Quinazoline derivatives, process for their preparation, pharmaceutical preparations and their preparation.

Preferred compounds of formula I are:

D-6-chloro-1,5-dihydro-3-methylimidazo [2,1b] quinazolin-2 (3H) -one,

D1,5-dihydro-3,6-dimethylimidazo [2,1-b7]^kinazolin2 (3H) -one,

D-7-bromo-1,5-dihydro-3-methylimidazo [2,1-b] quinazolin-2 (3H) -one, and their salts.

Examples of compounds of formula I are:

L-6-chloro-1,5-dihydro-3-hydroxymethylimidazo [2,1-b] quinazolin-2 (3H) -one,

L-6-chloro-1,5-dihydro-3-phenylimidazo [2,1-b] quinazolin-2 (3H) -one,

L-6-chloro-1,5-dihydro-3-isobutylimidazo [2,1-b] quinazolin-2 (3H) -one,

L-3-Benzyl-6-chloro-1,5-dihydro-imidazo [2,1-b] quinazoline-2 (3H) -one, and their salts.

The new compounds may exist in different tautomeric forms. The group of compounds of formula I also comprises tautomers, e.g. those of formula

<img file="FI63409B_D0001.tif" />

Compounds of formula I and their tautomers, e.g.

Ia and Ib may further exist as racemates or in optically active form.

Examples of physiologically acceptable salts include mineral acid salts such as hydrochlorides, hydrobromides, sulfates and phosphates; salts of organic sulfonic acids such as alkyl sulfates and aryl sulfonates; and carboxylic acid salts such as succinates, citrates, tartrates and maleates.

The imidazoquinazolinones of the formula I differ from the known compounds described in DE-A-2 257 376, 2 319 851 and 2 402 454 in that in known compounds the keto group is in the 5-position, whereas in the compounds now described it is in the 2-position. The new imidazo [2,1-b] quinazolin-2 (3H) -ones also differ in FI publication 56 012 (corresponding to DE 2 305 575) and in J. Med. Chem. 18, 1975, 225 and U.S. Patent Nos. 3,983,119, 3,983,120 and 3,988,340, in that, in contrast to known compounds, the new compounds are substituted in the 3-position. In addition, the compounds of the formula I have a considerably better effect than the known compounds. The new compounds cause a substantially smaller increase in heart rate (lower tachycardia) than the known compounds, while the positive effect on muscle contraction (inotropic effect) is of the same order of magnitude as the new and known compounds. The advantageous properties of the compounds of the formula I over the known compounds are shown in Table II below.

The compounds of formula I and their tautomers, D- and L-forms and salts can be prepared by:

(a) a compound of formula

R .NH

II

<img file="FI63409B_D0002.tif" />

4 wherein R to R are as defined above and R is C₄- alkyl is reacted with bromocyanine, or

(b) a compound of formula

<img file="FI63409B_D0003.tif" />

4 wherein R - R are as defined above, is treated with ammonia

The reaction of a compound of formula II with bromocyanine is conveniently carried out under heating in a solvent such as a lower alcohol, e.g. ethanol. The reaction of a compound of formula III with ammonia is conveniently carried out under heating in a solvent such as a lower alcohol, e.g. ethanol, and water.

2

The compound of the formula I in which R and / or R is hydrogen can be halogenated in a manner known per se. Thus, for example, a solution of a 6-, 7-, 8- and 9-unsubstituted compound can be reacted with bromine in acetic acid to give a 7-bromo compound.

Compounds of formula I may be prepared according to Reaction Scheme I wherein Y is chlorine or bromine and R, R and 3

R has the same meaning as above.

Compounds of formula I may be further prepared according to Reaction Scheme II, wherein Z is oxygen or sulfur, M is ammonium, potassium or sodium and other symbols have the same meaning as above.

Reaction Scheme I ^:B2^NH2

B₂/ Pt, Pd or Raney nickel

-&gt;

e.g., C₂In HgOH • NH.

