GB2078224A - The Preparation of Indolo[2 min ,3 min ;3,4]-pyrido[2,1b]-quinazolin-5-ones - Google Patents
The Preparation of Indolo[2 min ,3 min ;3,4]-pyrido[2,1b]-quinazolin-5-ones Download PDFInfo
- Publication number
- GB2078224A GB2078224A GB8119296A GB8119296A GB2078224A GB 2078224 A GB2078224 A GB 2078224A GB 8119296 A GB8119296 A GB 8119296A GB 8119296 A GB8119296 A GB 8119296A GB 2078224 A GB2078224 A GB 2078224A
- Authority
- GB
- United Kingdom
- Prior art keywords
- acid
- hydrogen atom
- represent
- formula
- methoxy group
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
- C07D471/14—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
Compounds of the formula <IMAGE> (wherein i) R<1>, R<2>, R<3> and R<4> each represents a hydrogen atom and R represents a methoxy, benzyloxy, hydroxy or methoxycarbonyl group; ii) R, R<1> and R<4> each represent a hydrogen atom, R<3> represents a methoxy group and R<2> represents a hydrogen atom or a hydroxy, benzyloxy or methoxy group; iii) R, R<2>, R<3> and R<4> each represent a hydrogen atom and R<1> represents a hydroxy or methoxy group; iv) R represents a methoxy group R<1> and R<4> each represent a hydrogen atom and R<2> and R<3> each represent a methoxy group; v) R, R<1> and R<4> each represent a hydrogen atom and R<2> and R<3> together form a methylenedioxy group; vi) R, R<1>, R<3> and R<4> each represent a hydrogen atom and R<2> represents a methoxy group; vii) R, R<1>, R<2> and R<3> each represent a hydrogen atom and R<4> represents a methoxy group; or viii) R, R<1>, R<2>, R<3> and R<4> each represent a hydrogen atom and the acid addition salts thereof are obtained by the cyclization of 6-phenylhydrazono-6,7,8,9-tetrahydro-11H-pyrido[2,1-b]quinazolin-11-ones or acid addition salts thereof in the presence of a Fischer-indole catalysts. If desired the indolo [2 min ,3 min ;3,4]pyrido[2,1-b]quinazolin-5-ones obtained are converted into acid addition salts. The cyclization is conveniently effected at an elevated temperature and the Fischer-indole catalyst is preferably an acid e.g. an inorganic, organic or Lewis acid. The indolo[2 min ,3 min ;3,4]pyrido[2,1-quinazolin-5-ones possess diuretic activity as well as an activity on respiration and on blood pressure.
Description
SPECIFICATION
A Process for the Preparation of Indolo[2',3';3,4]pyrido[2,1 -b]quinazolin-5- ones and the Acid Addition Salts Thereof
The present invention relates to a process for
the preparation of indolo[2',3';3,4]pyrido[2,1 - b]quinazoline-5-ones and the acid addition salts thereof. Such compounds possess interesting physiological properties.
The indolo[2',3';3,4]pyrido[2,1-b]quinazolin- 5-ones prepared according to the process of the present invention possess the general formula
wherein R, R1, R2, R3 and R4 are as hereinafter defined.
Most of the compounds of general formula I are alkaloids which may be found in plants (J. Am.
Chem. Soc 82, 5187 [1960]; Tetrahedron
Letters 1968, 4865; Phyto-chemistry 11, 1833 [1972]; 12,2521 [1973]; 13,1603 [1974]: 14, 2059 [1975]; 15,1095 [1976]). Compounds of general formula I may be used as diuretics and moreover possess an activity on respiration and blood pressure. The advantageous physiological activity of Rutaecarpine (diuretic, respiration and blood pressure influencing activity) has been reported: (compt. rend. 220, 792 [1945]; 255, 11 52 [1962]; Japan Kokai 77 77.098, Chem.
Abstr. 87, 1 84748a [1977]).
Rutaecarpine, a compound of general formula I in which R, R1, R2, R3 and R4 each represent hydrogen, was isolated in 915 from a plant called
Evodia Rutaecarpa (J. Pharm. Soc. Japan, 405, 1293 [1915] and its structure was determined in the following years (J. Pharm. Soc. Japan, 416, 871 [1916];476,863 [1921];503 1 [1924]; 530, 293 [1926]; 534, 63 [1926]; 543,51 [1927]; 545, 541 [1927]). Rutaecarpine has also been isolated from other plants (J. Am. Chem. Soc 82, 5187 [1960]; Tetrahedron 8, 293 [1960];
Yao Hsueh Hsueh Pao, 13, 265 [1966]; Chem.
