SU453839A3 - METHOD OF OBTAINING PHENYLIMIDAZOLIDINONES - Google Patents

Description

one

This invention relates to a process for the preparation of new compounds that can be used in medicine.

The use of a known exchange reaction, for example, the preparation of tertiary amines from secondary ones, allowed the authors to obtain new compounds with valuable properties.

The described method for the preparation of compounds of general formula I

SNG-SNG

where R is hydrogen, lower alkyl or alkoxy, or a halogen atom; Ri is one of the groups in the meta or para position

- CHR, - Q - A; -CHRa-A; -O-CHR2-CHRi-Q-A,

A Q-straight or branched alkylene chain with 1-4 carbon atoms;

RJ - hydrogen atom, hydroxy group, lower

alkoxy or O — CO — Rs; R2 is a hydrogen atom or a methyl group; Ra and R4 may be the same or different and denote a hydrogen atom, a lower alkyl or alkoxy group, a halogen atom

or a trifluoromethyl group or together a fused aliphatic or aromatic five- or six-membered ring; Rs is a lower alkyl group which may be substituted with a halogen, hydroxy or alkoxy, amino, mono or dialkylamino group; Z is an aromatic ring with 1-2 heteroatoms, to which a benzene ring can be attached too; R is a hydrogen atom or a lower unbranched or branched alkyl, alkenyl, alkynyl, oxyalkyl, dialkylaminoalkyl or aralkyl radical, which means that the amine of the general formula II

II

r E: CH -dH

where R and R have the above meanings, and Ra means one of the groups in the meta or para position

- CHR, - X; - CHR, - Q - X; - O - CHRs - CHR, - Q - X, where RI, R2 and Q are as defined above, and X denotes the HA compound cleaved with hydrogen, HX, for example, a halogen atom, -O-SO2 -alkyl or -O-SO2- aryl, in the presence of a binding agent, predominantly potassium carbonate, sodium or amine, taken in excess, followed by isolation of the desired product as a base, salt and / or diastereoisomers or optical antipodes by known techniques. The following examples where Z means the radical Hts-- N СЯ.- СН. serve to clarify the proposed method. Example 1. Z- / Y-CH.-GH, .N / 28.4 g (0.1 mol) of 2-4-imidazolidinone (2) yl-phenyl-ethylmethyl sulfonate obtained from 2-4-imidazolidiion - (2 ) -yl-phenyl-ethanol and methanesulfonyl chloride in pyridine, is subjected to an exchange decomposition reaction with 17.5 g of N-2-methylphenyl-iierazine in 120 ml of acetonitrile in the presence of 21 g of soda, and is refluxed for 1 h. The compound obtained is isolated in the form of a base, m.p. 195 ° C. The following compounds are obtained in a similar manner (formula I, R is hydrogen; R has the above-mentioned meanings) 4J 1. / 3-O-CH -CHO-H

2.; -SNp-LB (/

Y SgNd

3. / 7-CH-CHrN (he

PRI me R 2.

Sh.

HE

Z - // U (: H-CH, -K (- ()

4.1-4-Imidazolidinone - (2) -yl-phenethyl (4) -3-chlorophenyl piperazine (mp 239 ° C).

5. СНзГГ - «-« О -О

 OH-g

C2H5

T. pl. 234 ° C. 4-Amino acetophenone is reacted with (3-chloroethyl isocyanate and the subsequent treatment with potassium hydroxide is converted to 4 imidazolidinon- {2) -yl-acetophenoia (m.p. 208 ° C). When interacting with 1 mol of bromine in chloroform, co-bromo ketone is obtained (mp 175 ° C). C-CHO-Br 11, 14.2 g of bromoketone in 200 ml of ethiol are mixed slowly and cooled with ice with 2 g of sodium borohydride and then stirred further B for 2 hours and at room temperature. The precipitated sodium bromide is sucked off. 0.5 ml of water and 17.6 g of N-2-methylphenylpiperazine are added to the solution, the initial mixture is left to stand for 10-12 hours, boiled for 2 more hours under reflux and then the above compound is isolated. It has m. Pl. 221-233 ° C. Similarly, the following compounds L-0-CHr CH-CH2- (- {/ f 2. O-cii2-CH-CHo-NQ: 4on CH3 3 is obtained. Z-CH-CH-N K-f CH2 CH 6. (OH) - (ÑСНз Treo- and erythro-form, so pl. 161 ° С 7-, -Сн. 4. т. Pl. 256-257С. 8. Z- (0 - CiI.CH.2- (Ho- Kt pl 171 ° C. 9.1-4-Imidazolidine- (2) -yl-phenyne-4-phenyl-piperazip (mp 210 ° C). 10.1-4-Imidazolidinone- (2) -yl-pheny tyl-4-phenylpiperazine (mp. 218 ° C). 11.1-4-imidazolidinone- (2) -yl-fei-tyl-4-phenylpiperazine (mp 218 ° C). 12.1-4-imidazolidinone - ( 2) -yl-phenytyl-4-phenylpiperazine (mp 218 ° C). 13.1-4-Imidazolidinone - (2) -yl-phene 4- (2-hypolyl) piperazine (mp 187 ° C ) .14.1-4-Imidazolidinone - (2) -pl-phene 4- (2-pyridyl) -piper azip (mp. 200 ° C). 15.1- {4- 3 - Methyl pmidazolidinone- (2) phenethyl} 4- (2-methylfepyl) piperazine (t 196 ° C). 16.1- {4-3 - n- Butylimidazolidinop - (2) yl - fevethyl} -4- (2-methylphenyl) -piperazine (mp. 283 ° C). 17.1- {1-4-Imidazolidinop- (2) -pl-phenyl 1-acetyloxepethyl} - 4 - (2 - methylphenyl) - piperazip (mp: 310 ° C.). 18.1- {1-4-Imidazolidinone - (2) -yl-phenyl 1-methylcarbamoyloxyethyl} - 4- (2-methyl-disppl) -piperazine ( t. square 169 ° C). 19. 1- {1-4-Imidazolidinone - (2) -yl-phenyl 1-ethoxyethyl} -4- (2-methylphenyl) -piperazine. The compounds of formula I listed in the table are prepared analogously. 20. Methylsulfonate-1 - - benzylpmidazolidinone- (2) -yl - phenethyl} -4- (2-methylfeNIL-) piperazine (mp. 194-195 ° C). 21. Dihydrochloride 1 - {4- 3- (2-dimethylamio-ethyl) -imidazolidinone- (2) -yl-phenethyl} -4- (2-methylphenyl) -pper rasine (mp. 308 ° C, decomposition). 22. Dihydrochloride 1- {4- 3- (3-dimethylaminopropyl) - imidazolidinium- (2) -yl-phenethyl} 4- (2-methylphenyl) -piperazine (mp. 309 ° C, decomposition). 23.Hydrochloride (3-ethylimidazolidinon- (2) -phenethyl-4- (2-methylphenyl) -piperazine (m.p. 286 ° C). 24.Hydrochloride 1-4- (3-allylimidazolidnon- (2) -yl -phenethyl-4- (2-methylphenyl) -piperazine (mp. 287 ° C., decomposition). 25. Methyl sulfonate (3-propargylimimidazolidinon- (2) -yl) phenethyl-4-phenyl-pinperazine (mp. 232 233 ° C). 26. Sulfate (4-imidazolidinone (2) -ylphenl) - 1-n-butylcarbamonloxy-ethyl-4- (2-methylphenyl) piperazine (mp. 127 ° C, decomposition).