'ch₂nh₂

BrCN e.g. C ~ H_rIn OH

<img file="FI63409B_D0004.tif" />

Y-CH-COY l₃

R

O 6esim. in tetrahydrofuran 0-100 ° C

M /

Reaction Scheme II

<img file="FI63409B_D0005.tif" />

MZ-CN acetic acid or pyridine

25-100 ° C ch₃i / k₂c/o₃THF, 20-100 ° C

<img file="FI63409B_D0006.tif" />

R¹

R²

WELL,

5CH₃

<img file="FI63409B_D0007.tif" />

i ^ / Pt, Pd / or Raney nickel e.g. C₂B₃At 0H

<img file="FI63409B_D0008.tif" />

<img file="FI63409B_D0009.tif" />

nissa

NH 4 C₂H (-QH or pyridii ·

20-100 ° C, 1-50 atm.

R¹

R²

<img file="FI63409B_D0010.tif" />

The compounds of formula II are new.

The starting compounds of formulas II and III can be prepared according to Reaction Scheme III, wherein X is halogen and the other symbols are as defined above, or as described in the Examples, respectively.

Ί

Reaction Scheme III

<img file="FI63409B_D0011.tif" />

<img file="FI63409B_D0012.tif" />

B₂NCHCOOR⁴

CICHCOOR

<img file="FI63409B_D0013.tif" />

<img file="FI63409B_D0014.tif" />

<img file="FI63409B_D0015.tif" />

<img file="FI63409B_D0016.tif" />

The compounds of the formula I, their tautomers and the physiologically tolerable salts of such compounds can be used as medicaments. For example, they inhibit platelet aggregation and can therefore be used to prevent the formation of thrombosis. In addition, they affect blood circulation. Thus, due to their positive (inotropic) effect on muscle contraction, they can be used to treat and prevent heart failure and heart failure without causing substantial tachycardia.

The compounds of the formula I and their tautomers can be used as medicaments, for example as pharmaceutical preparations containing them or their salts in admixture with pharmaceutical, organic or inorganic inert carriers suitable for enteral, percutaneous or parenteral administration, such as water, gelatin, acacia, lactose. , with starch, magnesium stearate, talc, vegetable oils, polyalkylene glycols, petrolatum, etc. The pharmaceutical preparations may be in solid form, e.g. tablets, granules, suppositories, capsules; in semi-solid form, e.g. as ointments; or in liquid form, e.g. as solutions, suspensions or emulsions. They may be sterilized and / or contain excipients such as preservatives, stabilizers, wetting agents! emulsifiers, salts for varying the osmotic pressure or buffers. They may additionally contain other therapeutically valuable substances. Oral administration of the compounds of the invention is preferred. In adults, a daily oral dose of 0.5 to 30 mg / kg and a parenteral dose of 0.05 to 10 mg / kg are contemplated.

The anti-aggregation effect was demonstrated using the method of BORN / Nature 194, 927 (1962} J and MICHAL and BORN / Nature 231, 220 (1971) ./ The aggregation rate was taken as the experimental parameter and the effective concentration (EC q) was obtained from dose-response curves.

Human plasma was obtained from intravenous blood digested with citrate (10.6 mM) by centrifugation. To 0.18 ml of plasma was added 10 of an aqueous suspension of the test compound, incubated for 10 min. At 37 ° C, after which aggregation was initiated by the addition of 10 μl of collagen tetril suspension.

Rabbit plasma was obtained by citration (9 mM) from digested arterial blood by centrifugation. To 1 ml of plasma was added 10 μl of test solution and incubated for 1 min. At 37 ° C, followed by the addition of 8 2 μl of collagen fibril suspension or 10 adenosine diphosphate (ADP) 10⁴ M in saline. Plasma incubated with dimethyl sulfoxide was used as a control.

The results are reported in Table I.

The positive inotropic effect was measured in awake German Shepherds after oral administration of the test substance. The animals are fitted with a pressure-telemetry system for this purpose, with the pressure sensor attached to the left ventricle. The pressure in the left ventricle is obtained through a radio transmitter mounted on the animal and is received by a suitable antenna and reception system, demodulated and amplified. By differentiating the ascending curve describing the left ventricular pressure (LVP), the maximum pressure rise rate (dLVP / dt) is calculated._mak_S) · Considered as a parameter of contractility. At the same time, the heart rate is plotted through a cardiotachograph. The effect on muscle contraction is reported in dLVP / dt_ma^_sas a percentage change in (Δ%) and duration of action in minutes (min.). Tachycardia is expressed as the percentage change in heart rate (Δ%) after administration of the test substance and the duration of action is reported in minutes (min.). The results are shown in Table II.

