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Патент USA US3092643

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United States
3,002,033
atent
Patented June 4, 1963
1
2
ranging from about 0° C. to about 100° C. For con
venience, it is preferred to carry out the reaction in a
solvent which will not enter into the reaction under the
3,092,633
ZK-ACYLATED 2,3-DIHYDRG-1H-PYRROLG
[3,4-c1PYRiDINES
conditions employed. Solvents which may be used are,
Shreekrishna M. Gadekar, Vailey Cottage, and James R.
Vaughan, lira, New City, N.Y., and Selby B. Davis,
Greenwich, Conn, assignors to American Cyanamid
Company, New York, N.Y., a corporation of Maine
No Drawing. Filed Mar. 14, 1961, Ser. No. 95,509
4 Ciairns. (Cl. 260-295)
This invention relates to certain 2-acylated 2,3-dihydro
1H-pyrrolo[3,4~c]pyridines and, more particularly, is con
cerned with novel compounds which may be represented
for example, benzene, toluene, tetrahydrofuran, chloro
form, and the like. An acid acceptor such as an alkali
metal hydroxide, pyridine, or triethylamine may also be
employed.
The interaction of an appropriate 2,3-dihydro~1I-I
10 pyrrolo[3,4-c]pyridine with an appropriate a,?-unsat1r
rated alkanoic anhydride may be carried out at tem
peratures ranging from about 50° C. to about 100° C.
.Solvents which may be used are, for example, chloro
by the following general formula:
form, toluene, tetrahydrofuran, and the like.
15
The amidation of the lower alkyl esters of the appro
priate a?-UIlSatHIEited alkanoic acids with an appropriate
2,3-dihydroalH-pyrrolo[3,4-cJpyridine may be brought
about under conditions well known in the art.
The invention will be described in greater detail in
conjunction with the following speci?c examples.
wherein ‘R1 is hydrogen or a methyl radical; R2 is hydro
gen or a halogen, hydroxy, lower alkoxy, amino or sub
stituted amino radical; and R3 and R4 are each hydro
gen or a lower .alkyl radical. Suitable lower alkyl radi 25
cals are methyl, ethyl, propyl and isopropyl.
The organic bases of this invention form non-toxic,
acid-addition salts with a variety of organic and inorganic
salt-forming reagents. Thus, acid-addition salts, formed
EXAMPLE 1
6-Methyl-7-Chloro-2-Tigl0yl-2,3-Dihydro-l H-
Pyrrolo [3,4-0] Pyridine
In 175 ml. of 1N sodium hydroxide was dissolved 9.5
g. (0.04 mole) of 6-methyl-7-chloro-2,3-dihydro-1H-pyr
rolo[3,4ac]pyridine dihydrochlonide and 4.7 g. (0.04
mole) of tigloyl chloride. The resulting solution was
by admixture of the organic free base with an acid, suit 30 stirred at room temperature for two hours. The product,
which had precipitated from the aqueous solution, was
ably in a neutral solvent, are formed with such acids as
removed by ?ltration and recrystallized from aqueous
sulfuric, phosphoric, hydrochloric, hydrobromic, sul
ethanol. There was thus obtained 5.2 g. of 6-methyl-7
famic, citric, lactic, malic, succinic, tartaric, acetic, ben
chloro - 2~tigloyl-2,3-dihydro-lH-pyrrolo-[3,4-c] pyridine,
zoic, gluconic, ascorbic and related acids. For purposes
of this invention the free bases are equivalent to their non 35 M.P. 133—‘l35° C.
toxic acid-addition salts.
EXAMPLE 2
The novel compounds of the present invention are, in
6-Methyl-7-Chlor0-2-(
a-Ethylcrotonyl) -2,3-Dihy
general, white crystalline solids, somewhat soluble in
dry-1 H-Pyrrol0 [3,4-c] Pyridine
polar solvents such as water, methanol, ethanol, acetone,
dimethylformarnide and the like; but relatively insoluble 40
in non-polar solvents such as ether, benzene, petroleum
ether, methylene chloride and the like.
