 -

Yield: 462 mg (23% of theory), m.p .: 158-160 ° C

^C 23 ^H 29 ^N 3 ° 4

Calc .: C 67.13 H 7.10 N 10.21

F .: 67.10 7.08 10.09

The following compounds are obtained analogously:

2- ^ 4- (3-diethylamino-propoxy) -phenyl7-3-methyl-3,4-dihydrochinazölin-4-one hydroiodide

2- ^ 4- (3-tert-butylamino-propoxy) -phenyl-7-8-methoxy-3,4-dihydro-quinazolin-4-one

Melting point of the dihydrochloride: 133-135 ° C

Melting point: 218-222 ° C

2- / J- (3-tert-butylamino-propoxy) -phenyl ^ -S-methyl-e, 7-dimethoxy-3,4-dihydro-quinazolin-4-one /

Melting point of the hydrochloride: 283-286 ° C

2- ^ 4- (2-hydroxy-3-tert-butylaminopropoxy) -phenyi7-3-methyl-6-nitro-3,4-dihydro-quinazolin-4-one Melting point: 267-27O ⁰ C (acetone / ether)

2- [A- [A- (2-Hydroxy-3- (4-methoxyphenoxy) -propylamino) butoxy] - (phenyl) -3-methyl-6-methoxy-3,4-dihydro-quinazolih-4-one Melting point of the hydrochloride: 1O5-1O7 ° C

2-O-4-2-Hydroxy-3- (2- (3,4-dimethoxyphenyl) -N-methyl-ethylamino) -propoxy-7- ^r- phenyl-3-methyl-6-methoxy-3,4-dihydro-quinazoline ~ 4-on melting point of dihydrochloride: 152-155 ° C

- 12 -

2-4 ° C ~ 3- (2-hydroxy-3- (4-methoxyphenoxy) -propyl! Amino) -; |. phenyl 3-methyl-6-methoxy-3,4-dihydro-quinazolin-4-one m.p. 134-136 ° C

2- ^ M ~ (2-hydroxy-3-tert-butylamino-propoxy) 3,4-dihydro-quinazolin-4-one m.p .: 189-191 ° C

; 2-A / 2-hydroxy-3- · (2- (2-methoxyphenyl) amino -Mthy!) -Propox ^ / - phenyl / -3-methyl-6-methoxy-3, 4-dihydro-quinazolin-4 -on melting point of dihydrochloride: 156-158 ° C

2- {J- (2-Hydroxy-3-diethylamino-propoxy) -phenyl-3-methyl-6-methoxy-3,4-dihydro-quinazolin-4-one Melting point: 123-125 ° C (acetone / Ether)

2- [I- (2-hydroxy-3-isopropylamino-propoxy) -phenyiy-S-methyl-6-methoxy-3, 4-dihydro-quinazolin-4-one Melting point: 13O-132 ° C

2-M- (2-hydroxy-3-isopropylamino-propoxy), 3,4-dihydro-quinazolin-4-one m.p .: 198-2O1 ° C

2-J-2-Hydroxy "3- (2- (2-methoxyphenyl) -ethylamino) -phenyl / 3-methyl-8-methoxy-3,4-dihydroquinazoline-4" "on melting point of the dihydrochloride : 12o-123oC

2- ^ 4- (2-Hydroxy-3-diethylamino-propoxy) methoxy-3,4-dihydro-quinazolin-4-one Melting point of dihydrochloride: 127-130 ° C

- 13 -.

² "* 4- (2-Hydroxy-3- (2- (2-methylphenoxy) -ethylamino) -propoxy-phenyl-3-methyl-8-methoxy-3,4-dihydro-quinazolin-4-one melting point of the hydrochlorides : 122-125 ° C

2- / 4- / 3- (2-hydroxy-3- (3-methylphenoxy) -propylamino) -propoxy / -phenyi-3-methyl-8-raethoxy-3,4-dihydro-quinazolin-4- on melting point: 138-140 ° C

2- £ £ 4- 2-hydroxy-3- (2- (2-methoxyphenyl) -äthylamino) propoxy ^ - phenyl ^ -3-methyl-6, 7-dimethoxy-3,4-dihydro-quinazolin-4 -on melting point of trihydrochloride: 188-192 ° C

2- ^ 4- £ 2-hydroxy-3- (2- (2-methylphenoxy) -äthylamino) propoxy / -phenyf? -3-methy1-6,7-dimethoxy-3,4-dihydro-quinazolin-4- Melting point: 195-198 ° C

2- ^ 4- ^ 3- (2-hydroxy-3- (3-methylphenoxy) -propylamino) -propoxy- phenyne Ϊ? -3-methy1-6, 7-dimethoxy-3,4-dihydro-quinazolin-4-one Melting point of the hydrochloride: 222 C

2- / 1-Methoxy-4- (2-hydroxy-3-tert-butylaminopropoxy) phenyl / 3-methyl-6-methoxy-3,4-dihydro-quinazolin-4-one Melting point: 10-2-150 ° C (acetone / ether)

2- / 4- (2-hydroxy-3-tert-butylaminopropoxy) -phenyl-7,3,6-dimethyl-3,4-dihydroquinazolin-4-one m.p .: 146-15 ° C (acetone / ether)