Platelet aggregation induced by collagen and ADP

<img file="FI63409B_D0017.tif" />

Table II

<img file="FI63409B_D0018.tif" />

The following examples illustrate the invention. Temperatures are given in ° C.

Example 1

11,5-Dihydro-3,9-dimethylimidazo [2,1-b] quinazolin-2 (3H) -one

To a solution of 11.8 g of N- (2-amino-3-methylbenzyl) L-alanine ethyl ester in 30 ml of ethanol was added, with stirring at room temperature, a solution of 5.3 g of bromocyanide in 10 ml of ethanol. The reaction mixture was heated to reflux for 1 hour and then evaporated to dryness under reduced pressure. To the residue was added 100 ml of water and made alkaline by adding 3 N ammonium hydroxide with stirring. The mixture was then further stirred for 30 min. and extracted three times with 100 ml of methylene chloride each time. The organic extracts were washed twice with 150 ml of water each time, dried over sodium sulfate and evaporated. The residue was recrystallized from ethanol to give 11,5-dihydro-3,9-dimethylimidazo [2,1-1] quinazolin-2 (3H) -one, m.p. 259-261 °, (ex) = + 15.5 °. (C = 1% in methanol).

Recrystallization of the base thus obtained from 1N hydrochloric acid and acetonitrile (3: 1) gave the hydrochloride, m.p. is 272-275 ° (decomp.).

The starting material was prepared as follows:

To a solution of 91.8 g of L-alanine ethyl ester hydrochloride in 300 ml of absolute ethanol was added dropwise over 30 min. during which time a solution of 120 ml of triethylamine in 200 ml of absolute ethanol. The reaction mixture was heated to 60 ° to give a clear solution. To this solution was added over 1 hour a solution of 55.5 g of 3- (chloromethyl) -2-nitrotoluene in 300 ml of absolute ethanol. The temperature was then raised to 80 ° C and the reaction mixture was stirred overnight at this temperature. It was then evaporated to dryness under reduced pressure and the residue was dissolved in 600 ml of water. The solution was extracted three times with methylene chloride and the extracts were washed successively with water and saturated sodium chloride solution, dried and evaporated. The crude product thus obtained was purified by chromatography on silica gel using methylene chloride / 5% methanol as eluent. N- (3-methyl-2-nitrobenzyl) -L-alanine ethyl ester was obtained as a yellow oil, / 7X_7_D= -36 ° (c = 1% in methanol).

A solution of 26.6 g of N- (3-methyl-2-nitrobenzyl) L-alanine ethyl ester in 100 ml of absolute ethanol was hydrogenated using 2 g of 10% palladium / carbon. Over 5 hours, 6.7 liters of hydrogen were bubbled into the solution. After completion of the hydrogenation, the catalyst was filtered off and the filtrate was evaporated to dryness. There was obtained N- (2-amino-3-methylbenzyl) -L-alanine ethyl ester as a yellow oil, Z / 7_D⁼ 52.6 ° (c = 1% in methanol).

Example 2

Similarly to Example 1, N- (2-amino-3-methylbenzyl) -D-alanine ethyl ester D1,5-dihydro-3,9-dimethylimidazo [2,1-b] quinazolin-2 (3H) -one was obtained. hydrochloride. Melting point 270-275 ° (decomp.). The free base melts at 262-265 °.

Example 3

Similarly to Example 1, N- (2-amino-5-methylbenzyl) -L-alanine ethyl ester gave 1,1'-dihydro-2,7-dimethylimidazo [2,1-b] quinazolin-2 (3H) -one hydrochloride. Light yellow crystals, m.p. is 173-176 °. The free base melts with decomposition at a temperature above 300 °.

Example 4

Similarly to Example 1, N- (2-amino-5-methylbenzyl) -D-alanine ethyl ester gave D1,5-dihydro-3,7-dimethylimidazo [2,1-b] quinazolin-2 (3H) -one hydrochloride. Light yellow crystals, m.p. is 173-176 ° (decomp.). The free base melts with decomposition at 310-314 °.

Example 5

Similarly, as in Example 1, N- (2-amino-6-methylbenzyl) -L-alanine ethyl ester gave L1,5-dihydro-3,6-dimethylimidazo [2,1-b] quinazolin-2 (3H) -one hydrochloride. Colorless crystals of m.p. is 285-288 °. The free base melts to 340 ° above, decomposing.

