Method of preparing thieno(2,3-c) or thieno-(3,2-c)-pyridines

专利摘要:

公开号:SU728717A3
申请号:SU782627501
申请日:1978-06-21
公开日:1980-04-15
发明作者:Маффран Жан-Пьер
申请人:Паркор (Фирма)；
IPC主号:

专利说明:

R carboxyl group, aryl, in the medium of an organic solvent in the presence of an acceptor of hydrohalic acid and get: with co-f-dinakie formula IV
Kg Ovz
BI
where R, R, RjijRj - have indicated
meanings
which is boiled for 3-6 hours in an organic solvent medium, for example dioxane, in the presence of acid areHTaL J.
This method, taking into account also the preparation of the starting compounds, is a multistep (5 stages), which allows to obtain the target product with a yield not higher than 20%.
The aim of the invention is to increase the yield of the target product.
The goal is achieved by the method of obtaining thieno 2, thieno 3, 2-pyridines of formula U.
k
U / IU
-
where R is hydrogen or carboxyl
Group,
a distinctive feature of which is that the compounds of formula VI
is:
-zs
“L
where X is NH
Y - CH COOH, Z - CHN ,,
znon
or X - CH COOH, y - NH,
Z is snon, z is sn,
subjected to interaction with nitrous acid, followed by treatment of the corresponding nitrosoamine hydrochloric or trifluoroacetic acid, thus obtained,. or hydrated alkaline oxide.
It is advisable for nitrosation of nitrous acid to be obtained directly in the reaction zone from alkali metal nitrite and hydrochloric acid.
In this case, it is desirable to slowly add an aqueous solution of alkali metal nitrite to the hydro-acidic solution of compound X, first, followed by aging the reaction mixture for several hours at room temperature.
When treating a nitrosoamine to obtain a compound of the formula, where R is hydrogen, pure trifluoroacetic
acid reaction. proceeds ;-) k-oter. ™ h n o g in with l o u c e n i :: parasol o lu acid; try heating the reaction mixture to temperature: reaction.
Initial compounds form: / ul; N; they are recieved in 3 au mode and from in and out (.
HE
.ClDOH
AI;
one
uflV 3JK;
R
011
with formaldehyde acid,
PREDUL; g ae /.y and p ps about Obtaining a target from 32-97%.
PRI me R I, Ps. Radiation of carbsi-5-hydroxy - 4-nitroes - 6-tetrahyd1:, o-4, 5, b, 7-tio-2, .3-e 1 -g; irid; And; -: a,
To a suspension of 20 g (O, - 1 mol / k-z. Rboxy-5-hydroxy-4-tetra idro-4., 5, 6, 7b n
) oh
M
hydrochloric acid
peremetannoy with PP1 .0 with the power magnetic stirrer
. at
, - „,„ - 3 is added dropwise 200
: C.% 1: about 1 g of an aqueous solution of Katsi nitrite (2.9 eq.) And stirring the mixture at room temperature for 3 hours. The reaction mixture remains keodons / Ron during the whole process. Nitrogen-lary lars are observed. A precipitate from Li Litr 1Ey; :: ayut is washed with water and dried: s: -lkoum, get kris / al.g: b :: Z17 sog
NIN 100 and
Example 2, Og; Uz ;; :
cedur in the same way, measure 1, п о j: at tea t to ar side b -nitrozo-5-tetrahydro-4, 3
. b 3,2-CJ-pyridine, the product softening
Example 3 P 3,2 Read to a.
A solution of 24 g nitroscopy
Risvodnogo, - received in 2 O O cm 6
n .. SALT KIS; in tkcheklz warm with
Fueled gas ...
bath (paros. Pus, ne ohla; de reaction mixture of brown csc-h .-;:: .yrgl l watered with caustic natrium to -jKc-psr-icyyut methlenes chloride. M, Cc-g- the extracts are washed with soda., uyoug: eaet over sulfaano. three., about two changes change. on black, and then filtered MSC-s tal-: and evaporated to dryness. After ..-. After evaporation of the product, I get 6, 5 g (total yield is blown: and on the initial compound fo; d-1LP:; - L 43%) type 3 f 2 s .1 - n and G; go to;;: and the second crystal is molded prn .wne.The temperature is - -.- to- --- -n.
Example 4. Carrying out the procedure in the manner described in Example 3, using as the starting material the nitrosated compound prepared according to Example 1, thieno 2, 3rd e-pyridine is obtained with a yield of 47%. Temperature of fuse softening С
Example. 5. Preparation of carboxy-5-thieno 2, 3-pyridine.
A pre-mixed roaster of 10 g (0.044 mol) of the nitrosated derivative obtained in Example 1 in 20 cm of ethanol and 60 cm of 20% sodium hydroxide is refluxed for 2 hours. After cooling and addition of ethanol, a precipitate is formed, which is filtered, washed with ethanol and then with diethyl ether and dried. The resulting sodium salt, pl. , yield 4.7 g (60%) / treated with 23 cm (1 eq.) 1 n. hydrochloric acid. The salt is dissolved, and then re-precipitation is observed. Recrystallization of the product takes place immediately after the addition of 27 cm of water. Obtain 2.5 g (32%) of pinkish crystals of the target product, so pl. 246 ° C.
Example 6. Carrying out the procedure in the same manner as in Example 5, using as the starting product the nitrosated derivative corresponding to Example 2, we obtain carbokei-6-thieno 3, 2-ε-pyridine, which is pinkish crystals, c. square 212 ° C. The yield of this product is 84%.
Example 7. Preparation of thieno 3,2-pyridine.
To 55 cm of trifluoroacetic acid mixed at room temperature, 1J, 4 g of the starting compound of formula V, added to Example 2, are added as a separate temperature. The temperature is increased from 19 to 34 ° C, and a reddish vapor is released. The temperature of the reaction mixture is reduced to room temperature.
this mixture is then added to ice, triturated by addition of ammonium hydroxide and extracted with diisopropyl ether. Organic ecological extracts are washed with water, dried over sodium sulfate and evaporated to dryness. After distillation in vacuo, the resulting liquid evaporating the product gives 3.8 g (56%) of thieno 3,2-e-pyridine.

