DE2536675A1 - NEW 3- (4-THIENO-OR-FURO SQUARE CLAMP ON 3.2-C SQUARE BRACKET FOR PYRIDINYLOXY) -2- PROPANOL DERIVATIVES, THEIR USE AND PRODUCTION - Google Patents

Description

Il alkyl with 3-7 carbon atoms or cycloalkyl with 3-7 carbon atoms / by alkyl with 1-4 carbon atoms rconosubstituiortes Cycloalkyl of 3-7 carbon atoms / cx -dlalkylpropynyl with 5-9 carbon atoms or α-dialkylallyl with 5-9 carbon atoms, Hydroxyalkyl with 2-7 carbon atoms or phenoxyalkyl with 8-11 carbon atoms, where in the last two radicals the oxygen atom is replaced by at least 2 carbon atoms is separated from the nitrogen atom to which R is bonded, means,

609811/0968

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R. for hydrogen or one in 2-, 3-, 6- or 7-position alkyl radical with 1-4 carbon atoms, for chlorine or bromine in the 2-, 3- or 7-position, one in 2- (or 3) position or in the 7-position NO or NHA radical, in which A is formyl or an alkanoyl group with 2-4 carbon atoms, or for one in the 2- or 3-position Permanent group of the series fluorine, cyano or COOB, in which B is alkyl with 1-4 carbon atoms means stands and

R _{2 represents} hydrogen or an alkyl radical in the 2-, 2-, 6- or 7-position. with 1-4 carbon atoms or for one in 2-, 3- or 7-

'. Position radical of the series chlorine or bromine or for an in 2- or 3-position fluorine atom,

and their acid additive.SGa.lze.
X preferably denotes sulfur.

R denotes in particular the phenoxyalkyl, α-dialkylpropinyl or alkyl group defined above; the latter two meanings are particularly preferred.

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253667b

If R stands for the alkyl or hydroxyalkyl radical defined above, so this preferred way is branched out, especially in the α-position to the nitrogen atom to which it is attached. Particularly preferred alkyl radicals cind isopropyl, tert-butyl, 3-pentyl and tert.Pentyl, Preferred Ilydroxyalkylreste are e.g. the a-Dimethylhydroxyäthyl- and oc-Dimethylhydroxypr-opy !group.

If R stands for the cycloalkyl radical defined above, it means in particular cyclopropyl, cyclopentyl or cyclohexyl.

R stands for that defined above, monosubstituted by alkyl Cycloalkyl group, its alkyl substituent is in particular methyl. One preferred alkylcycloalkyl group is 1-methylcyclohexyl.

R stands for α-dialkylpropynyl as defined above or α-dialkylallyl, so are those contained therein Alkyl groups are preferably identical and are in particular methyl.

If “R” stands for the “phenoxyalkyl radical” defined above, it means in particular phenoxyethyl.

R. preferably represents hydrogen, chlorine, bromine, cyano or the alkyl group defined above; the the latter two substituents are particularly preferred.

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R ₅ - preferably represents hydrogen or the above-defined alkyl group.

If R and / or R _{2 are} alkyl with 1-4 carbon atoms, these radicals contain in particular 1 or 2, preferably 1, carbon atom.

A preferably represents formyl or acetyl.

B preferably represents methyl, ethyl or tert-butyl.

R. is preferably in the 2- or 3-position, especially in the 2 position. R "is preferred in 7 position.

According to the invention, the new compounds of the formula I are obtained by

a) in compounds of the formula II in which X, R, R ₁

and R _{9 have the} above meaning and ** »*, _ ^ -

stands for a hydrolytically cleavable residue / the oxazolidine group is hydrolyzed or

b) Compounds of the formula III in which X, R. and R _{2 have the} above meaning and W is an anionic leaving group, substituted in the 4-position by reaction with compounds of the formula V in which R has the above meaning.

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The processes according to the invention can be carried out analogously to known methods.