Abstr. 65, 3922d [1966]; Yakugaku Zasshi 87, 608 [1967]; Austr. J. Chem. 23, 133 [1970];
Science Record 4,279 [1951]; Chem. Abstr. 46, 11589 [1951]).
Compounds of general formula I have generally been prepared by reacting an appropriately substituted 1 ,2,3,4-tetrahydro-norharman- 1-one or 3,4-dihydro-beta-carboline or derivative thereof with a derivative of anthranilic acid (J.
Am. Chem. Soc. 82, 5187 [1960]; Ann. Chim.
Rome 53, 224 [1963]; Izv. Akad. Nauk Arm. SSR,
Khim. Nauki 14,393 [1961]; 17,230 [1964];
Phytochemistry 11, 1833 [1972]; 13,1603 [1974]; J. Chem. Soc. Perkin 1. 1977, 2347; Japanese Kokai Tokkyo Koho 78,147,096) and after long processing, optionally including chromatography, compounds of the general formula I are obtained in a yield of less than 50%.
A major disadvantage of the aforementioned process is that tryptamine or a substituted derivative thereof has to be used when preparing 1,2,3 ,4-tetrahydronorharman- l-ones or 3,4dihydro-beta-carboline-derivatives for use as a starting material. The synthesis of Rutaecarpine has been reported using several different processes: (J. Pharm. Soc. Japan 543, 51 [1927];
J. Chem. Soc. 1927, 1710; Angew. Chem. 50, 779 [1937]; J. Pharm. Soc. Formosa 51,2 [1938]; J. Pharm. Soc. Japan, 60, 311 [1940];
Annalen 623, 166 [1959]; Izv. Akad. Nauk. Arm.
SSR, Khim. Nauki 14,393 [1961]; Acta Chim. 72, 221 [1972]; Heterocycles 4, 1487 [1976]; J. Am.
Chem. Soc. 99, 2306 [1977]) but one common feature of these processes is that tryptamine is used as starting material and the yield obtained by these processes is at best average. The best yield (80%) was achieved by reacting anthranilic acid with 3,4-dihydro-P-carboline in the presence of thionyl chloride (Heterocycles 4, 23 [1 976]; J.
Am. Chem. Soc. 98, 6186 [1976] but as described above 3,4-d ihydro-,l-carboline is prepared from tryptamine and a multi-step process is involved.
The present invention is based on the discovery that compounds of formula I may be prepared in good yield and with a high degree of purity by reaction hereinafter referred to as cyclization, of a 6-phenylhydrazono-6,7,8,9 tetrahydro-11 H-pyrido-[2, 1 -b]quinazolin-1 1 one or an acid addition salt thereof in the presence of
a Fischer-indole catalyst for example under the
conditions of a Fischer-indole synthesis (Chem.
Rev. 63, 373 [1963]; 69, 230 [1969];
Tetrahedron 36 161 [1980].
Thus according to the present invention there
is provided a process for the preparation of
compounds of the general formula:
(wherein
i) R', R2, R3 and R4 each represents a hydrogen atom and R represents a methoxy, benzyloxy, hydroxy or methoxycarbonyl group;
ii) R, R1 and R4 each represent a hydrogen atom, R3 represents a methoxy group and R2 represents a hydrogen atom or a hydroxy, benzyloxy or methoxy group;
iii) R, R2, R3 and R4 each represent a hydrogen atom and R1 represents a hydroxy or methoxy group;
iv) R represents a methoxy group, R' and R4 each represent a hydrogen atom and R2 and R3 each represent a methoxy group;
v) R, R' and R4 each represent a hydrogen atom and R2 and R3 together form a methylenedioxy group;
vi) R, R1, R3 and R4 each represent a hydrogen atom and R2 represents a methoxy group;;
vii) R, R1, R2 and R3 each represent a hydrogen atom and R4 represents methoxy group; or
viii) R, R1, R2, R3 and R4 each represent a hydrogen atom) and the acid addition salts thereof, which process comprises the cyclisation of a compound of the formula:
(wherein R, R', R2, R3 and R4 are as herein defined) or an acid addition salt thereof in the presence of a Fischer-indole catalyst, and if desired converting a compound of formula I obtained into an acid addition salt thereof.