Compounds of formula 1 (R-hydrogen)

Acid (t. Pl. Or dot

decomposition of salt), so pl. base ° C

t.-CCH.

Cohs

-9

/ 7 - () 2СНз

fl - Sheaf-CH2-N (L

A-CCH. N - Q

Cl

(CHo) -N (K-VCl

ui- (CH2)

/ hco%),

SNS

ON- /

/ R-CHP-CH-B

ff- (

CH,

 - () s-: m (

CHgSOsH (209), 180-181

DDS (211), 195

CHjSOsH (191), 223

DZZZOZN (263-265)

DTHRAL (241)

DTHRAL (271)

DTHRAL (216-217)

HCI (299-301)

DTHZ (325)

DZZZOZN (269-271)

Compounds of formula 1 (R-hydrogen)

5H .- (H2) 2-1t (

p- - (C; H2)

(eH2) 2-k (

ten

Continuation

Acid (t. Pl, or point

decomposition of salt), so pl. base ° C

HCI (278-280)

g. - ./

CHjSOsH (235-236)

DTHRAL (295-298)

-Ch

DONZZODN (255-256)

.0-CCH2)

R- (g O L-0- ()

CHjSOjH (175)

SNS

DTHRAL (202)

OS4N9

SNZZOZN (211), 152

C1b

CHgSOsH (248-250)

- CH-N () - / L- CH3

I / Y- / o

3sn.

DZZZOZN (236-238)

Compounds of Formula 1 (H-Hydrogen)

- Sn Sn-to {to- / VcHg

1, - / Y /

USI

 sn, -

Acid (t. Pl. Or dot

decomposition of salt), so pl. bases, C

CHsSOjH (300-301)

DTHRAL (218)

DZZZOZN (275-279)

 SYT- CH-N

N /

BUT

JOffl,

™ -%

WtiH,

SN.-SNG Invention

1. Method for the preparation of phebilimidazolidinones of formula I

about

sn, -sn

where R is hydrogen, lower alkyl or alkoxy, or a halogen atom;

R is one of the groups in the meta or para position

- CHR, - Q A; - SNNz-A; -O-CHNg-CHRi-Q-A,

where a means radical

DTHRAL (270)

256-257

N-Z

OR

Q is an unbranched or branched alkylene chain with 1-4 carbon atoms; Ri is a hydrogen atom, hydroxy group, lower alkoxy group, or O — CO — Rs group; R2 is a hydrogen atom or a methyl group; Rs and R4 can

be the same or different and mean a hydrogen atom, a lower alkyl or alkoxy group, a halogen atom or a trifluoromethyl group or together a fused aliphatic or aromatic five-

or six-membered ring; Rs is a lower alkyl group which may be substituted with a halogen, hydroxy or alkoxy amino, mono or dialkylamino group; Z-aromatic ring with 1-2 heteroatoms, to which a benzene ring can also be attached; R is a hydrogen atom or a lower branched or branched alkyl, alkenyl, alkynyl, hydroxyalkyl, dinakylaminoalkyl or aralkyl radical, characterized in that the amine of the general formula II where A is as defined above, is reacted with a compound of the general formula III 9-to-7 where R and R is as defined above, and Ra is one of the groups in the meta or para position -CHR, -X; -GHR, -Q-X; - O - CHR, - CHR. - Q - X, where RI, R2 and Q are as defined above, and X denotes the HA compound cleaved with hydrogen, HX, for example, a halogen atom, -O-S02 -alkyl or -O-SOj-aryl, in the presence of a binding agent , followed by isolation of the target product in the form of a base, salt and / or diastereoisomers or optical antipodes by known methods. 2. A method according to claim 1, characterized in that sodium, potassium carbonate or amine carbonate taken in excess is used as the binding agent.