SU429584A3 - METHOD OF OBTAINING AMIPOLARTERED TERTIARY BUTANOLS - Google Patents

Description

The invention relates to a process for the preparation of new amino-substituted tertiary butanols, which have pharmacological activity and can be used in medicine. The proposed method, based on the known addition reaction of an organometallic, for example, organomagnesium compound on the carbonyl group of a ketone, produces tertiary butanols of the general formula I OH Hal-fJ C-CH. where Hal is chlorine, bromine; RI is hydrogen, chlorine, bromine; iR2 and iRa can be the same or different, unbranched or branched alkyl, alkenyl, dialkylaminoalkyl, cycloalkyl, phenyl, aralkyl or adamantyl radicals, with one of the R2 or Rs radicals being hydrogen or, together with nitrogen, forms a pyrrolidine ring, piperidrase, piperaserase, piperrase, pyperaserase, or pyrraserase, one of the radicals R2 or Rs. hexamethylenimine or camphidine, which may be substituted by hydroxy, alkoxy, phenyl or lower alkyl radicals; R4 is an unbranched or branched alkyl, cycloalkyl, cycloalkenyl, norbornyl, phenyl, aralkyl, naphthyl, pyridyl or thienyl radical, cycloalkyl radical substituted by hydroxy or lower alkyl groups, or a phenyl radical substituted by hydroxy, alkyl, alkalkyl, alkoxy or alkyl, substituted by hydroxy or alkyl, substituted by hydroxy or lower alkyl groups, or substituted by hydroxy or alkyl, substituted by hydroxy or lower alkyl groups, or substituted by hydroxy or alkyl, substituted by hydroxy or lower alkyl groups, or substituted by hydroxy or alkyl, substituted by hydroxy or lower alkyl groups, or substituted by hydroxy or alkyl, substituted by hydroxy or lower alkyl groups, or substituted by hydroxy, alkyl, cycloalkyl or substituted by hydroxy or lower alkyl groups, or substituted by hydroxy, alkyl, cycloalkyl TIO-, trifluoromethyl-, phenyl-, phenoxy groups and fluorine, chlorine or bromine, or their salts. For the synthesis of these compounds, a method is proposed according to which a compound of the general formula II Hal with -CHI, -CH, -C-CH.-CH-. H.N-y where RI-RS, Hal have the indicated meanings, is reacted with an organometallic compound of formula III

R4-X,

where R4 has the indicated meaning;

X is a metal atom of Group I or II of the Periodic System or a metal halide.

The process is carried out in the presence of a solvent, followed by isolation of the target product in a known manner as a base or salt. The exchange decomposition reaction is carried out, if necessary, under a protective gas in an inert solvent, for example ether, tetrahydrofuran or in a mixture of both, expediently at a temperature between -70 ° and + 65 ° C. In the reaction of exchange decomposition, an excess of an organometallic compound of the formula III is used, for example, from 2 to 10 times excess.

To obtain a compound of formula I, in which the radical R4 contains one or more hydroxyl groups, a compound of formula III is used, in which these groups are protected by easily removable protective radicals, for example trimethylsilyl, triphenylmethyl or tetrahydropyranyl groups. They are cleaved after an exchange decomposition reaction by conventional means, for example by hydrolysis.

In an exchange decomposition reaction, it may be advantageous in compounds of formula II to protect groups with active hydrogen atoms, for example hydroxy or amino groups, with an easily cleavable radical, for example a trimethylsilyl, triphenylmethyl or tetrahydropyranyl group. Thereafter, the protective group, if necessary, is separated by conventional means, for example by hydrolysis. It is, however, possible to carry out an exchange decomposition reaction without first introducing a protecting group.

The resulting compounds of formula I can be converted with inorganic or organic acids to their salts. Suitable acids were, for example, hydrochloric, hydrobromic, sulfuric acid, p-toluenesulfonic, phosphoric, lactic, citric, maleic, tartaric and oxalic acids. Example 1. 4-amino-3,5-dibromo-a-phenyl- (3- piperidinopropyl) -benzyl alcohol.