Process a) is a hydrolysis of an oxazolidine » Oxazolidines are easily hydrolyzable (see Chemical Reviews 53. [1953] 315-317). In the connections of the formula II, Z and Z can therefore represent the remainder of any aliphatic or aromatic

matic aldehyde or ketone -T ^ C = O, with-

for example propionaldehyde, benzaldehyde, acetaldehyde, acetone. The hydrolysis the compounds of formula II is conveniently carried out under acidic conditions: as suitable acid is chosen, preferably dilute acid, in particular mineral acid, for example 0 / 5K to 3N hydrochloric acid or -IN sulfuric acid. You work in the presence of water. The use of a water-miscible, organic Solvent, such as a lower alkanol such as ethanol, is possible, but not necessary. The reaction temperature can vary, for example between 0 and about 80 °, it is expedient to work at an elevated temperature, for example at 60 to 80 °.

Process b) involves a substitution reaction on an aromatic nitrogen containing one Heterocycle which has an anionic on a carbon atom adjacent to the nitrogen Leaving group carries. W preferably means

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Chlorine, bromine or a lower alkylthio group such as methylthio; W in particular denotes chlorine. The substitution is easy, e.g. by Allowing a solution of a compound of formula III and a compound of formula V to stand. It is in an inert organic solvent under the reaction conditions, for example a lower alkanol such as tert-butanol

carried out. You work with

Advantageous in the presence of a base, for example an alkali metal alcoholate such as potassium tert-butoxide. The reaction temperature can vary between about 0 to about 80 °, it is convenient to work at room temperature. For the sake of acceleration the reaction can be stirred.

The compounds of the formula I can be used in free form as a base or in the form of addition salts present with acids.

Acid addition salts, for example the Hydrochloride or the kydrogen malonate, and vice versa.

The carbon atom in position 2 of the side chain of the compounds of formula I is asymmetric and these can therefore occur in the form of the corresponding enantiomers.

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zoobb / b

The enantiomers of the compounds of the formula I can be obtained in a manner known per se, ZlB. by performing the method of the invention using the corresponding enantiomers of the compounds of the formula II or V, the starting from (R) or. (S) -Glyceraldehyde can be obtained.

Some of the compounds of the formula III are known (F. Eloy and A. Deryckere, HeIv.CM m.Acta J53 [1S7O3, 645-647? F. Eloy and A. Deryckere, Bull.Soc.Chin. Beiges 79_ [1970 ], 301-312 and 407-414 and E. Bisagni et al. Bull. Soc. Chim. France [19743, 515-513).

The compounds of the formula IHa, wherein X and R

I.
have the above meaning, W chlorine or bromine

· "I
and R. for hydrogen or an alkyl group with 1-4 carbon atoms in the 2-, 3-, 6- or 7-position, a chlorine or bromine atom in the 2-, 3- or 7-position, a chlorine or bromine atom in the 7- Nitro group in position or a group in the 2- or 3-position of the series fluorine, cyano or COOB, in which B has the above meaning, is obtained, for example, by treating the compounds

öer formula IV, in which X, R, and R "have the above meaning own, with phosphorus oxychloride or phosphorus oxybromide.

Mononitration of compounds of the formula HIa in which X, R ₂ and W have the above meaning and R _{1 is} hydrogen, gives them the corresponding

60981 1/0968

corresponding 2- or 3-nitro derivatives. The position of the nitro group is not certain, presumably it is in the 2 position.

A 2 (3) - or 7-nitro group in the compounds of the formula III can be converted into an NHA group, a 4-chloro substituent can be converted into an alkylthic group.

The compounds of the formula IVa, wherein X is above Has meaning and R and R are hydrogen, an alkyl group in the 2-, 3-, 6- or 7-position with 1-4 carbon atoms or a group in the 2- or 3-position of the series fluorine, Means chlorine or bromine can be obtained by Curtius degradation via the vinyl isocyanates formed in situ - The corresponding 2-thienyl or 2 ~ furylacrylic acid azides obtain.