权利要求:
Claims (2)
[1]
Invention Formula
, 1. Methods for producing thieno 2, thieno 3,2-e-pyridines of the formula
Yes
,
I 1 jl
tint /
 ,
where R is hydrogen or carboxyl
Group,
characterized in that, in order to increase the yield of the target product, the compound of the formula
6if
GT V
where X is NH,
five
Y - CH SOOH
[2]
2. - CHg,
Z is CHQH, or X is CH CH,
Y - NH,
0
Z - SNSON
Z CH,
they are subjected to interaction with e-acid with e with the subsequent treatment of the corresponding educt-corresponding nitrosoamine with hydrochloric or trifluoroacetic acid, or with alkali metal oxide hydrate.
2. Solvents prepared according to claim 1, which differs from the fact that nitric acid is obtained directly in the reaction zone from alkali metal nitrite and eolic acid.
Sources of information taken into account in the examination
1.J.P.Maffrand Nouvelles synt5 heses de thieno 3,2-c u thieno 2, 3- pyridines J. of Heteroeyclic, Chemistry, 13, 1976, p. 1347.
2.Patent of France No. 2312498, cl. C 07 D 495/04, published 1976
0 (prototype).

类似技术:

---

公开号 | 公开日 | 专利标题

---

SU728717A3|1980-04-15|Method of preparing thieno| or thieno-|-pyridines

---

US4369142A|1983-01-18|Process for producing N-phosphonomethylglycine

---

US4486358A|1984-12-04|Process for producing N-phosphonomethylglycine

---

US3553224A|1971-01-05|1|-pyridine-sulfonates

---

SU453830A3|1974-12-15|METHOD OF OBTAINING ACCORDINGLY FIXED PHENACETHILGUANIDINE

---

US3036087A|1962-05-22|Process for the preparation of phosphocreatine and/or phosphocreatinine

---

RU2248353C2|2005-03-20|Method for preparing 3-methyl-1,2,4-triazolyl-5-thioacetate morpholinium

---

SU1690543A3|1991-11-07|Method for preparation of pyridine-2,3-dicarboxylic acid derivatives or theirs n-oxides

---

SU865787A1|1981-09-23|Method of producing yttrium orthophosphate dihydrate

---

KR100343232B1|2002-07-10|Crystal pamidronate disodium hydrates and process for preparing them

---

SU591150A3|1978-01-30|Method of preparing nitroimidazolyltriazolopyridazine derivatives or salts thereof

---

US4534904A|1985-08-13|Process for producing N-phosphonomethylglycine

---

SU1742207A1|1992-06-23|Method for preparation of copper-ammonium phosphate hydrate

---

US4841092A|1989-06-20|Preparation of tris|amine

---

SU667546A1|1979-06-15|Method of producing 3,3'-dichloro-4,4'-diaminodiphenyl methane

---

SU1168562A1|1985-07-23|Method of obtaining 4-|pyridilmethane

---

US2190167A|1940-02-13|Process for production of ascorbic acid

---

SU1608114A1|1990-11-23|Method of producing manganese hydrophosphate monohydrate

---

CA2934535A1|2015-06-25|Large scale manufacture of 2,4-pyrimidinediamines and intermediates

