Disclosed herein are new 4-aryl-benzazocine-2,6-diones of Formula I ##STR1## in which R.sup.1 is phenyl, naphthyl or phenyl or naphthyl substituted by one to three moieties selected from fluoro, chloro, bromo, and alkyl or alkoxy of 1 to 4 carbon atoms; PA0 R.sup.2 is --R.sup.3 --NR.sup.4 R.sup.5, wherein R.sup.3, R.sup.4 and R.sup.5 are, independently, straight or branched chain alkyl groups of 1 to 4 carbon atoms or R.sup.4 and R.sup.5 are concatenated to form nitrogen ring having 3 to 8 carbon atoms; and PA0 X and Y are, independently, hydrogen, alkyl or alkoxy of 1 to 4 carbon atoms, dialkylamino or dialkyl-carboxamido wherein each alkyl group has 1 to 4 carbon atoms, cyano, alkylacyl of 1 to 4 carbon atoms, fluoro, chloro, nitro, dialkylsulfonamido wherein each alkyl group has 1 to 4 carbon atoms, or alkylsulfonyl of 1 to 4 carbon atoms, or a pharmaceutically acceptable salt thereof. The compounds of Formula I are useful as anti-arrhythmic agents.

The invention described herein concerns new chemical compositions and, in 
particular compounds having the formula I. 
##STR2## 
In formula I, R.sup.1 may be aryl (e.g., phenyl, naphthyl) or substituted 
aryl (e.g., chlorophenyl, trimethyloxyphenyl, methylnaphthyl). R.sup.2 is 
the group: 
##STR3## 
wherein R.sup.3, R.sup.4 and R.sup.5 are lower straight-chain or lower 
branched-chain alkyl. By "lower alkyl" is meant an alkyl group having 1-8 
carbon atoms. R.sup.4 and R.sup.5 can also be concatenated to form a 
heterocyclic nitrogen ring containing up to 8 carbon atoms. X and Y may be 
hydrogen, lower alkyl, lower alkoxy, lower alkylamino, carboxamido, cyano, 
lower acyl, halogen, nitro, sulfonamido, or lower alkylsulfonyl. The 
compounds of Formula I of the invention exhibited antiarrhythmic and 
calcium antagonism in standard pharmacological procedures. The invention 
also includes a method of treating mammals, including man, afflicted with 
heart arrhythmia by administering an amount of a compound of Formula I 
effective to alleviate the arrhythmia. 
BACKGROUND OF THE INVENTION 
Benzazocine-2,6-diones unsubstituted on the dione ring were reported by 
Jones and Tringham, Journal of the Chemical Society Perkins, I, 1280-1283 
(1975), as intermediates for possible anti-inflammatory agents. The 
desired end products therein had a carboxylic acid group in place of the 
oxo group in the six position and an aralkyl group on the nitrogen--and 
were found to exhibit no significant anti-inflammatory activity. 
3-Amino-benzazocine-2,6-diones having angiotensin converting enzyme 
inhibition and hypotensive properties are disclosed in European Patent 
Publication EP-119-161-A to Ciba-Geigy (Derwent Abstract 84-232700/38). 
These compounds are further substituted on the nitrogen atom by a 
methylene carboxy group. 
The new compounds of the invention differ from the above in having a 4-aryl 
or heteroaryl substituent and 1-alkyleneamino substituent. Further, the 
new compounds of the invention exhibits pharmacological properties as 
anti-arrhythmic agents. 
DETAILED DESCRIPTION OF THE INVENTION 
The first aspect of this invention provides new 
4-aryl-benzazocine-2,6-diones of Formula I 
##STR4## 
in which R.sup.1 is phenyl, naphthyl or phenyl or naphthyl substituted by 
one to three moieties selected from fluoro, chloro, bromo, and alkyl or 
alkoxy of 1 to 4 carbon atoms; 
R.sup.2 is --R.sup.3 --NR.sup.4 R.sup.5, wherein R.sup.3, R.sup.4 and 
R.sup.5 are, independently, straight or branched chain alkyl groups of 1 
to 4 carbon atoms or R.sup.4 and R.sup.5 are concatenated to form nitrogen 
ring having 3 to 8 carbon atoms; and 
X and Y are, independently, hydrogen, alkyl or alkoxy of 1 to 4 carbon 
atoms, dialkylamino or dialkylcarboxamido wherein each alkyl group has 1 
to 4 carbon atoms, cyano, alkylacyl of 1 to 4 carbon atoms, fluoro, 
chloro, nitro, dialkylsulfonamido wherein each alkyl group has 1 to 4 
carbon atoms, or alkylsulfonyl of 1 to 4 carbon atoms, 
or pharmaceutically acceptable salts thereof. 