If desired, can then in the connections of the formula IVa by chlorination, eromination or nitration, a chlorine, bromine or nitro substituent inserted in 7-position and / or a bromine atom in the 2- or 3-position is substituted by a cyano group and this possible cyano group is converted into a COOB group by alcoholysis, where B has the above meaning owns, to be converted.

609811/0968

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These measures can be carried out analogously to known methods are in the literature and partly explained in the experimental part.

If the production of the starting products is not described, these are known or can be produced by processes known per se or analogously to those described here or analogously to processes known per se.

The compounds of the formula I are interesting in pharmacological testing Effects off and can therefore be used as a remedy.

These compounds regulate the circulation; so they show a blocking effect on the adrenergic ß-receptors. Due to this effect, the new substances can be used for prophylaxis and Therapy of coronary diseases used v / earth.

The compounds also exhibit an antiarrhythmic Effect on. Because of this effect, they are also used to treat cardiac arrhythmias suitable·.

The connections also show interesting ones Metabolic effects. Due to these metabolic effects, the substances can be used in conditions which leads to an undesired mobilization of free fatty acids due to psychological stress and glucose lead.

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253667b

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The compounds of the formula Iw in which R is a branched alkyl radical in the α-position to the nitrogen atom to which R is bonded and R _{1 is} hydrogen or a methyl radical in the 2- or 7-position or a in 2- or 3-position radical from the series is chlorine, bromine or cyano and rY stands for hydrogen or a methyl radical in the 7-position, and their acid addition salts.

The (S) -enantiomers of the compounds of formula I and their acid addition salts are pharmacological several times more active than the corresponding (R) -enantiomers. This is especially true for the (S) -1- tert -Butylamino-3- (2-methylthienot3,2-c] pyridin-4-yloxy) -2-propanol and its acid addition salts.

The invention also relates to medicaments which contain a compound of the formula I in free form or in Form of their physiologically acceptable addition salts with acids included. These remedies, for example a solution or a tablet, can be prepared by known methods, using the usual auxiliary and trihydric substances will.

In the following examples, all temperature data are given in degrees Celsius and are uncorrected.

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Example I;

(Procedure a)

2.0 g of 4- O-tert-butyl ^ -phenyl-S-oxazolidinyl methoxy) -2-methylthieno [3, 2-cJpyridine are heated to 70 ° for 1 hour in 20 ml of 1H hydrochloric acid, with Ether extracted and the aqueous phase made alkaline with solid potassium carbonate. It will extracted with ether, the Zietherlösung over Magnesium sulfate dried and concentrated (m.p. of hydrogen maleate 210-213 °).

The 4-nt.yl ^ -phenyl-S-oxazoridinylinethoxy used as starting material) -2-methylthieno [3,2-clpyridine is obtained from 2-formyl-5 methylthiophene in the following way:

According to Knoenenagel and Doebner, by reacting 2-formyl-5-methylthiophene-n with malonic acid 3- (5-Methylthieno-2-yl) acrylic acid obtained (melting point 163 ° to 165 °) is treated with thionyl chloride into the acid chloride and this by reaction with sodium azide in 3- (5-methylthieno-2-yl) acrylic acid azide convicted. Curtius degradation yields 4-hydroxy-2-niethylthieno [3,2-c] pyridine from Srnp. 214 to 216 ° (from methylene chloride). The latter gives 4-chloro-2-itiethylthieno [3,2-c3pyridine] by reaction with phosphorus oxychloride from m.p. 55 to 58 °. After reaction of this compound with 3-tert-butyl-2-phenyl-5-hydroxymethyloxazolidine in opposition

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Instead of potassium tert-butoxide, 4- (3-tert. Butyl-2-phenyl-5-oxazolidinyl methoxy) -2-methyl-thieno [3,2-c] pyridine as OeI.

