Method of producing buspiron

专利摘要:
Novel spiro-quaternary ammonium halides are disclosed. The new compounds are particularly valuable as intermediates in preparation of N-(2-pyrimidinyl)piperazinylalkyl derivatives of azaspiroalkanediones such as the psychopharmacologic agent 8-[4-[4-(2-pyrimidinyl)-1-piperazinyl]butyl]-8-azaspiro[4.5]decane-7,9 -dione.
公开号:SU1342420A3
申请号:SU833562184
申请日:1983-03-09
公开日:1987-09-30
发明作者:С.Симмз Джек
申请人:Бристоль Мейерз Компани (Фирма)；
IPC主号:

专利说明:

1342420
The invention relates to a method
the preparation of buspirone, a biologically active compound, which is used in medicine.
The purpose of the invention is to increase the yield, simplify the process and expand the raw material base.
Thus, the application of the proposed method allows to increase the yield of the target product up to 80% (67% in the known method), simplify the process, reduce the number of stages, and get a higher degree
Found,%: C 60.07; H 7.72; N 16.74; C1 8.27.
The reaction is in dimethylformamide. A mixture of 3,3-tetramethylene glutaramide (16.7 g; 0.1 mol), 8- (2-pyrimidinyl) -8-aza-5-azoniaspiro 4, 5 decan bromide (29.9 g, 0.1 mol) and Potassium carbonate (16.6 g, 0.12 mol) in 190 ml of dimethylIQ formamide is incubated for 24 hours at 150-155 and then evaporated to dryness under reduced pressure. The resulting solid residue is treated with 90 ml of water, converted into 10% vegetation, thus expanding the raw material igor the hydrochloric acid and filtering out the base as the starting material. The acidic filtrate is treated with a halogen derivative of 8-alkali treatment with 10% aqueous (2-pyrimidinyl) -8-aza-5-azoniospirometry sodium hydroxide solution, fallen 4.53-decane and 3,3-tetramethylene glutar in the precipitate free base , filter-amide. 20, dry, get 8- 4- 4 Example 1. 4- (2-11 yyrimyl- (2-pyramidinyl) -1-piperazinsh1 butyl-dynyl) -1-piperazinyl-butyl-8-azas-8 -asaspiro-4,5-decane-7,9-dione. Pyro-4.53-decane-7,9-dione (buspirone) Following this procedure,
but using 8- (2-pyrimidinyl) -8-aza-25 5-azoniaspiro-4,5-decan chloride monohydrate (27.3 g, 0.1 mol) instead of the corresponding quaternary base bromide, the designated compound is obtained as a free base. N: N-CH2 (CH CH2-N (N. J
 ABOUT
I Reaction in n-butanol. A mixture of 3,3-tetramethylene glutaramide (7.5 g, 0.045 mol), 8- (2-pyrimidinyl) -8-aza-30 nor in 80% yield, m.p. 100 C. 5-azoniaspiro-4.53-decane bromide (15.4 g, 0.045 mol), potassium carbonate (6.2 g, 0.045 mol) in 250 ml of n-butanol is boiled for 21 hours, filtered. | and evaporated to dryness. Water is added to the residue, and the mixture is alkalinized with an aqueous solution of sodium hydroxide. The insoluble residues are combined and washed with water, after which they are obtained

权利要求:
Claims (1)
[1]
Invention Formula
The method of obtaining buspirone formula I
ABOUT
sn2 (sn.5). () s-h D)
 ABOUT
11.5 g (yield 66.5%) (2-pyri-40 by reacting equimolar midinyl) -1-piperazinyl-butyl 8-aza-spiro-4,5-decane-7,9-dione as a free base with tpl.90-98 C.
quantities. spiroglutaramide and a pyrimidinyl piperazine derivative in a polar organic solvent at boiling, characterized by the fact that, in order to increase the yield, simplify the process and expand the raw material base, 3,3-tetramethylene glutamide is used as a spiroglutaramide, held in isopropanol and treated with concentrated hydrochloric acid, forms a hydrochloric acid salt. Crystallization from isopropanol leads to abrasiveness. spiroglutaramide and a pyrimidinyl piperazine derivative in a polar organic solvent at boiling, characterized by the fact that in order to increase the yield, simplify the process and expand the raw material base, 3,3-tetramethylene glutamide is used as the spiroglutaramide salt- 50 action with halogen-8 (2-pyrimidinyl) -8-aza-5-azoniospiro- 4, dean of the formula, -N
acid salt (2-pyrimidinyl) - 1-piperazinyl butyl-8-azaspiro-4,3-dekane-7,9-dione.
Calculated,%: C 59.77; H 7.65; N 16.60; C1 8.40
Ci, H3, NsO ,, - HCl
LOST ORDER 4447/58
nor with the yield of 80%, so pl. 100 C.
Invention Formula
The method of obtaining buspirone formula I
ABOUT
sn2 (sn.5). () s-h D)
 ABOUT
by interacting equimolar
by interacting equimolar
quantities. spiroglutaramide and a pyrimidinyl piperazine derivative in a polar organic solvent at boiling, characterized in that, in order to increase the yield, simplify the process and expand the raw material base, 3,3-tetramethylene glutamide is used as the spiroglutaramide, which is reacted with the halo derivative. ) -8-aza-5-azoniospirocan of the formula, -N
Present the presence of an alkaline catalyst. Circulation 371 Subscription
Poyzv.-poly. pr-tie, Uzhgorod, st. Project, 4

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法律状态:

优先权:

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申请号 | 申请日 | 专利标题

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US06/197,416|US4351939A|1980-10-16|1980-10-16|Spiro-quaternary ammonium halides and N-piperazinylalkylazaspiroalkanedione process|

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