A second aspect of this invention provides a method of treating heart 
arrhythmia in mammals, including man, having a heart arrhythmia, 
comprising administering to such mammal in need thereof an amount of a 
compound of Formula I effective to alleviate said arrhythmia. 
Preferred compounds of both aspects of the invention are those in which: 
R.sup.1 is phenyl or naphthyl unsubstituted or substituted as described 
for Formula I; R.sup.3 is methylene or ethylene; R.sup.4 and R.sup.5 are 
methyl or ethyl or --NR.sup.4 R.sup.5 is pyrrolidine, piperidine, or 
hexamethylimine ring; and X and Y are hydrogen, lower alkyl or lower 
alkoxy of 1 to 3 carbon atoms, fluoro, chloro, or X is one of the 
foregoing and Y is hydrogen. Particularly preferred compounds of both 
aspects of the invention are those in which R.sup.1 is phenyl, naphthyl, 
methoxyphenyl, chlorophenyl, trimethyloxyphenyl, or methylnaphthyl; 
R.sup.3 is ethylene; R.sup.4 and R.sup.5 are methyl; and X and Y are 
hydrogen. 
The following reaction scheme depicts suitable processes for preparing the 
compounds of Formula I 
##STR5## 
In process step A, an appropriately substituted phenylhydrazine (II) is 
reacted with an appropriately substituted cyclopentanone (III) under 
acidic conditions. Suitable reaction conditions are described by R. B. 
Perni and G. Gribble in Orgaic Preparations and Processes International, 
14, 343-346 (1982). A mixture of 1 and 2 substituted (R.sup.1) 
1,2,3,4-tetrahydro-cyclopentyl[b]indoles is obtained, and the desired 2 
isomer (IV) is isolated for step B. (Or, separation of the desired isomer 
may take place at the end of steps B or C). 
In step B, oxidation of the 
2-substituted-1,2,3,4-tetrahydro-cyclopentyl[b]indole thus obtained may be 
accomplished using m-chloroperbenzoic acid as an oxidant in accordance 
with the procedure of V. Dave and E. W. Warnoff, Canadian Journal of 
Chemistry, 50, 3392-3396 (1972). Other suitable oxidation conditions 
compatible with values of R.sup.1, X and Y other than those exemplified 
are known to the art-skilled organic chemist. In step C, the R.sup.2 
moiety may be conveniently introduced. For example, the appropriate 
dialkylaminoalkyl halide (chloride or bromide) or pyrrole or pyridyl-alkyl 
halide may be reacted with V in an inert solvent, such as toluene, in the 
presence of a suitable amount of sodium hydride to yield the desired 
product of Formula I. 
The pharmacologically acceptable salts of the compounds of this invention 
are prepared directly by neturalization of the free base. These salts may 
be formed with organic or inorganic acids such as hydrochloric, 
hydrobromic, phosphoric, sulfuric, sulfurous, nitric, methylsulfonic, 
acetic, maleic, succinic, fumaric, tartaric, citric, salicylic, lactic, 
naphthalene-sulfonic acid, and the like. 
The compounds of this invention demonstrate antiarrhythmic activity when 
tested in the standard experimental animal in accordance with the 
following procedure [Bergey, J. L., et al., European Journal of 
Pharmacology, 81, 205-216 (1982)]: 
Rats weighing between 400-500 gms were anesthesized with 35-40 mg/kg sodium 
pentobarbital intraperitoneally. Rats were close-clipped on the neck and 
left thorax prior to cannulation of the jugular vein and carotid artery 
for measurement of arterial blood pressure and injection of drug. A 
tracheotomy was performed and respiration provided by a Harvard Model 681 
respirator at a rate of approximately 55 cycles/min and a volume of 4 cc 
per cycle. The rat was then placed upon its right side and the heart was 
exposed by making an incision and separating the ribs. 4-0 Silk on taper 
RB-1 needle was passed under the left anterior descending coronary artery 
(LAD) at a location just under the tip of the left atrial apendage. The 
suture was left to be tied upon occlusion. 