Example 2;

grgganol
(Method b)

0.49 g of potassium are dissolved in 60 ml of tert-butanol when hot solved. After cooling, 1.5 g of l-tert-butylamino-2,3-dihydroxypropane are added and then

1.85 g of 4-chloro-2-methylthienot3,2-c] pyridine were added. After stirring for one day at room temperature, the mixture is heated to 50 ° for a further day. The reaction solution is concentrated in vacuo, the residue

taken up with IN hydrochloric acid and ether, the aqueous phase neutralized with 2N soda solution and extracted with methylene chloride. After drying over magnesium sulfate and concentration to give the title compound as an oil ■ that the hydrogen maleate-mp. 210 results with maleic acid in tetrahydrofuran to 213 °.

Analogous to Examples 1 and 2 and using of the corresponding starting compounds of the formula II, in which _ C! f for / ^ \\, -, ---

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is [method a)] or of the formula III / in which W stands for chlorine [method b)] the following is obtained Compounds of formula I:

609811/0968

OT CD CO

E.g.
No*. "X R. ^R l ^R 2 Salt form M.p. 3 S. tert-butyl 3-bromine _v 1 -methyl 171-172 ° 4th S. Isoprcpyl 2-methyl H 95-9 7 ° 5 S. tert-butyl 2 (3) nitro H 6th S. tert-butyl 2 (3) acetamido K '7 S. tert-butyl 3-cyano /-Methyl 161-163 ° A) δ S. tert-butyl 6-methyl K Em 148-151 ° 9 S. tert-butyl 7-ch.lor K Km 208-211 ° 10 S. tert-butyl 7-bromine H Em 206-208 ° 11 0 Isopropyl H H Hm 139-140 ° • 12 · - ■ s tert-butyl 2-fluoro H 13th S. tert-butyl 7-nitro H Ns ⁴ > 258-260 ° 14th S. tert-butyl 7-acetamido K

IV 2)

'Em = hydrogen maleate Fu - fumarate ■ Ks = naphthalene-1,5-disulfonate

3)

Kf = hydrogen fumarate

CO

E.g.
No. X R. ^R l ^R. ₂ Salt form Fu ² > M.p. 15th O Isopropyl 2-methyl H ■ 73-74 ° 16 S. α-dimethyl
propynyl K H 169-170 ° ■ 17 S. a-dimethyl
allyl H H HiTt 60981 1 18th
IS O
S. Isopropyl
α-dimethyl
propyi 6-methyl
H K
H Hm 73-75 ° / 0968 20th
21 co co Isopropyl
Isopropyl H
7-chlorine H
K Km 166-167 °
104-106 ° 22nd S. tert-butyl K K 196-198 ° 23 · O tert-butyl ■ H H NS 165-168 ° 24 S. tert-butyl 3-bromine 2-methyl. 25th S. tert-butyl 7-methyl H 208-211 °

Sn ~ hydrogen maleate '

Fu - fumarate

3)

Kf = hydrogen fumarate

Ns = naphthalene-1,5-disulfonate

CD

• cn

. E.g.
No. X R. ^R l ^R 2 Salζform Sr.?. B) 26th S. tert-butyl 2-erom K • Km 217-219 ° 27 S. tert-butyl 2-chlorine E. _Βί 3) 192-194 ° 28 S. tert-butyl 2-tert-butoxy
carbonyl W. Ns 239-241 ° A) 29 0 tert-butyl 2-methyl K Kf ·. 196-197 ° A) , 30 0 tert-butyl 7-chlorine K Hf 154-157 ° B) ■ 31 S. tert-butyl 2-cyano K Kir. 207-210 ° A) 32 S. tert-butyl 3-cyano 2-methyl B) 33 S. tert-butyl 2-carbathoxy K 34 S. Phenoxy- ¹
ethyl 2-cyano H 35 ■ 0 tert-butyl> 3-carbethoxy 2-methyl

2)

Hm = hydrogen maleate Fu

Ks ss naphthalene !, 5-disulfonate

Fumarate

Kf = Eydroge-ifusiarat

σ> ο co οο

E.g*
No. X R P ■■ "· ''
^R l ^R 2 Salt form M.p. A) 36 S. α-dimethylhy-
hydroxyethyl H K 37 S. 1-methylcyclo-
hexyl 2-cyano H 196-198 ° A) 38 S. Cyclopropyl H H 160-163 ° 39 S.
■ »■ · tert-butyl 3-cyano H Hm 40 S. tert-butyl 3-bromine H Hm