2- / 4- (2-hydroxy-3-isopropylaminopropoxy) phenyl [7-3.6-dimethyl-3,4-dihydro-quinazolin-4-one

Melting point: 15O-153 ° C (acetone / ether)

? 2 - / - (2-hydroxy-3-tert.butylaminopropoxy) phenyl / -3-methyl-6-chloro-3,4-dihydro-quinazolin-4-one Melting point: 166-168 ⁰ C (acetone / ether )

- 14 -

2-Z3 "(2-hydroxy-3-isopropylamino-propoxy) -phenyl17-3-methyl-3,4-dihydro-pyrido-2,3-e-pyrimidin-4-one melting point of the dihydrochloride 142-145 ° C

2- / 4- (2-hydroxy-3-tert-butylamino-propoxy) "phenyjL / -3-methyl-3,4-dlhydro-pyrido / 2.3 to 7

Melting point of the dihydrochloride: 168-171 ⁰ C.

2- / 4- / 2-hydroxy-3- (2- (4-methoxy-phenoxy) -ethyl) -propoxy-JT-phenyl-3-methyl-3,4-dihydro-pyrido / p, 3-je / pyrimidin-4-one melting point 132-135 ° C

2 - / 4- (2-hydroxy-3-isopropylamino-propoxy) phenyl / -3-methyl-3 _f · 4- dihydro-pyrido / 3,4-e7pyrimidin-4-one Melting point of the dihydrochloride: 122-125 ° C

2- / 4- (2-hydroxy-3-tert-butylamino-propoxy) -phenyl ^ / - 3-methyl-3,4-dihydro-pyrido / 3,4-e / pyrimidin-4-one melting point of the dihydrochloride: 171-173 ° C

2 - ^ - / 5- (2-hydroxy-3- (4-methoxyphenoxy) propylamino) -propoxy-phenyl-8-methoxy-3,4-dihydro-quinazolin-4-one melting point of the dihydrochloride: 19O- 193 ° C

2- / 4- (2-hydroxy-3-tert-butylamino-propoxy) -phenyl! / - 3-isopropyl-6-methoxy-3,4-dihydro-quinazolin-4-one m.p .: 145-147 ° C

2- / 4-hydroxy-3- (2- (3,4-dimethoxyphenyl) -N-propyl-ethyl) -propoxy -phenyl-S-methyl-e-methoxy-S-dihydro- quinazolin-4-one melting range: 112-117 ° C.

Claims (4)

-15- 15.9.1983 AP C 07 D / 251 638/2 (62 352/18)  arfindunpsanspruch 1. Process for the preparation of pyrimidones of general (DV in the A and B together with the two intervening carbon atoms a pyridine ring or a phenyl ring which may be substituted by the radicals R ₁ and / or Rp, wherein R _{1 is} a halogen atom, an amino or nitro group, an alkyl or alkoxy group each having 1 to 3 carbon atoms and R _{2 represents} an alkoxy group having 1 to 3 carbon atoms, D is an optionally substituted by a hydroxy group alkylene group having 3 or 4 carbon atoms, R.sup.J and R.sup.1, which may be the same or different, each represents a hydrogen atom or an alkyl group having 1 to 3 carbon atoms, Rq is a hydrogen atom or an alkoxy group having 1 to 3 carbon atoms and Rg is a straight-chain or branched alkyl group having 1 to 6 carbon atoms or a straight-chain saturated alkylene group having 2 to 4 carbon atoms which is optionally substituted by a hydroxy group and which -16- 15.9.1963 AP O 07 D / 251 638/2 (62 352/18) is constantly substituted by a phenyl or phenoxy group, wherein the phenyl nucleus may be mono- or disubstituted by alkyl and / or alkoxy groups each having 1 to 3 carbon atoms, mean, and of their acid addition salts gekennaeiohnet characterized in that a) a hydroxyphenyl derivative of the general formula 0!
A OH (ID, in the R-, R-, A and B are as defined above, with a compound of the general formula X-D-N "^^ (III), in the Rc »Rg and D are as defined above and X represents a nucleophilically exchangeable group or X together with a ß-hydrogen atom of the radical D represents an oxygen atom, wherein R _n .  5 represents a protective group for a mino group and / or D may contain a hydroxyl group protected by a protective group, and, if appropriate, subsequently a protecting group used is split off, or b) a compound of the general formula in the -17- 09/15/1983 AP G 07 D / 251 638/2 (62 352/18) -X) -N, R, to R
is hydrogenated A, B and D are as defined above, de and, if desired, subsequently converting a compound of general formula I obtained into its acid addition salt, in particular with a physiologically tolerated inorganic or organic acid * Process according to item 1, characterized in that the reaction is carried out in a solvent. 3. Process according to points 1a and 2, characterized in that the reaction is carried out in the presence of an acid-binding agent · 4. The method according to points 1a, 2 and 3, characterized in that the reaction is, however, carried out at temperatures between 50 and 200 ⁰ O, preferably at temperatures between 70 and 150 ⁰ C · Process according to point 1b and 2, characterized in that the dehydrogenation is carried out at temperatures between 0 and 200 ^° C.