The rat was allowed to stabilize for 5 to 15 minutes before the 
administration of drug as a bolus via the cannulated jugular vein. The 
total drug dose volume is kept constant between 0.20-0.25 ml. Fifteen 
minutes after dosing, the LAD was occluded by tying the suture. This 
procedure provokes severe ventricular arrhythmias, terminating in 
ventricular fibrillation and death in at least about 65 percent of animals 
given vehicle only. The development and progression of ventricular 
arrhythmia is monitored for a period of 20 minutes. Lead II ECG and 
cardiotachometer output were recorded on a Beckman R612 recorder. 
Mean arterial pressure (MAP) is monitored throughout the experiment, and 
the following values recorded: (1) MAP prior to drug, (2) maximal change 
in MAP following drug and before LAD occlusion, and (3) MAP just prior to 
LAD occlusion. Changes in cardiac electrical activity are determined from 
the Lead II electrocardiogram. The dysrhythmias are scored as follows: (1) 
normal sinurhythm, (2) isolated premature ventricular complexes, (3) 
non-sustained ventricular tachycardia (repetitive beats of ventricular 
origin lasting 15 sec.), (4) sustained ventricular tachycardia (repetitive 
ventricular activity lasting 15 sec.), (5) self-terminating or reversible 
ventricular fibrillation (VFrev), and (6) irreversible VF (VF irrev. 
death). The incidence of death in the drug-treated group is then compared 
to that in the untreated control group (generally 65%). Five animals are 
included in each drug group. 
Arrhythmias scores are calculated for each group of animals for purposes of 
obtaining more quantitative rankings for anti-arrhythmic efficacy. The 
equation, 
##EQU1## 
is used, where A=fraction of animals with a certain kind of arrhythmia 
(e.g., ventricular fibrillation, sustained ventricular tachycardia) and AS 
is the arbitrary score assigned to that arrhythmia: 
______________________________________ 
A AS 
______________________________________ 
(a) no arrhythmia -5 
(b) isolated premature beats (PVC's) 
+5 
(c) non-sustained ventricular tachycardia 
+10 
(d) sustained ventricular tachycardia 
+20 
(e) reversible ventricular fibrillation 
+40 
(f) death +50 
______________________________________ 
Thus, for the purpose of these coronary ligation (C.L.) experiments, a 
score from -5 (no arrhythmia) to 50 (death) is assigned to the response of 
each rat in a test group, based upon the number, type and severity of each 
response. The sum of the percent of animals at each response level times 
the point score assigned that response level equals the score value of the 
compound being tested. The lower the score, the more active the compound 
in preventing ventricular dysrhythmia. 
In this procedure the compound of Example 8 had a score of 15 when 
administered at 10 mg/kg of body weight. This activity score is considered 
moderate. The corresponding 
1-[2-(dimethylamino)ethyl]-4,5-dihydro-5-(4-methoxyphenyl)-1-benzazocine-2 
,6-(1H,3H)-dione was inactive when similarly tested. 
This pharmacological property of the compounds of the invention indicates 
that they would be useful in the treatment of cardiac arrhythmias and 
conditions characterized by coronary artery occlusion and the resulting 
myocardial ischemia. For that purpose, the compounds may be administered 
orally or parenterally in suitable dosage forms compatible with the route 
of administration, whether oral, intraperitoneal, intramuscular, 
intravenous, intranasal, buccal, etc. 
For treatment of such conditions the compounds of the invention on their 
pharmacologically acceptable salts may be administered in doses of 1 to 
100 milligrams per kilogram of the host body weight in single or plural 
doses as needed to relieve the arrhythmic dysfunction. 
The specific dosage regimen for a given patient will depend upon age, 
patholigical state, severity of dysfunction, size of the patient, etc. 
Oral administration is performed with either a liquid or solid dosage unit 
in any conventional form such as tablets, capsules, solutions, etc. which 
comprise a unit dose (e.g. from about 25 milligrams to about 4 grams) of 
the active ingredient alone or in combination with adjuvants needed for 
conventional coating, tableting, solubilizing, flavoring or coloring. 
Parenteral administration with liquid unit dosage forms may be via sterile 
solutions or suspensions in aqueous or oleagenous medium. Isotonic aqueous 
vehicle for injection is preferred with or without stabilizer, 
preservatives and emulsifiers. 