1) 4)

Km Ns

Hyärogenmaieinat

Fu = fumarate

³ ) Bf = hydrogen fumarate

• ~ naphthalene-i, 5 ~ disulfonate

ro

■ cn

CO

cn cd

cn

- 18 - 100-4211

A) The corresponding 4-hydroxy-2-carbonitrile or 4-hydroxy-3-carbonitrile derivative required as the starting compound of the formula IV can be obtained by using the 2-bromo or 3-bromo-4-hydroxy derivative of the Formula IV heated to reflux with CuCN in dimethylformamide / the solution concentrated under vacuum, in a warmed solution of potassium cyanide in H _? O poured and extracted after 1 hour at 50 ° with methylene chloride,

B) The corresponding 4-hydroxy-2-carboxylic acid ester required as the starting compound of the formula IV or 4-hydroxy-3-carboxylic acid ester can 'by boiling the corresponding 4-hydroxy-2 ~ carbon! trll- bsw. 4-Hydroxy ~ 3 ~ carbonitrile ~ Derivative of the formula IV under reflux in the corresponding alkanol and with the introduction of HCl gas can be obtained.

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Example 41;

groganol

The procedure is analogous to Example 1, starting from (S) -4- (3-tert-butyl-2-phenyl-5-oxazolidinylmethoxy) 2-methylthieno [3,2-c] pyridine (process a) or analogously to Example 2 , starting from 4-chloro-2-methylthieno [3,2-c] pyrldine and (S) ~ l-tert-butylamino-2,3-dlhydroxypropane (process b) and receives the title compound (melting point of the hydrogen maleate 166-167 °); t ^ on ^{6 =} " ¹² ' ² ° ^{(c = 1} Z ⁹⁴ ? methanol).

The starting products are obtained as follows;

a) 30 g of (R) -glyceraldehyde, 36 ml of tert-butylamine in 800 ml of ethanol are hydrogenated with H_ over 8 g of 10% Pd / C for 4 hours, the catalyst is filtered off and the solution is concentrated. From ethyl acetate / ether 2: 1, (S) -l-tert-butyl-'amino-2/3-dihydroxypropane is obtained in crystals with a melting point of 76 ° -81 °. M ₂ Q ~ "" ¹¹ ^ O ⁰ (c = 2, Of methanol).

b) 22 g of (S) -l-tert-butylamino-2,3-dihydroxypropane, 20.7 g of benzaldehyde and 46 ml of benzene are used Heated to reflux on a water separator for 16 hours. Benzene and benzaldehyde are distilled off and the residue is distilled in a high vacuum. The (S) -3-tert-butyl-5-hydroxy-

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253667b '

methyl-2-phenyloxazolidine falls as a yellowish oil ( _{boiling point n ηΐτηηι} 110-125 °); ₂ O = -17.8 ° (c = 1.99; chloroform).

c) 3 g of 4-chloro-2-methylthieno [3,2-C] PYrIdin and 3.8 g of (S) -3-tert-butyl-5-hydroxymethy1-2-phenyloxazolidine are added to a solution of 0.64 g Potassium introduced into 100 ml of tert-butyl alcohol and heated to reflux for 2 days. The solution is concentrated on a rotary evaporator and the (S) -4- (3-tert. Butyl-2-phenyl-5-oxazolidinylmethoxy) -2-methylthieno [3,2-c] pyridine obtained
processed directly.

Example 42;

The procedure is analogous to Example 1, starting from (R) -4- (3-tert-butyl-2-phenyl-5-oxazolidinylmethoxy) 2-methylthieno [3,2-c] pyridine (method a) or analogously to Example 2, starting from 4-chloro-2-methylthieno [3,2-c] pyridine and (R) -1-tert-butylamino-2,3-dihydroxypropane (method b) and receives the title compound (melting point of the hydrogen maleate 166-167 °); t «] ^« + 12.2 ° (c = 2.09; Methanol).