The term "Fischer-indole catalyst" as used herein relates to catalysts which may for example be used in the Fischer-indole synthesis and includes acids such as for example inorganic acids, organic acids and/or Lewis acids.
The cyclization is preferably effected at an elevated temperature up to 2200 C, for example 30 to 2200 C.
The cyclization is also conveniently effected in the presence of a solvent such as an alkanol e.g.
methanol or ethanol, water, an aromatic hydrocarbon e.g. benzene, toluene or xylene, an ether e.g. diethyl ether, dioxan or tetrahydrofuran or a halogenated hydrocarbon e.g. chloroform, carbon tetrachloride or chlorobenzene etc.
Inorganic acids for use in the present invention advantageously include hydrogen chloride, hydrogen bromide, hydrogen iodide, sulphuric acid, phosphoric acid, but especially polyphosphoric acid. Organic acids for use in the present invention advantageously include aliphatic carboxylic acids e.g. alkanoic acids e.g.
formic acid, acetic acid, oxalic acid, propionic acid or capronic acid; and aromatic hydroxy derivatives e.g. phenol. Lewis acids for use in the present invention advantageously include metal halides, e.g. zince chloride, zinc bromide, aluminium chloride, copper chloride, copper bromide, nickel chloride, platinum chloride, cobalt chloride, stannous chloride, beryllium chloride or magnesium chloride; boron trifluoride and amine salts e.g. aniline hydrochloride, aliphatic carboxylic acid halides, preferably alkanoyl halides e.g. acetyl chloride or propionyl chloride; Grignard reagents e.g. phenyl magnesium chloride, phenyl magnesium bromide, ethyl magnesium bromide or methyl magnesium iodide; ion exchangers in H form e.g. Amberlite IR-i 20, or metal powder e.g. copper powder, nickel powder or cobalt powder.
The above mentioned Fischer-indole catalysts may preferably be used in admixture. Thus for example the following mixture of catalysts may be used:-- sulphuric acid/aliphatic carboxylic acid e.g. alkanoic acid preferably sulphuric acid/acetic acid; hydrogen halide/aliphatic carboxylic e.g.
alkanoic acid preferably hydrogen chloride/acetic acid or hydrogen bromide/acetic acid; boron trifluoride/aliphatic carboxylic e.g. alkanoic acid preferably boron trifluoride etherate/acetic acid; metal halide/aliphatic carboxylic e.g. alkanoic acid, preferably nickel chloride/acetic acid); and metal halide/hydrogen halide preferably stannous chloride/hydrogen chloride.
The temperature at which the reaction may be performed is conveniently dependent on the catalyst and solvent used.
A particular preferred method according to the invention comprises effecting the cyclization in the presence of polyphosphoric acid, conveniently at a temperature of from 100 to 2200C, preferably 140 to 21 00C, especially 160 to 2000 C. The cyclization is preferably effected in the presence of 5-20 parts by weight of polyphosphoric acid per 1 part by weight of the pyrido-quinazoline of general formula II or acid addition salt thereof. The reaction is preferably performed for from 5 to 120 minutes.
The compound of formula II used in the process of the present invention may conveniently be used in the form of the hydrogen halide salt e.g. the hydrochloride.
The indolo[2',3';3,4]pyrido[2, 1 -b]quinazolin-5- ones of formula I obtained according to the present invention may, if desired be isolated according to conventional techniques, for example by diluting the reaction mixture, cooled, preferably to room temperature, with water and by removing the precipitated crystals e.g. by filtration or centrifugation etc.
The obtained indolo[2',3';3'4jpyrido[2, i-b]- quinazolin-5-ones may if desired, be crystallized
and optionally converted to acid addition salts by
methods known per se. Thus, for example, the
hydrochloride, sulphate; acetate orfumarate salt
may be formed by reaction of the compound of formula I with hydrochloric, sulphuric, acetic or fumaric acid respectively.
The pyrido-quinazolines of general formula Il used as starting materials in the process of the
present invention may be prepared as described
and claimed in our copending patent application filed 23rd June 1981 under the title "6
Hydrazono-pyrido[2,1 -b]-quinazolRn- 1-ones
and the salts thereof, and processes for their
preparation".