Preparation of the compounds of the invention and their salts is further 
illustrated by the following examples.

EXAMPLE 1 
1,2,3,4-Tetrahydro-2-(4-Methoxyphenyl)Cyclopent[b]Indole 
A mixture of 3-(4-methoxyphenyl)-1-cyclopentanone (15.22 g) and phenyl 
hydrazine hydrochloride (11.57 g) in glacial acetic acid (112 ml) under 
nitrogen was stirred magnetically and slowly heated to 90.degree. with a 
heating mantle. A white precipitate, which formed at approximately 
60.degree., dissolved to give a red solution as the temperature rose 
exothermically to 110.degree.. As soon as the solid had dissolved, the 
heating mantle was removed and the temperature allowed to return to 
90.degree. for 1 hr. The cooled solution was poured into 400 ml of water. 
After refrigeration, the supernatant liquid was filtered. The filter pad 
and residual material were dissolved in chloroform and the solution was 
washed with saturated sodium bicarbonate solution. The dried (MgSO.sub.4) 
solution was evaporated to a syrup which was subjected to an oil pump 
vacuum; wt. 19.4 g (92%). This material was chromatographed on a column 
(60.times.7.6 cm) of silica gel prepacked in chloroform. Elution with 
chloroform afforded a mixture of the titled product and 
1,2,3,4-tetrahydro-1-(4-methoxyphenyl)-cyclopent[b]indole in a ratio of 
3:2 as determined by a reverse phase HPLC system (see Example 2). After 
solvent removal the residual syrup was coevaporated with acetonitrile to 
give 11.90 g (56.5%) of a red syrup which began to crystallize on 
standing. Crystallization from acetonitrile-water (seeding) gave crude 
product; wt. 5.25 g (24.9%), mp=107.degree.-109.degree.. Recrystallization 
from acetonitrile-water gave the titled product as pale yellow crystals, 
wt. 4.39 g, mp=109.degree.-111.degree.. 
Analysis: C.sub.18 H.sub.17 NO: Calculated: C, 82.10; H, 6.51; N, 5.32. 
Found: C, 82.24; H, 6.58; N, 5.14. 
The mother liquor from the first crystallization of the titled product was 
evaporated to a syrup and subjected to an oil pump vacuum; wt. 6.7 g. The 
ratio of titled product to 
1,2,3,4-tetrahydro-1-(4-methoxyphenyl)cyclopent[b]indole in this material 
was 36:64 as determined by HPLC. 
EXAMPLE 2 
1,2,3,4-Tetrahydro-1-(4-Methoxyphenyl)Cyclopent[b]Indole 
The material from the mother liquor obtained in Example 1 was subjected to 
preparative reverse phase chromatography on two C.sub.18 Prep Pak 500 
(Waters) columns in tandem. Elution was with acetonitrile-water (47:53). 
Fractions (usually 1 l.) were monitored by anaytical HPLC on a Waters 
$-Bondpak C18 column using acetonitrile-water (1:1) as solvent. The first 
component to issue from the column was the titled compound. Appropriate 
fractions were combined and evaporated until an emulsion was obtained. 
After addition of salt and brine to the mixture it was extracted several 
times with dichloromethane. The organic extract was washed with brine and 
dried (MgSO.sub.4). The resulting syrup was coevaporated with acetonitrile 
and crystallized from acetonitrile-water; wt. 2.75 g (13.1%), 
mp=107.degree.-109.degree.. Recrystallization from acetonitrile-water 
affored pure titled product as pale yellow crystals; wt. 2.32 g, 
mp=108.degree.-109.degree.. 
Analysis for: C.sub.18 H.sub.17 NO: Calculated: C, 82.10; H, 6.51; N, 5.32. 
Found: C, 82.49; H, 6.47; N, 5.37. 
Later fractions from the preparative HPLC were similarly processed to give 
additional 1,2,3,4-tetrahydro-2-(4-methoxyphenyl)cyclopent[b]-indole; wt. 
1.24 g (5.9%), mp=110.degree.-112.degree.. 
Analysis for: C.sub.18 H.sub.17 NO: Calculated: C, 82.10; H, 6.51; N, 5.32. 