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The starting materials are described as in Example 41, starting from (S) -glyceraldehyde, obtained, the following intermediates being isolated:

a) (R) -1-tert-butylamino-2,3-dihydroxypropane

KAC

(M.p. 76-81 °)? M ^ O ^{= +14} '°° < ^{c = 2} ' ⁰² '> methanol).

b) (R) ^ -tert.Butyl-S-hydroxymethyl ^ -phenyloxazolidine (m.p. 110-125 °) j ^ OQ ^{6 A +17} °° (c = 2.0? chloroform).

c) (R) -4- O-tert-butyl ^ -phenyl-S-oxazolidinylv / methoxy) -2-methylthieno [3,2-c] pyridine (crude),

609811/096 8

ORIGINAL INSPECTED

100-4211

OH
I.

-CH -CH-CH -NHR

-Ri

-R. OH

ι

0-CH -CH-CH -NHR

609811/0968

Iv;

> -ClI, -CH

CH

■ X-

TI III

OH

r:

II Ig IV

OH

II

IVa

OH
I.

HO-CH-CH-CH-NHR

Claims (13)

- 23 - 100-4157 Patent claims: i. \ Process for the production of new 3- (4-thienc- or furo [3,2-c] pyridinyloxy) -2-propanol derivatives of formula I, wherein X stands for a sulfur or oxygen atom, R alkyl with 3-7 carbon atoms or cycloalkyl with 3-7 carbon atoms, through alkyl Hdt 1-4 carbon atoms n.onosubüLi: Cycloalkyl with 3-7 carbon atoms, a-diolkylpropinyl with 5-9 carbon atoms or a -Dialkylallyl u \ it 5-3 Kohloiistoffutoji.en, hydroxyalkyl with 2-7 Koh.l .;: istoffato-ion or phenoxyalkyl with 8-11 carbon atoms, whereby in the last two radicals the oxygen atom through at least 2 carbon atoms from the nitrogen atom the R is bound, is separated, means R _{1 stands} for hydrogen or an alkyl radical with 1-4 carbon atoms in the 2-, 3-, 6- or 7-position, for chlorine or bromine in the 2-, 3- or 7-position, one in the 2- (or 3 ) Position or in the 7-position NO ₂ - or NHA radical, in which A is formyl or an alkanoyl group with 2-4 carbon fator.fen, or for a group in the 2- or 3-position of the series fluorine, cyano or COOB, where B is alkyl having 1-4 carbon atoms and R _{2 represents} hydrogen or an alkyl radical in the 2-, 3-, 6- or 7-position with 1-4 carbons 609811/0968 - 24 - 100-4211 atoms or for one in the 2-, 3- or 7-position permanent remainder of the series chlorine or bromine or for one in the 2- or 3-position Fluorine atom, and their acid addition salts, characterized in that that he ti) in compounds of the formula II in which X, R, R. and R _{0 have the} above meaning and stands for a hydrolytically cleavable reate,. . the'-ox & solid group hydrolyzed or b} Compounds of the formula XII, above X, R, and R _{2 have the} above meaning and W denotes an anionic leaving group, by reaction *: with compounds of the formula V in which R has the above meaning, eubstituted in the 4-position and the compounds of the formula I obtained in this way as base or as acid addition salts. 2. Process according to Claim 1 for the preparation of l-tert-butylamino-3- (2-mefchyl ~ 4-thieno [3,2-c] pyridinyloxy) -2-propanol _/ · « ■ «ä _ * - .. - characterized in that one a) in a compound of the formula u in which X Sulfur, R, 2-methyl, R, hydrogen, R tert-butyl and -T ^ CiC. one hydrolytically The remainder can be split off, the oxazolidine group hydrolyzed · or 60981-1 / 0968 - 25 - 100-4211 b) a compound of the formula III / In der X sulfur, R. 2-methyl, R hydrogen and W is an anionic leaving group by reaction with 1-tert-butylamino-2 , 3-dihydroi :: ypropane, substituted in the 4-position. 