A solution of 211 g of bromobenzene (freshly distilled) in 500 ml of absolute tetrahydrofuran is slowly added dropwise while transferring to 32.7 g of magnesium in 100 ml of absolute tetragon of idrofuran. Then heated for half an hour under reflux, then cooled to room temperature. A solution of 54 g of 4-o-3,5-dibrom4-piperidino-butyrophenone in 500 ml of absolute tetrahydrofuran is added dropwise to the solution while moving. The mixture is then heated to boiling for 2 hours, cooled and a solution of ammonium chloride and ice is poured into the mixture. The organic phase is separated, the aqueous phase is extracted two more times with ether. The combined organic phases are sodium sulfate and evaporated under 5 vacuum. The solid brown residue is crystallized from 1/1 cyclohexane / absolute ethanol, and then from absolute ethanol. T. pl. 183-185 ° C.

Example 2. 4-Amino-a-cyclohexyl-3,5-di10 bromo-a- 3- (4-hydroxy-piperidino) propyl-benzyl alcohol.

In 6.4 g of magnesium in 20 ml of absolute tetrahydrofuran a solution of 42.5 g of cyclohexyl15 bromide (freshly distilled) in 150 ml of absolute tetrahydrofuran is slowly added dropwise with stirring. At the end of the addition, the mixture is heated under reflux for half an hour and then cooled to room temperature. A solution of 32 g of 4-amino-3,5-dibromo-4- (4-trimethylsilyloxypiperidino) butyrophenone in 200 ml of absolute tetrahydrofuran is then added dropwise with stirring. At the end of the addition, heat for 2 hours to

5 boiling point, cool and pour in a solution of ammonium chloride and ice. The organic phase is separated and the aqueous phase is extracted twice more with ether. The combined organic phases are dried with sulphate.

0 Sodium and evaporated under vacuum. The oily residue is purified by chromatography on a column of silica gel. The eluent is benzene, to which acetone is added. Then recrystallized two

5 times of isopropanol. T. pl. 161.5-163 ° C.

Example 3. 4-Amino-3,5-dibromo-a- (4-hydroxycyclohexyl )-- (3 - piperidino-propyl) - benzyl alcohol.

In 20.8 g of magnesium in 70 ml of absolute ether

While slowly stirring, a solution of 159 g of 4-chloro-trimethylsilyloxycyclohexane (freshly distilled) and 5.7 ml of ethyl bromide in 200 ml of absolute ether is added dropwise until the ether starts to boil slightly. At the end of the addition, the mixture is heated under reflux for 2 hours and then cooled to room temperature. To this, a solution of 68.5 g of 4-amino-3,5-dibromo-4-piperipo-dino-butyrophenone in 150 ml of absolute tetrahydrofuran is added dropwise with stirring. At the end of the addition, the mixture is heated under reflux for 2 hours, cooled and a solution of ammonium chloride and ice is poured into the mixture. The organic phase is separated and the aqueous phase extracted again with ether. The combined organic phases are evaporated under vacuum. The residue is triturated with 2 n. hydrochloric acid and insoluble solid is sucked off. Mother solution

washed with ether, alkalinized with caustic soda and extracted twice with ether. The combined ether phases are dissolved over sodium sulfate and evaporated in vacuo. The residue is purified by chromatography on a column of silica gel. Acetic acid, to which acetone is added, serves as eluent. It is then heated with ether and sucked off after cooling. Mp. 158-160 ° C.

Example 4. 4-Amino-3,5-dichloro-a-methyl-a (3-piperidino-propyl) -benzyl alcohol.

T. pl. 140-142 ° C.

Prepared from 4-amino-3,5-dichloro-4-piperidino-butyrophenone and methyl iodide as in Example 1.

Example 5. 4-Amino-3,5-dibromo-a-methyl-a (3-piperidino-propyl) -benzyl alcohol. square 159-160 ° C.

Obtained from 4-am "but-3,5-dibromo-4-piperino-butyrophenone and methyl iodide as in Example 1.

Example 6. 4-Amino-cc-ethyl-3,5-dibromo-cc (3-piperidino-propyl) benzyl alcohol.

T. pl. 123-125 ° C.

Prepared from 4-amino-3,5-dibromo-4-piperidino-butyrophenone and ethyl bromide analogously to example 1.

Example 7. 4-Amino-3,5-dibromo-a- (3-piperidino-propyl) -os-propyl-benzyl alcohol.

T. pl. 129-13GS.

Prepared from 4-amino-3,5-dibromo-4-piperidino-butyrophenone and propyl bromide analogously to example 1.

Example 8. 4-Amino-a-cyclohexyl-3,5-dibromo-a- (3 - piperidino-propyl) - benzyl alcohol.