Example 6

Similarly to Example 1, N- (2-amino-6-methylbenzyl) -D-alanine ethyl ester D1,5-dihydro-3,6-dimethylimidazo [2,1-b] quinazolin-2 (3H) -one was obtained. hydrochloride. Pale14 yellow crystals with m.p. is 287-290 °, (decomp.). The free base melts at a temperature above 340 °.

Example 7

Similarly to Example 1, N- (2-amino-6-methylbenzyl) -L-serine ethyl ester L1,5-dihydro-3-hydroxymethyl-6-methylimidazo [2,1-b] quinazolin-2 (3H) was obtained. -one hydrochloride. Yellow crystals, m.p. is 320-325 ° (decomp.).

Example 8

Similarly, as in Example 1, N- (2-amino-6-methylbenzyl) -D-α-phenylglycine ethyl ester D1,5-dihydro-3-phenyl-6-methylimidazo [2,1-b] quinazolin-2 (3H) -one hydrochloride was obtained. Pale yellow crystals of m.p. is about 320 ° (decomposing).

Example 9

Similarly, as in Example 1, 2-amino-benzyl-L-alanine ethyl ester L1,5-dihydro-3-methylimidazo [2,1-b] quinazolin-2 (3H) -one hydrochloride was obtained. Brown crystals with m.p. is 223-226 °. The free base melts at 300-305 ° with decomposition.

Example 10

Similarly to Example 1, D1,5-dihydro-3-methylimidazo [2,1-b] quinazolin-2 (3H) -one hydrochloride was obtained from 2-amino-benzyl-D-alanine ethyl ester. As yellow crystals of m.p. is 225-227 °. The free base melts at about 300 ° with decomposition.

Example 11

D- and L-6-chloro-1,5-dihydro-3-methylimidazo-32,1-b7quinazolin-2 (3H) -one hydrochloride

To a solution of 11.9 g of N- (2-amino-6-chlorobenzyl) L-alanine ethyl ester in 20 ml of ethanol was added dropwise, with stirring at room temperature, a solution of 5 g of bromocyanide in 20 ml of ethanol. The reaction mixture was then refluxed for 1 hour, evaporated to dryness, 150 ml of water were added to the residue and basified with stirring with 3N NH 4 OH. 30 min. after stirring, the precipitate was filtered and recrystallized from 1N HCl and acetonitrile. 9.1 g (68% of theory) of L-6-chloro-1,5-dihydro-3-methylimidazo [2,1-b] quinazolin-2 (3H) -one hydrochloride were obtained as yellow crystals, m.p. is 260-263 °, E &amp; 'Jq - + 34.2 ° (DMSO)

D-6-chloro-1,5-dihydro-3-methylimidazo [2,1-b] quinazolin-2 (3H) -one hydrochloride was similarly obtained from N- (2-amino-6-chlorobenzyl) -D-alanine ethyl ester, m.p. . 263-266 °, / o &lt;7_d = -23.9 ° (DMSO); the melting point of the free base is 275-280 °.

The starting material can be prepared as follows:

To 18.24 g of L-alanine ethyl ester hydrochloride in 60 ml of ethanol was added dropwise a mixture of 25 ml of triethylamine per ml of ethanol, and the mixture was heated to 80 °. A solution of 15 gc * -bromo-2-chloro-6-nitrotoluene in 60 ml of ethanol was added dropwise to the resulting solution. The mixture was stirred overnight at 80 ° C and then evaporated to dryness, 150 ml of deionized water were added to the residue and extracted twice with 100 ml of methylene chloride. The methylene chloride extracts were washed with water, dried and evaporated. The product thus obtained was purified by chromatography on silica gel using methylene chloride / 5% methanol. 15.75 g (91% of theory) of N- (2-chloro-6-nitrobenzyl) -L-alanine ethyl ester were obtained, n = 1.5267.

N- (2-chloro-6-nitrobenzyl) -D-alanine ethyl ester was obtained from D-alanine ethyl ester and &lt;X-bromo-2-chloro, respectively.

From 6-nitrotoluene, ca._Q :1,5247.

A solution of 14.3 g of N- (2-chloro-6-nitrobenzyl) -Lalanine ethyl ester in 50 ml of absolute ethanol was hydrogenated using 1 g of Raney nickel. After completion of the hydrogenation, the catalyst was filtered off and the filtrate was evaporated to dryness.