Found: C, 81.91; H, 6.52; N, 5.29 
EXAMPLE 3 
1,2,3,4-Tetrahydro-2-(4-Methoxyphenyl)Cyclopent[b]Indole 
A mixture of 3-(4-methoxyphenyl)-1-cyclopentanone (15.22 g) and phenyl 
hydrazine hydrochloride (11.57 g) in glacial acetic acid (112 ml) under 
nitrogen was stirred magnetically and slowly heated to 90.degree. with a 
heating mantle. A white precipitate, which formed at approximately 
60.degree., dissolved to give a red solution as the temperature rose 
exothermically to 110.degree.. As soon as the solid had dissolved, the 
heating mantle was removed and the temperature allowed to return to 
90.degree.. The temperature was then maintained at 90.degree. for 1 hr. 
The cooled solution was poured into 400 ml of water. After refrigeration, 
the supernatant was filtered. The filter pad and residual material were 
dissolved in dichloromethane and the solution was washed with saturated 
sodium bicarbonate solution. The dried (MgSO.sub.4) solution was 
evaporated to a syrup which was subjected to oil pump vacuum; wt. 20.1 g 
(95%). 
This crude material in dichloromethane was applied to a column 
(79.times.8.4 cm) of silica gel prepacked in dichloromethane. Elution with 
dichloromethane afforded a mixture of the titled product and 
1,2,3,4-tetrahydro-1-(4-methoxyphenyl)cyclopent[b]indole. After solvent 
removal, the residual yellow syrup (12.5 g) was coevaporated with 
acetonitrile to obtain a syrup which was crystallized from 
acetonitrile-water (seeding); wt. 5.99 g (28.4%), 
mp=106.degree.-109.degree.. Two crystallizations gave pure titled compound 
having mp=111.degree.-112.degree.. 
Analysis for: C.sub.18 H.sub.17 NO: Calculated: C, 82.10; H, 6.51; N, 5.31. 
Found: C, 81.93; H, 6.68; N, 5.13. 
The mother liquor from the first crystallization of the titled product was 
evaporated to a syrup which was coevaporated with acetonitrile. The yellow 
resulting syrup was dried under oil pump vacuum; wt. 6.3 g. This material 
was used in Example 4. 
EXAMPLE 4 
4,5-Dihydro-5-(4-Methoxyphenyl)-1-Benzazocine-2,6(1H,3H)-Dione 
To a stirred solution of the syrupy material (6.3 g) isolated from the 
mother liquors in Example 3 in dichloromethane (150 ml) at 10.degree. was 
added slowly m-chloroperbenzoic acid (14.6 g) in dichloromethane (350 ml) 
and the mixture was stirred at room temperature overnight. The solution 
was washed consecutively with 10% sodium sulfite solution, saturated 
sodium bicarbonate solution and brine and dried (MgSO.sub.4). Evaporation 
gave a residue which was subjected to an oil pump vacuum; wt. 6.6 g. 
Slurrying with acetone gave a tan solid, wt. 2.38 g (10%), 
mp=230.degree.-233.degree.. Recrystallization from acetonitrile gave 1.60 
g [6.8% from 3-(4-methoxyphenyl)-1-cyclopentanone] of pure titled 
compound, mp=245.degree.-246.degree.. 
Analysis for: C.sub.18 H.sub.17 NO.sub.3 : Calculated: C, 73.20; H, 5.80; 
N, 4.74. Found: C, 73.24; H, 5.75; N, 4.76. 
EXAMPLE 5 
1,2,3,4-Tetrahydro-2-(4-Methoxyphenyl)Cyclopent[b]Indole 
A mixture of 3-(4-methoxyphenyl)-1-cyclopentanone (15.21 g) and 
phenylhydrazine hydrochloride (11.56 g) in glacial acetic acid (110 ml) 
under nitrogen was stirred magnetically and slowly heated to 90.degree. 
with a heating mantle. A white precipitate, which formed at approximately 
60.degree., dissolved to give a red solution as the temperature rose 
exothermically to 110.degree.. As soon as the solid had dissolved, the 
heating mantle was removed and the temperature allowed to return to 
90.degree.. The temperature was then maintained at 90.degree. for 1 hour. 