T. pl. 121 - 124 ° C.

Prepared from 4-amino-3,5-dibromo-4-piperidino-butyrophenone and cyclohexyl bromide analogously to example 1.

Example 9. 4-Amino-a-cyclohexyl-3,5-dibromo-3- (3-hydroxy-piperidino) -propyl benzyl alcohol.

T. pl. 157-16GS.

Prepared from 4-amino-3,5-dibromo-4- (3-hydroxypiperidino) -butyrophenone and cyclohexyl bromide analogously to example 1.

Example 10. 4-Amino-Sb-cyclohexyl-3,5-dibromo-a- 3- (2-methyl-piperidino) propyl-benzyl alcohol.

Amorphous substance, structural evidence using IR, UV and NMR spectrum.

Prepared from 4-amino-3,5-dibromo-4- (2-methyl-piperidino) -butyrophenone and cyclohexyl bromide analogously to example 1.

Example 11. 4-Amino-a-cyclohexyl-3,5-dibromo-et-3- (3-methyl-piperidino) propyl-benzyl alcohol.

T. pl. 120 ° C (conversion of crystals); 137-139 ° C.

Prepared from 4-amino-3,5-dibromo-4- (3-methyl-piperidino) butyrophenone and cyclohexyl bromide in analogy to example 1.

Example 12. 4-Amino-a-cyclohexyl-3,5-dibrom-a-3- (4-methyl-piperidino) -propyl benzyl alcohol.

T. pl. 155-156 ° C.

Prepared from 4-amino-3,5-dibromo-4- (4-methyl-piperidino) butyrophenone and cyclohexyl bromide in analogy to example 1.

Example 13. 4-Amino-a-cyclopentyl-3,5-dibromo-a- (3-piperidino-propyl) benzyl alcohol.

T. pl. 141-142 ° C.

Prepared from 4-amino-3,5-dibromo-4-piperidino-butyrophenone and cyclopentyl bromide analogously to example 1.

T. pl. hydrochloride 139-14GS (decomposition).

Example 14. 4-Amino-a-cycloheptyl-3,5-dibrom-a- (3-piperidino-propyl) - benzyl alcohol.

T. pl. 138-140 ° C.

Prepared from 4-amino-3,5-dibromo-4-piperidino-butyrophenone and cycloheptyl bromide analogously to example 1.

Example 15. 4-Amino-a-cyclohexylmethyl3, 5-dibromo-a- (3-piperidino-propyl) is benzyl alcohol. T. pl. 150-153 ° C.

Prepared from 4-amino-3,5-dibromo-4-piperidino-butyrophenone and cyclohexyl methyl bromide in a manner similar to Example 1.

Example 16. 4-Amino-3,5-dibromo-a- (3-dimethylamino-propyl) - a- - phenyl-benzyl alcohol.

T. pl. 169-170 ° C.

Prepared from 4-amino-3,5-dibromo-4-dimethylamino-butyrophenone and bromo-benzene in analogy to example 1.

Example 17. 4-Amino-a- (4-chloro-phenyl) -3-, 5dibromo-a- (3-dimethylamino-propyl) -benzyl: ground alcohol.

T. pl. 126 ° C.

Prepared from 4-amino-3,5-dibromo-4-dimethylamino-butyrophenone and “.-Bromo-chloro-benzene in analogy to Example 1.

Example 18. 4-Amino-a- (4-chloro-phenyl) -3,5 dibromo- (3-piperidino-propyl) benzyl alcohol.

T. pl. 150.5-151.5 ° C.

Prepared from 4-amino-3,5-dibromo-4-piperidino-butyrophenone and “-bromo-chloro-benzene as in Example 1.

T. pl. hydrochloride 176-177 ° C (decomposition).

Example 19. 4-Amino-3,5-dibromo-a- (3-dimethylamino-propyl )-- (4-fluorophenyl) -benzyl alcohol. T. pl. 130-131 ° C.

Prepared from 4-amino-3,5-dibromo-4-dimethylamino-butyrophenone and m-bromo-fluoro-benzol as in Example 1.

PRI me R 20. 4-Amino-3,5-dibromo-a- (4-fluorophenyl) -a - (3-piperidino-propyl) is benzyl alcohol.