3. The method according to claim 1 for the preparation of 1-tert-butylamino-3- (2-cyano-4-thieno [3,2-c] pyridinyloxy) -2-propano ^ - _: - - ■ __ marked / that man a) in a compound of formula II in which X is sulfur, R ₁ 2-cyano, R ₀ hydrogen, R tert-butyl and _! ^ CC a hydrolytic ν mean the removable radical, the oxazolidine group hydrolyzed - · ——— or b) a compound of the formula III in which . X is sulfur, R ^, 2-cyano, R _{2 is} hydrogen and W is an anionic leaving group, substituted in the 4-position by reaction with l-tert-butylamino-2,3-oil hydrojcypropane. 4. The method according to claim 1 for the preparation of l-tert-butylamino-3- (2-bromo-4-thieno [3,2-ci pyrldinylojcy «) -2-propanol, - * - - - -. -; r = .- ri - —- - characterized in that one a) in a compound of the formula II in which X is sulfur, R. 2-bromine, R _{0 is} hydrogen; R tert-butyl and -T> CC a hydrolytic 609811/0968 - 26 - 100-4211 detachable Rast mean the Oxazolldingruppe hydrolyzed or b) a compound of the formula III in which X is sulfur, R. 2-erom, R _{2 is} hydrogen and W is an anionic leaving group, substituted in the 4-position by reaction with 1-tert-butylaino-2,3-dihydroxypropane. 5. The method according to claim 1 for the preparation of the (S) -enantiomers of the compounds of formula I, in which X, R, R and R-, those specified in claim 1 Have meaning, characterized in that one %) in the (S) -enantiomers !! of the compounds of formula II in which X, R, R ₁ , R and Z- ^ _-0 ^ ^{1 2} ^ ' ^c - • have the meaning given in claim 1, hydrolyzing the Oxnzolidlngruppe or b) Compounds of the formula III in which X, R ,, R ₀ and W have the meaning given in claim 1, by reaction with the (5) * - en <* intiomers of the compounds of the formula V in which R is the in Claim 1 has the meaning given, substituted in the 4-position. 6. The method according to claim 5 for the preparation of (S) -l-tert.nutylamino-3- (2-m € thylthi © no [3,2-c) pyridin-4-yloxy) -2-propanol, marked by 60981 1/0968 - 27 - 100-4211 net, the π man a) in an (S) compound of the formula II in which X / R ₁ ι R-, ι R and Z- ^. ^ which in claim 2 I ^ - · have given meaning, hydrolyzed or the oxazolidine group b) a compound of the formula III in which X, R., R_ and W are those specified in claim 2 Have meaning by reacting with (S) -1-tert-butylamino-2,3-dihydroxypropane, substituted in the 4-position. 60981 1/0968 Deu tschlc.nd-Wsst - 28 - 100-4211 7. Compounds of the formula I in which X, R, R ₁ and .R have the meaning given in claim 1 own and their acid addition salts. 8. l ~ tert-butylamino ~ 3 ~ (2-ynethyl-4-thieno [3,2-c] pyridinyloxy) -2-propanol and its acid addition salts. 9 · L-tert-butylamino-3- (2-cyano ~ 4-thieno [3.2 ~ c3
pyridinyloxy) -2-propanol and its acid addition salts. 10. l-tert-butylamino-3- (2-bromo-4-thieno [3,2-c]
pyridinyloxy) -2-propanol and its acid addition salts. 11. The (S) -enantiomers of the compounds of the formula mel I, wherein X, R, R. and R ^ are those in claim 1 Have given meaning, and their acid addition salts. 12. (S) -l-tert-butylamino-3- (2-methyl-4-thieno
[3,2-c] pyridinyloxy) -2-propanol and its
Acid addition salts. 13. Remedies characterized in that they
Compounds of the formula I or their (S) -enantiomers or their physiologically tolerable ones
Contain acid addition salts. 3700 / VA / GB SANDOZ-PATENT GMBH 609811/0968