The novel compounds of the present invention are
‘In 100 ml. of 1N sodium hydroxide was dissolved 4.9
g. (0.020 mole) of 6-methyl-7-chloro-2,3-dihydro~1H
pyrrolo[3,4-c]pyridine dihydrochloride and 3.0 g. (0.022
mole) of a-ethylcrotonyl chloride. The resulting solu
valuable tranquillizing agents of low toxicity. They are
tion was stirred at room temperature for two hours. The
selective depressants of the central nervous system and
may be administered parenterally or orally. When so ad
ministered to mammals, they have been found to be use
ful in amounts ranging from about 1 to about 50 milli
product, which had precipitated from the aqueous solu
tion, was removed by ?ltration and recrystallized from
grams per kilogram of body weight.
lH-pyrrolo[3,4-c]pyridine, M.P. 120-12l° C.
The novel compounds of the present invention may
be readily prepared by the interaction of an appropriate
2,3-dihydro-lI-Lpyrrolo[3,4-c]pyridine with a reactive
derivative of an appropriate a,B-unsaturated alkanoic
acid such as the acid halide, acid anhydride or ester.
The intermediate 2,3-dihydro-1H-pyrrolo[3,4-c] pyridines
corresponding to the following general formula:
R:
an
N
aqueous ethanol.
There was thus obtained 3.6 g. of 6
methyl - 7 - chloro - 2 - (a - ethylcrotonyl) - 2,3 - dihydro
EXAMPLE 3
6-Methyl-7-Amin0-2-( a-Ethylcrotonyl) -2,3-Dihydr0
I H-Pyrr0lo [3,4-0] Pyridine
In 100 ml. of 1N sodium hydroxide was dissolved 5.0
g. (0.0225 mole) of 6-methyl-7-amino-2,3-dihydro-1H
pyrrolo[3;4-c]pyridine dihydrochloride and 3.0 g. (0.0225
mole) of u-ethylcrotonyl chloride. The resulting solu
tion was stirred at room temperature for two hours.
NH
wherein R1 is hydrogen or methyl, and R2 is hydrogen,
halogen, hydroxy, lower alkoxy, amino or substituted
amino are known in the art and readily prepared by stand 65
ard procedures. Similarly, the intermediate acid halides,
acid anhydrides and esters of the appropriate ups-unsatu
rated alkanoic acids are also known in the art and readily
prepared by conventional methods.
The interaction of an appropriate 2,3l-dihydro-1H 70
pyrrolo[3,4-c]pyridine with an appropriate a,?~unsatu
rated alkanoyl halide may be carried out at temperatures
The product, which had precipitated from the aqueous
solution, was removed by ?ltration and recrystallized
from aqueous ethanol. There Was thus obtained 2.75 g.
of 6-methyl-7-amino-2-(a-ethylcrotonyl)-2,3-dihydro-1H
pyrrolo[3,4~c]pyridine, M.P. 2r28-230° C. (dec.).
We claim:
1. A member of the class consisting of amides having
the formula:
3,092,333
3
wherein R1 is selected from the group consisting of hydro
gen and methyl, R2 is selected from the group consisting
‘of hydrogen, halogen, hydroxy, lower alkoxy, and amino,
and R3 and R4 are each selected from the group consist
ing of hydrogen and lower alkyl, and the non-toxic acid
addition salts thereof.
‘
.2. The compound 6-methyl-7-chloro-2-tigloyl~2,3-dihy
dro-lH-pyrrolo[3,4-c1pyridine.
3. The compound 6-methyl - 7 - chloro-2~(a-ethylcro
ton-yl) -2,3 -dihydro-1H-pyrro1o [3,4-0] pyridine.
4. The ‘compound 6 - methyl - 7 -amix1o-2-(a-ethylcro
tonyl) -2,3 -dihydro- 1H-pyrrolo[ 3,4-c] pyridine.
4
References Cited in the ?le of this patent
UNITED STATES PATENTS
2,767,191
Wright ______________ __ Oct. 16, 1956
OTHER REFERENCES
Wright et al.: I.A.C.S., volume 79, pages 2199-2203
(1957).
Noller: “Chemistry of Organic Compounds,” 2nd edi
10 tion, pages 244-5 (1957) (Saunders).
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