Thus the compounds of formula Il may be
prepared by a diazo-coupling reaction., 6,7,8,9 Tetrahydro- 11 H-pyrido[2,1 -b]quinazolin- 11-ones of the general formula
(wherein R1, R2, R3 and R4 are as hereinbefore defined) may thus be reacted with a phenyl diazonium halide, e.g. chloride of the general formula
(wherein R is as hereinbefore defined). The diazocoupling reaction can be carried out by methods known per se, preferably in the presence of aqueous acetic acid. 6,7,8,9-Tetrahydro- 11H- pyrido[2,1-b]-quinazolin-11-ones are known compounds and may be prepared for example from a 2-piperidone derivative and a suitable anthranilic acid derivative (see J. Am. Chem. Soc.
99, 2306 [1977]).
The following Examples are given by way of illustration only.
Example 1
Rutaecarpine
10 g. of 6-Phenyl-hydrazono-6,7,8,9 tetrahydro-11 H-pyrido[2,1 -b]quinazolin-1 1 one hydrochloride are added to 100 g of polyphosphoric acid and heated to 1 800C in portions over a period of 5 minutes. After the addition, the reaction mixture is stirred for 30 minutes at 1 80cC. After cooling, the mixture is diluted with 200 ml. of water and the pH is adjusted to 5 by adding 25 V/W% ammonium hydroxide solution. The precipitated crystals are filtered, washed with water and dried. 8.3 g.
(98%) of Rutaecarpine are obtained which after recrystallization from ethyl acetate melts at 2580C.
Analysis for the formula C,8H13N3O
Calculated:
C 71.67% H 5.68% N 17.59%
Found:
C 71.62% H 5.66% N 17.65%
Example2
Rutaecarpine
10 g. of 6-Phenyl-hydrazono-6,7,8,9 tetrahydro-i 1 H-pyrido[2,1 -b]quinazolin-1 i-one are added to 100 g of polyphosphoric acid and
heated to 1 800C in small portions over a period
of 5 minutes. The reaction mixture is stirred for a further 30 minutes at 1 800C whereafter it is
cooled to room temperature and diluted with 300
ml. water. The precipitated crystals are filtered,
and washed with water and dried. 8.7 g. (92%) of
Rutaecarpine are obtained which after
recrystallization from ethyl acetate melts at
2580C.This melting point is the same as the
melting point of the product of Example 1 and no
change is observed when the melting point of a
mixture of the products of Examples 1 and 2 is
determined.
Example 3 I 0-Methoxy-6,7-dihydro-5H-I 3H-
indolo[2',3' ;3,4] quinazolin-5-one 1 g. of 6-[(4-methoxy-phenyl) hydrazono]6,7,8,9-tetrahydro- ii H-pyrido[2, 1 - b]quinazolin- 11-one is added to 1 5 g. of polyphosphoric acid at 1 600C in small portions over a period of 5 minutes, with stirring. After 20 minutes the reaction mixture is cooled from 1 600C to room temperature and the pH is adjusted to 6-7 by adding 25 V/W% ammonium hydroxide solution. The precipitated crystals are filtered and washed with water. 0.62 g. (65%) of 1 0-methoxy-6,7-dihydro-5H,1 3H-indolo- [2',3' ;3,4]pyrido[2,1 -b]quinazolin-5-one are obtained which after recrystallization from ethyl acetate melts at 252-2530C.
Analysis for the formula C1sH1sN3 2 Calculated:
C71.91%H4.76%N 13.24%
Found:
C 71.32% H 4.66% N 13.30%
Claims (22)
1. A process for the preparation of compounds of the general formula:
(wherein
i) R1, R2, R3 and R4 each represents a hydrogen atom and R represents a methoxy, benzyloxy, hydroxy or methoxycarbonyl group;
ii) R, R' and R4 each represent a hydrogen atom, R3 represents a methoxy group and R2 represents a hydrogen atom or a hydroxy, benzyloxy or methoxy group;
iii) R, R2, R3 and R4 each represent a hydrogen atom and R1 represents a hydroxy or methoxy group;
iv) R represents a methoxy group, R1 and R4 each represent a hydrogen atom and R2 and R3 each represent a methoxy group;
v) R, R1 and R4 each represent a hydrogen atom and R2 and R3 together form a methylenedioxy group;
vi) R, R', R3 and R4 each represent a hydrogen atom and R2 represents a methoxy group;
vii) R, R1, R2 and R3 each represent a hydrogen atom and R4 represents a methoxy group; or
viii) R, R1, R2, R3 and R4 each represent a hydrogen atom) and the acid addition salts thereof, which process comprises the cyclization of a compound of the formula:
(wherein R, R1, R2, R3 and R4 are as herein defined) or an acid addition salt thereof in the presence of a
Fischer indole catalyst and if desired converting a compound of formula I obtained into an acid addition salt thereof.