---

SU1558908A1|1990-04-23|Method of obtaining 10-methyl-3-|acridinone

---

SU1664790A1|1991-07-23|Method for obtaining nъ-alkyl|-nъ-nitroso-benzamiderazones

---

SU1735269A1|1992-05-23|Method for producing lead acetate

---

SU232268A1|METHOD OF OBTAINING 6-ALKYLPYRIMIDO-

---

SU514836A1|1976-05-25|The method of obtaining derivatives 12 aminoindolo | quinazolines

---

SU1664785A1|1991-07-23|Method of producing lead acetate

同族专利:

---

公开号 | 公开日

---

DK147827B|1984-12-17|

---

YU135878A|1982-10-31|

---

PL113510B1|1980-12-31|

---

JPS549298A|1979-01-24|

---

ZA783051B|1979-06-27|

---

HU178316B|1982-04-28|

---

NO782147L|1978-12-22|

---

GB1584143A|1981-02-04|

---

DD135492A5|1979-05-09|

---

FR2395271B1|1980-04-04|

---

NO149315B|1983-12-19|

---

IT7849919D0|1978-06-19|

---

DE2860164D1|1980-12-18|

---

IE781023L|1978-12-21|

---

AU3725578A|1980-01-03|

---

YU40709B|1986-04-30|

---

AU515505B2|1981-04-09|

---

CA1074800A|1980-04-01|

---

AT362372B|1981-05-11|

---

PL207770A1|1979-05-07|

---

NO149315C|1984-03-28|

---

GR64843B|1980-06-04|

---

DK147827C|1985-06-10|

---

LU79787A1|1978-11-28|

---

NZ187625A|1980-11-28|

---

EP0000301A1|1979-01-10|

---

IL54780D0|1978-07-31|

---

FI63236B|1983-01-31|

---

IE47055B1|1983-12-14|

---

FI781900A|1978-12-22|

---

FR2395271A1|1979-01-19|

---

US4161599A|1979-07-17|

---

CH635588A5|1983-04-15|

---

JPS6230192B2|1987-07-01|

---

IT1105427B|1985-11-04|

---

EP0000301B1|1980-09-17|

---

IL54780A|1981-01-30|

---

ES469703A1|1978-12-16|

---

FI63236C|1983-05-10|

---

MX5020E|1983-02-22|

---

ATA337978A|1980-10-15|

---

AR216515A1|1979-12-28|

---

BE868272A|1978-12-20|

---

PH17024A|1984-05-11|

---

PT68182A|1978-07-01|

---

DK266978A|1978-12-22|

引用文献:

---

公开号 | 申请日 | 公开日 | 申请人 | 专利标题

---

---

US3997545A|1973-07-23|1976-12-14|Takeda Chemical Industries, Ltd.|Thienopyridine-carboxylic acid derivatives|

---

FR2263745B1|1974-03-12|1977-12-02|Roussel Uclaf|

---

FR2278683B1|1974-07-16|1978-07-13|Parcor|

---

FR2312247B1|1975-05-30|1978-08-18|Parcor|

---

FR2312498B1|1975-05-30|1978-03-17|Parcor|

---

FR2315274B1|1975-06-27|1979-08-10|Parcor|

---

FR2345150B2|1975-08-06|1979-05-25|Centre Etd Ind Pharma|BE816390A|1973-06-15|1974-12-16|Vinyl or ethynyl-substd. mercapto-methyl pyridines - for treatment of rheumatoid arthritis and inflammatory troubles|

---

JPH0518623B2|1984-09-17|1993-03-12|Dainippon Ink & Chemicals|

---

US5962490A|1987-09-25|1999-10-05|Texas Biotechnology Corporation|Thienyl-, furyl- and pyrrolyl-sulfonamides and derivatives thereof that modulate the activity of endothelin|

---

CA2182090A1|1994-02-02|1995-08-10|William Joseph Hornback|Hiv protease inhibitors and intermediates|

---

US5958905A|1996-03-26|1999-09-28|Texas Biotechnology Corporation|Phosphoramidates, phosphinic amides and related compounds and the use thereof to modulate the activity of endothelin|

---

US5804585A|1996-04-15|1998-09-08|Texas Biotechnology Corporation|Thieno-pyridine sulfonamides derivatives thereof and related compounds that modulate the activity of endothelin|

---

FR2797874B1|1999-08-27|2002-03-29|Adir|NOVEL PYRIDINE DERIVATIVES, THEIR PREPARATION PROCESS AND THE PHARMACEUTICAL COMPOSITIONS CONTAINING THEM|

法律状态:

优先权:

---

申请号 | 申请日 | 专利标题

---

FR7718991A|FR2395271B1|1977-06-21|1977-06-21|

---