T. pl. 124.5-126 ° C.

Prepared from 4-amino-3,5-dibromo-4-piperidino-butyrophenone and / g-bromo-fluoro-benzene as in Example 1.

Example 21. 4-Amino-3,5-dibromo-c - (4-ft6phenyl) (4-hydroxy-piperidino) -propyl benzyl alcohol.

Amorphous substance, structural evidence using IR, UV and NMR spectrum.

Prepared from 4-amino-3,5-dibromo-4- (4-trimethylsiloxypiperidino) -butyrophenone and 4-bromo-fluoro-benzene as in Example 2.

Example 22. 4-Amnno-3,5-dibromo-a- (4-hydroxyphenyl) -a (3-piperidino-propyl) benzyl alcohol.

T. pl. 212-214 ° C.

Prepared from 4-amino-3,5-dibromo-4-piperidino-butyrophenone and 4-bromo-trimethylsilylphenol in analogy to example 3.

Example 23. 4-Amino-3,5-dibromo-a- (3-piperidino-propyl) -cc-4-tolyl-benzyl alcohol.

T. pl. 143-144 ° C.

Prepared from 4-amino-3,5-dibromo-4-piperidino-butyrophenone and 4-bromo-toluene in analogy to example 1.

Example 24. 4-Amino-3,5-dibromo-a- (3-piperidino-propyl) -ot- (4-a, a, a-trifluoro-tolyl) benzyl alcohol.

T. pl. 118-119 ° C.

, Obtained from 4-amino-3,5-dibromo-4-piperidino-butyrophenone and 4-bromo-a, a, a-trifluorotoluene analogously to example 1.

Example 25. 4-Amino-cc-benzyl-3.5-dibromo- (3-piperidino-propyl) -benzyl alcohol. m.p. 145.5-147.5 ° C.

Prepared from 4-amino-3,5-dibromo-4-piperidINO-butyrophenone and benzyl chloride in the same manner as in Example 1.

Example 26. 4-Amino-3,5-dibromo-a (3-piperid-ino-propyl )-- (2-pyridyl) -benzyl alcohol.

T. pl. 190-192 ° C.

Prepared from 4-amino-3,5-dibromo-4-pyperidino-butyrophenone and 2-bromo-pyridine in analogy to example 1.

Example 27. 4-Amino-3,5-dibromo-a-phenyl- (Z-piperidino-propyl) -benzyl alcohol.

In a mixture of 0.6 g of lithium and 30 cm of absolute ether, stirring, and under nitrogen protection, a solution of 6.28 g of bromobenzene and 40 cm of absolute ether is added dropwise. The mixture is then refluxed for 3 hours and then filtered with cotton wool. Under the same conditions, 4.04 g of 4-amino-3,5-dibrom-4-piperidino-butyrophenone in 120 cm of absolute ether is added dropwise to this solution for 20 minutes, then additionally boiled for another half hour. Ice and water are added to this mixture, the phases are separated and the aqueous layer is re-extracted with ether. The ether extracts are washed with water, dried over magnesium sulfate and evaporated in vacuo. The residue is crystallized by addition of isopropanol and the resulting crystals are recrystallized from ethanol. T. pl. 183-185 ° C.

Example 28. 4-Amino-3,5-dichloro-a- (3-dimethyl-amino-propyl) -a-phenyl-benzyl alcohol. , T. pl. 151 -151,5 ° C

Prepared from 4-amipo-3,5-dichloro-4-dimethylamino-butyrophenone and phenyllithi in a similar manner. 27.

Example 29. 4-Amino-3-bromo-5-chloro-a-pheny-l-a- (3-pyrrolidino-propyl) benzyl with irt. .

Mp, 187-189 ° C.

Prepared from 4-amino-3,5-chloro-4-nirrolidino-butyrophenone and phenyl lithium as in Example 27.

Example 30. 4-Amino-3,5-dibromo-a- (3-piperidino-propyl) - “-4-tolyl-benzyl alcohol.

T. pl. 143-144 ° C.

Prepared from 4-amino-3,5-dibromo-4-piperidino-butyrophenone and / 7-tolillity as in Example 27,

Example 31. 4-Amino-3,5-dibromo-a- (3-piperidino-propyl )-- (2-thienyl) -benzyl alcohol. T. pl. 176-178 ° C.