The cooled solution was poured into water (400 ml). After refrigeration 
under nitrogen overnight, the supernatant liquid was filtered. The filter 
pad and residual material were dissolved in dichloromethane and the 
solution was washed with saturated sodium bicarbonate solution. The dried 
(MgSO.sub.4) solution was evaporated to a syrup which was subjected to an 
oil pump vacuum; wt. 18.7 g. This material in dichloromethane was 
chromatographed on a column of silica gel prepacked in dichloromethane. 
Elution with dichloromethane afforded a mixture of the titled product and 
1,2,3,4-tetrahydro-1-(4-methoxyphenyl)cyclopent[b]indole. After solvent 
removal, the residual yellow syrup was crystallized from ethanol-hexane to 
give the titled product as pale yellow crystals; wt. 5.14 g (24.4%), 
mp=108.degree.-110.degree.. 
Analysis for: C.sub.18 H.sub.17 NO: Calculated: C, 82.10; H, 6.51; N, 5.32. 
Found: C, 82.15; H, 6.59; N, 5.58. 
The mother liquor from the crystallization of the titled product was 
evaporated to a solid which was subjected to an oil pump vacuum; wt.=5.0 
g. The ratio of the titled product to 
1,2,3,4-tetrahydro-1-(4-methoxyphenyl)cyclopent[b]indole in this material 
was 18:82 as determined by HPLC. 
EXAMPLE 6 
4,5-Dihydro-5-(4-Methoxyphenyl)-1-Benzazocine-2,6-(1H,3H)-Dione 
To a stirred solution of the material (5.0 g) obtained from the mother 
liquor of Example 5 in dichloromethane (100 ml) at 10.degree. under 
nitrogen was slowly added m-chloroperbenzoic acid (11.5 g) in 
dichloromethane (300 ml). The reaction was allowed to warm to room 
temperature and stirred for 18 hrs. The reaction solution was washed 
consecutively with 10% sodium sulfite solution, saturated sodium 
bicarbonate solution and brine. The dried (MgSO.sub.4) solution was 
evaporated to a tacky solid; wt. 6.1 g. Slurrying with acetone gave a tan 
solid which was collected on a filter; wt. 2.2 g. Recrystallization from 
acetonitrile gave pure titled product; wt.=1.65 g (7% from 
3-(4-methoxyphenyl)-1-cyclopentanone), mp=244.degree.-245.degree.. 
Analysis for: C.sub.18 H.sub.17 NO.sub.3 : Calculated: C, 73.20; H, 5.80; 
N, 4.74. Found: C, 73.16; H, 5.69; N, 5.11. 
EXAMPLE 7 
4,5-Dihydro-4-(4-Methoxyphenyl)-1-Benzazocine-2,6-(1H,3H)-Dione 
To 1,2,3,4-tetrahydro-2-(4-methoxyphenyl)cyclopent[b]indole (10.53 g) in 
dichloromethane (300 ml) cooled in ice was added m-chloroperbenzoic acid 
(18.68 g) in dichloromethane (500 ml) dropwise so that the reaction 
temperature remained between 0.degree. and 10.degree.. The ice bath was 
removed and the mixture stirred magnetically at room temperature 
overnight. The solution was washed consecutively with sodium sulfite 
solution, saturated sodium bicarbonate solution and dried (MgSO.sub.4). 
Evaporation gave a dark foam, which was crystallized from acetone (dry ice 
cooling). The crude titled product was collected on a filter and washed 
with acetone chilled in dry ice; wt. 5.15 g (44%, crop 1), 
mp=136.degree.-138.degree.. The mother liquor was evaporated to a syrup 
which gave 9.27 g of a foam when subjected to an oil pump vacuum. This 
material in dichloromethane was applied to a column of silica gel 
prepacked in dichloromethane. Elution was with dichloromethane, followed 
by dichloromethane-ethyl acetate (9:1) to remove the product. Evaporation 
of appropriate fractions gave a foam which was crystallized from acetone; 
wt. 1.62 g (15%, crop 2), mp=137.degree.-139.degree.. The mother liquor 
gave an additional 0.3 g (2%, crop 3) of product, 
mp=136.degree.-138.degree.. The three crops of crystals were combined and 
recrystallized from acetone to give pure titled product; wt. 6.14 g (52%), 
mp=138.degree.-140.degree.. 