12.6 g (99% of theory) of N- (2-amino-6-chloro-22-benzyl) -L-alanine ethyl ester were obtained, n_D = 1,5430.

N- (2-amino-6-chlorobenzyl) -D-alanine ethyl ester was obtained in a similar manner by hydrogenation of N- (2-chloro-6-nitrobenzyl) -D-alanine ethyl ester, n_D = 1,5405.

Example 12

In a similar manner to Example 11, the following compounds were prepared:

D-6,7-dichloro-1,5-dihydro-3-methylimidazo [2,1-b] quinazolin-2 (3H) -one hydrochloride, m.p. &gt; 290 °,

D-7-bromo-1,5-dihydro-3-methylimidazo [2,1-b] quinazolin-2 (3H) -one hydrochloride, m.p. 268-270 °,

L-7-bromo-1,5-dihydro-3-methylimidazo [2,1b] quinazoline-2 (3 H) -one hydrochloride, m.p. 280-284 ° (decomp.),

L-6-chloro-7-methoxy-1,5-dihydro-3-methylimidazo [2,1-b] quinazolin-2 (3H) -one hydrochloride, m.p. &gt; 280 °.

Example 13

In a similar manner to Example 11, the following compounds were prepared:

From N- (2-chloro-6-nitrobenzyl) -3-phenyl-D-alanine ethyl ester, = -21.2 ° (c = 1% in ethanol) N- (2-amino-6-chlorobenzyl) -3-phenyl-D -alanine ethyl ester, _D = + 40.7 ° (8 = 1% in ethanol), D-3-benzyl-6-chloro-1,5-dihydroimidazo [2,1-b] quinazolin-2 (3H) -one hydrochloride, m.p. 260-265 ° (dec.); base m.p. 270 ° -275 ° (dec.);

From N- (2-chloro-6-nitrobenzyl) -D-leucine ethyl ester via N- (2-amino-6-chlorobenzyl) -D-leucine ethyl ester, = + 8.5 ° (c = 1% in ethanol) D -6-chloro-1,5-dihydro-3-isobutylimidazo [2,1-b] quinazolin-2 (3H) -one hydrochloride, m.p. 290-293 °; base m.p. 280-285 °;

N- (2-chloro-6-nitrobenzyl) -D-serine ethyl ester, Z / X_7_d = 2.7 ° (c = 1% in ethanol), via N-2- (amino-6-chlorobenzyl) D-serine ethyl ester m.p. 73-75 °, Zc * 7_D = + 65.5 ° (c = 1% in ethanol), D-6-chloro-3-hydroxymethyl-1,5-dihydroimidazo [2,1-b] quinazolin-2 (3H) -one hydrochloride, m.p. &gt; 300 ° (decomposed);

DN- (2-chloro-6-nitrobenzyl) -2-phenylglycine ethyl ester, CcAj _D - -21 ° (c = 1% in ethanol), via DN- (2-amino-6-chlorobenzyl) -2-phenylglycine ethyl ester, / cx /_D ~ -4.5 ° (c = 1% in ethanol) D-6-chloro-3-phenyl-1,5-dihydroimidazo [2,1-b] quinazolin-2 (3H) -one hydrochloride, m.p. &gt; 300 ° (decomposed); base m.p. 260-265 ° (dec.).

Example 14

D-6-chloro-1,5-dihydro-3-methylimidazo [2,1b] quinazoline

2 (3H) -one hydrochloride

A mixture of 6 g of ethyl D-2,5-dichlorooc-methyl-3 (4H) -quinazoline acetate, 20 ml of absolute ethanol and 25 ml of 5% alcoholic ammonia was heated in a pressure tube at 110 ° overnight. The pressure tube was cooled in a refrigerator and opened. The formed crystal porridge was suction filtered and washed with cold ethanol. The obtained crystals were dissolved in 1N hydrochloric acid and filtered. The filtrate was evaporated to dryness and the residue was recrystallized from 1N hydrochloric acid to give D-6-chloro-1,5-dihydro-3-methylimidazo [2,1-b] quinazolin-2 (3H) one hydrochloride from acetonitrile. (4.3 g 74% of theory), m.p. 275-278 °.