Prepared from 4-amino-3,5-dibromo-4-n-peridino-butyrophenone and a-thienyl lithium as in Example 27,

Example 32 4-Amino-3,5-dibromo-a- (2-methoxy-phenyl) -a- (3-piperidino-propyl) benzyl alcohol. T. pl. 139-141 ° C.

Prepared from 4-amino-3,5-dibromo-4-piperidino-butyrophenone and 2-methoxy-phenyl lithium as in Example 27.

Example 33 4-Amino-3-bromo-a-cyclohexyl-a-3- (4-hydroxy-piperidino) propyl-benzyl alcohol. T. pl. Ill -113 ° C.

Prepared from 4-amino-3-bromo-4- (4-trimethylsiloxy-piperidino) butyrophenone and cyclohexyl bromide in analogy to example 2.

Example 34. 4-Amino-3,5-dibromo-a- (4-hydroxy-cyclohexyl) - (4-hydroxy-piperidino) propyl-benzyl alcohol.

In 32 g of magnesium shavings in 100 ml of absolute ether slowly with stirring

a solution of 270 g of 4-trimethylsilyloxycyclohexyl chloride in 250 ml of absolute ether is added dropwise until the ether begins to boil slightly. After the addition, stir for 1 hour 30 minutes at a temperature of

return flow and then cooled to room temperature. While stirring, a solution consisting of 128.8 g of 4-amino3, 5-dibromo-4- (4-trimethylsilyloxypiperidino) -butyrofenone and 300 ml of absolute tetrahydrofuran is added dropwise. After the addition, the reflux temperature is heated for 2 hours, cooled and poured into a mixture of ice and ammonium chloride. The organic phase is isolated and extracted with dalcd ether. The combined organic phases are separated by shaking together with 2N. hydrochloric acid and then the aqueous phase is basified with concentrated ammonium and extracted with chloroform. The chloroform solution is dried with Na2SO4 and dried under vacuum to dryness. The solid residue is boiled once with ethanol, the undissolved components are filtered off in a still hot state and washed with ethanol.