Analysis for: C.sub.18 H.sub.17 NO.sub.3 Calculated: C, 73.20; H, 5.80; N, 
4.74. Found: C, 73.54; H, 5.78; N, 4.72. 
EXAMPLE 8 
1-[2-(Dimethylamino)Ethyl]-4,5-Dihydro-4-(4-Methoxy)-1-Benzazocine-2,6(1H,3 
H)-Dione, Maleate (1:1) 
To azeotropically dried toluene (90 ml) was added 
4,5-dihydro-4-(4-methoxyphenyl)-1-benzazocine-2,6-(1H,3H)-dione (3.84 g) 
and 60% sodium hydride in mineral oil (0.633 g) and the mixture stirred 
magnetically under a nitrogen atmosphere at room temperature overnight. To 
the mixture was addd freshly prepared N,N-dimethylaminoethyl chloride (5.1 
g) dropwise and the mixture magnetically stirred and heated at 80.degree. 
(under reflux) for 1 hour. A further 5.1 g of N,N-dimethylaminoethyl 
chloride was added and the mixture was stirred and heated at 80.degree. 
for a further 1 hour. The mixture was cooled in ice and filtered through 
sintered glass. (The material on the filter was discarded.) The filtrate 
was evaporated to give a mixed oil which was subjected to an oil pump 
vacuum. This material was dissolved in ether and the solution filtered 
through Celite. The filtrate was evaporated to a biphasic oil which was 
subjected to an oil pump vacuum, wt. 4.88 g. To this material was added 
acetone (30 ml) and fumaric acid (1.55 g) and the mixture was heated to 
boiling. A crude fumarate salt of the titled product crystallized from the 
resulting solution; wt. 4.87 (78%), mp=197.degree.-200.degree.. 
Recrystallization from methanol-acetone gave a purified fumarate salt, 
wt.=4.27 g, mp=199.degree.-201.degree.. 
A portion of the fumarate salt (4.23 g) was stirred with saturated sodium 
bicarbonate solution and ether until the solid had dissolved. The aqueous 
layer was separated and washed two more times with ether. The ether 
extract and washings were washed with brine and dried (MgSO.sub.4). 
Evaporation of the solvent gave an oil which was subjected to an oil pump 
vacuum; wt. 3.14 g. To this material (3.14 g) was added maleic acid (0.995 
g) and acetone (6 ml) and the mixture warmed to achieve solution. Addition 
of ether (seeding) and acetone (as needed) caused the crystallization of a 
maleate salt; wt. 3.47 g (56%), mp=122.degree.-124.degree.. The mother 
liquor deposited further crystals; wt. 0.23 g., 
mp=122.degree.-124.degree.. Recrystallization of both crops of crystals 
from acetone-ether gave pure titled product, wt. 3.52 g (57%), 
mp=123.degree.-125.degree.. 
Analysis for: C.sub.22 H.sub.26 N.sub.2 O.sub.3.C.sub.4 H.sub.4 O.sub.4 : 
Calculated: C, 64.72; H, 6.27; N, 5.81. Found: C, 64.43; H, 6.26; N, 5.92. 
EXAMPLE 9 
1-[2-(Dimethylamino)Ethyl]-4,5-Dihydro-5-(4-Methoxyphenyl)-1-Benzazocine-2, 
6(1H,3H)-Dione 
To azeotropically dried 
4,5-Dihydro-5-(4-methoxyphenyl)-1-benzazocine-2,6(1H,3H)-dione (1.80 g) in 
toluene (40 ml) was added 60% sodium hydride in mineral oil (0.27 g) and 
the mixture stirred under nitrogen at room temperature overnight. The 
slurry was stirred and heated to 70.degree. for 15 minutes, and the 
freshly prepared N,N-dimethylaminoethyl chloride (1.25 g) was slowly 
added. After a half an hour at 70.degree., a further 1.25 g of 
N,N-dimethylaminoethyl chloride was added. The temperature was then raised 
to 90.degree. and maintained for 3 hours. The cooled reaction mixture was 
filtered through sintered glass and the filtered solid discarded. The 
filtrate was evaporated and the residue was triturated with ether. The 
resulting white solid was collected on a filter; wt. 1.58 g (72%), 
mp=115-116. Recrystallization from ether gave pure titled product; wt. 
1.25 g, mp=116.degree.-117.degree.. 
Analysis for: C.sub.22 H.sub.26 N.sub.2 O.sub.3 : Calculated: C, 72.10; H, 
7.15; N, 7.65. Found: C, 72.03; H, 7.02; N, 7.96.