The starting material can be prepared as follows:

To a mixture of 18.24 g of D-alanine ethyl ester hydrochloride in 60 ml of ethanol was added dropwise a mixture of 25 ml of triethylamine in 60 ml of ethanol, and the reaction mixture was heated to 80 ° C. A solution of 15 g of 2-chloro-6-nitrobenzyl bromide in 60 ml of ethanol was added dropwise to the resulting solution. The mixture was stirred overnight at 80 ° C, then evaporated to dryness, 150 ml of deionized water were added to the residue and extracted twice with 100 ml of methylene chloride. The methylene chloride extracts were washed with water, dried over sodium sulfate and evaporated. The product thus obtained was purified by chromatography on silica gel using methylene chloride / 5% methanol. 16 g (93% of theory) of N- (2-chloro-6-nitrobenzyl) -D-alanine ethyl ester were obtained, n²³ = -6,9° (_c =] _%, c₂B₅oh).

A solution of 14.3 g of N- (2-chloro-6-nitrobenzyl) -Dalanine ethyl ester in 50 ml of ethanol was hydrogenated using 1 g of Raney nickel. Within 2 hours, 3.35 liters of hydrogen had been introduced into the solution. The catalyst was then filtered off and the filtrate was evaporated to dryness. 12.6 g (99% of theory) of N- (2-amino-6-chlorobenzyl) -D-alanine ethyl ester were obtained, n²³ = 1.5405, £ X7_D = 55.8 ° (c = 1%, CH 2 OH).

To a solution of 71.75 g of N- (2-amino-6-chlorobenzyl) D-alanine ethyl ester in 400 ml of dry tetrahydrofuran was added 52 g of N, N'-carbonyldiimidazole portionwise with stirring under a nitrogen atmosphere. The mixture was stirred for 2 hours and heated at reflux for 18 hours and evaporated to dryness, and the residue was extracted with 1500 ml of methylene chloride, the organic phase was washed twice with 400 ml of 1N hydrochloric acid and then with 400 ml of water, dried and evaporated. The oil thus obtained was purified by chromatography on silica gel using methylene chloride / 5% methanol. Yield: 79 g (99% of theory) of ethyl D-5-chloro-1,4-dihydro-cis-methyl-2-oxo-3 (2H) -quinazoline acetate, = -40.8 °, (c = 1% , (CH 2 Cl 2).

50.9 g of ethyl D-5-chloro-1,4-dihydro-o-methyl-2-oxo-3 (2H) -quinazoline acetate were dissolved in 135 ml of phosphorus oxychloride and heated to 110 ° with stirring for 3 hours. After cooling, the reaction mixture was evaporated to dryness, the residue was dissolved in 250 ml of chloroform, the solution was diluted with 300 ml of ice water and the pH was adjusted to 7-8 by dropwise addition of 40% sodium hydroxide. The chloroform phase was separated, dried and evaporated. The product was purified by chromatography on silica gel using methylene chloride / 5% methanol. Rule:

37.4 g (70% of theory) of ethyl D-2,5-dichloro-cX22 methyl-3 (4H) -quinazoline acetate, ηθ = 1.5775.

Example 15

D-7-bromo-1,5-dihydro-3-methylimidazo [2,1-b] quinazolin-2 (3H) -one hydrochloride

To a solution of 5 g of D1,5-dihydro-3-methylimidazo [2,1b] quinazolin-2 (3H) -one in 80 ml of glacial acetic acid was added dropwise 1.5 ml of bromine. The mixture was stirred for 1 1/2 hours at room temperature, 100 ml of water were added, concentrated to 30 ml, diluted once more with 100 ml of water, basified with 3N ammonium hydroxide, washed and filtered. The resulting product was washed with water and recrystallized from 100 mL of 2N HCl. 3.9 g (56%) of D-7-bromo-1,5-dihydro-3-methylimidazo [2,1b] quinazolin-2 (3H) -one hydrochloride were obtained, m.p. 268-270 °.

Example 16

Similarly to Example 15, 4.7 g of L-1,5-dihydro-3-methylimidazo [2,1b] quinazolin-2 (3H) -one is brominated to 4.2 g (64%) of L-7-bromo-1 , 5-dihydro-3-methylimidazo [2,1-b] quinazolin-2 (3H) -one hydrochloride, m.p. 280-284 ° (dec.).