T. pl. 227-229 ° C. Example 35 4-Amino-a-cyclohexyl-3,5-dichloro-a- (3-piperidino-propyl) benzyl alcohol. T. pl. 143-145 ° C. Made from 4-amino-3,5-dichloro-4-piperidino-butyrophenone and cyclohexyl bromide analogously to example 1. Example 36. 4-Amino-3-bromo-a-cyclohexyl-a- (3-piperidino-propyl) - benzyl alcohol . T. Il. 137-139 ° C. Made from 4-amino-3-bromo-4-piperidino-butyrophenone and cyclohexyl bromide in analogy to Example 1. Example 37. 4-Amino-3-bromo-a-cyclohexyl-a- (3-pyrrolidino-propyl) benzyl alcohol. T. pl. 153-155 ° C. Made from 4-amino-3-bromo-4-pyrrolidino-butyrophenone and cyclohexyl bromide as in Example 1. Example 38. 4-Amino-3-chloro-a-cyclohexyl-cc- (3-piperidino-propyl) benzyl alcohol. T. pl. 123-12b ° C. Made from 4-amino-3-chloro-4-piperidino-butyrophenone and cyclohexyl bromide in analogy to Example 1. Example 39. 4-Amino-3-chloro-a-cyclohexyl-a- (3-pyrrolidino-propyl) benzyl alcohol. T. pl. 144-146 ° C. Made from 4-amino-3-chloro-4-pyrrolidino-butyrophenone and cyclohexyl bromide analogously to example 1. Example 40. 4-Amino-bromo-5-chloro-a-cyclohexyl-a- (3-piperidino-propyl) - benzyl alcohol . T. pl. 137-139 ° C. Made from 4-amino-3-bromo-5-chloro-4-piperidino-butyrophenone and cyclohexyl bromide analogously to example 1. Example 41. 4-Amino-3-bromo-a-cyclohexyl-a- 3- (4-methyl-piperidino ) -propyl - benzyl alcohol. T. pl. 153-155 ° C. Made from 4-amino-3-bromo-4- (4-methylpiperidioio) -butyrophenone and cyclohexyl bromide analogously to example 1. Example 42. 4-Amino-3-bromo-a-cyclohexyl-a- (3-pyrrolidino-propyl) - benzyl alcohol. T. pl. 145-147 ° C. Made from 4-amino-3-bromo-4-pyrrolidino-butyrophenone and cyclohexyl bromide in analogy to Example 1. 10 Subject of the invention. Method for the preparation of amino-substituted tertiary butanols of general formula I Hal- | VC — CH —CH — CH — N R where Hal is chlorine, bromine; Ri is hydrogen, chlorine, bromine; Ra and Rs can be the same or different, unbranched or branched alkyl, alkenyl, dialkylaminoalkyl, cycloalkyl, phenyl, aralkyl or adamantyl radicals, with one of the radicals R2 and Ra being hydrogen or together with nitrogen form a pyrrolidine ring, piperidine, piperazine ring, hydrogen, or together with nitrogen form a pyrrolidine ring, piperidine, piperazine, hydrogen, or a hydrogen, or a nitrogen compound to form a pyrrolidine ring, piperidine, piperazine radical, hydrogen, or together with nitrogen form pyrrolidine, piperidine, piperazine radicals, hydrogen, or along with nitrogen form a pyrrolidine ring, piperidine, piperazine radicals, hydrogen, or hydrogen. hexamethylenimine or camphidine, which may be substituted by hydroxy, alkoxy, phenyl or lower alkyl radicals; R4 is a straight or branched alkyl, cycloalkyl, norbornyl, phenyl, aralkyl, naphthyl, pyridyl or thienyl radical, a cycloalkyl radical substituted by hydroxyl or lower alkyl radicals, or a phenyl radical substituted by hydroxy, alkyl, alkoxy, alkyl, alkyl, alkyl, alkyl, or alkyl, radicals, or a phenyl radical, substituted by hydroxy, alkyl, alkoxy, alkyl, alkyl, alkyl, or alkyl, radicals, or a phenyl radical, substituted by hydroxy, alkyl, alkoxy, alkyl, alkyl, alkyl, or alkyl, radicals, or a phenyl radical, substituted by hydroxy, alkyl, alkoxy, alkyl, alkyl, alkoxy, alkyl, or alkyl radicals, -, phenyl-, phenoxy-radicals and fluorine, chlorine or bromine, or their salts, characterized in that the compound of general formula II H01 is -C with -CHj-CH, -CHi-n.-C) where RI-Ra and Hal have the indicated meanings, are reacted with organometallic With a compound of formula III, R4 is X, where R4 is as defined; X is a metal atom of Group I and II of the Periodic System or a metal halide, in the presence of a solvent, and the active hydrogen atoms in the initial reagents are replaced with cleavable protective radicals, for example, trimethylsilyl, triphenylmethyl or tetrahydropyranyl, followed by cleavage of the protective groups and isolation of the target product B as base or salt in a known manner. Priority signs: 13.10.69 —Hal- chlorine, bromine; Ri is hydrogen, chlorine, bromine; R2 and Kz may be the same or different, unbranched or branched alkyl, alkenyl, dialkylaminoalkyl, cycloalkyl, phenyl, aralkyl or adamantyl radicals, with one of the R2 or Rs radicals being hydrogen or, together with nitrogen, form a pyrrolidine, piperidine, piperazine ring, or a nitrogen with piperidazine, hydrogen, or piperidazine, or hydrogen, together with nitrogen form a pyrrolidine ring, piperidrase, piperidazine, hydrogen or with nitrogen, they form a pyrrolidine, piperidine, pyperazine, or a hydrogen compound. hexamethylenimine or camphidine, which may be substituted by hydroxy or lower alkyl radicals; R4 is an unbranched or branched alkyl, cycloalkyl, norbornyl, phenyl, aralkyl, naphthyl, pyridyl or thienyl radical, cycloalkyl radical, substituted by hydroxyl or lower alkylene radicals or a phenyl radical, substituted by hydroxy, alkoxy, alkoxy or alkoxy radicals, substituted by hydroxy, alkoxy or alkoxy radicals, substituted by hydroxy, alkoxy or alkoxy radicals, substituted by hydroxy, alkoxy or alkoxy radicals, substituted by hydroxy, alkoxy or alkoxy radicals, substituted by hydroxy, alkoxy or alkoxy radicals, substituted by hydroxy, alkoxy or alkyloxy , phenyl, phenoxy radicals and fluorine, chlorine or bromine. 08.28.70 - R2 or Ra - together with nitrogen forms a ring of pyrrolidine, piperidine, piperazine, morpholine, hexamethylenimine or camphidine, which can be replaced by alkoxy or phenyl radicals.