2. A process as claimed in claim 1 wherein the cyclization is effected at an elevated temperature up to 2200 C.
3. A process as claimed in claim 1 or claim 2 wherein the Fischer indole catalyst comprises an acid.
4. A process as claimed in claim 3 wherein the acid comprises an organic acid, an inorganic acid and/or a Lewis acid.
5. A process as claimed in claim 4 wherein the inorganic acid comprises phosphoric acid, hydrogen chloride, hydrogen bromide or sulphuric acid.
6. A process as claimed in claim 4 wherein the inorganic acid comprises polyphosphoric acid.
7. A process as claimed in claim 4 wherein the organic acid comprises an alkanoic acid.
8. A process as claimed in claim 7 wherein the alkanoic acid comprises acetic acid, propionic acid or carpronic acid.
9. A process as claimed in claim 4 wherein the
Lewis acid comprises a metal halide.
1 0. A process as claimed in claim 9 wherein the metal halide comprises aluminium chloride or zinc chloride.
ii. A process as claimed in any one of the preceding claims wherein the cyclization is effected at a temperature of from 30 to 2200C.
12. A process as claimed in claim 5 wherein the cyclization is effected at a temperature of from 100 to 2200C.
13. A process as claimed in claim 12 wherein
the cyclization is effected at a temperature of from 140 to 2i00C. A
14. A process as claimed in claim 13 wherein the cyclization is effected at a temperature of from 1600 to 2000C.
1 5. A process as claimed in any one of claims
12 to 14 wherein 5 to 20 parts by weight of polyphosphoric acid are used per 1 part by weight of the compound of formula II or an acid addition salt thereof.
16. A process as claimed in any one of the preceding claims wherein the compound of formula II is used in the form of its hydrogen halide salt.
1 7. A process as claimed in claim 1 6 wherein the compound of formula II is used in the form of its hydrochloride salt.
18. A process as claimed in any one of the preceding claims wherein a compound of formula
I obtained is converted into an acid addition salt by reaction of the compound of formula I with hydrochloric, sulphuric, acetic or fumaric acid.
1 9. A process as claimed in claim 1 substantially as herein described.
20. A process for the preparation of compounds of formula I as defined in claim 1 or an acid addition salt thereof substantially as herein described in any one of the Examples.
21. A compound of formula I or an acid addition salt thereof when prepared by a process as claimed in any one of the preceding claims.
22. Rataecarpine or an acid addition salt thereof when prepared by a process as claimed in any one of claims 1 to 20.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU155880A HU182146B (en) | 1980-06-24 | 1980-06-24 | New process for producing rutecarpine |
| HU801557A HU183171B (en) | 1980-06-24 | 1980-06-24 | New process for producing indolo-bracket-2,3-c-bracket closed-quinazolino-bracket-3,2-a-bracket closed-pyridin-5-ones |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| GB2078224A true GB2078224A (en) | 1982-01-06 |
| GB2078224B GB2078224B (en) | 1984-03-07 |
Family
ID=26317390
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB8119296A Expired GB2078224B (en) | 1980-06-24 | 1981-06-23 | The preparation of indolo(2'3';3'4)-pyrido-(2,1-b)quinazolin-5-ones |
Country Status (4)
| Country | Link |
|---|---|
| AT (1) | AT379397B (en) |
| DE (1) | DE3124578A1 (en) |
| FR (1) | FR2485538B1 (en) |
| GB (1) | GB2078224B (en) |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2447921A1 (en) * | 1979-02-05 | 1980-08-29 | Synthelabo | IMIDAZO AND PYRIMIDO-PYRIDO-INDOLES AND THEIR APPLICATION IN THERAPEUTICS |
-
1981
- 1981-06-22 FR FR8112208A patent/FR2485538B1/en not_active Expired
- 1981-06-23 DE DE19813124578 patent/DE3124578A1/en not_active Withdrawn
- 1981-06-23 GB GB8119296A patent/GB2078224B/en not_active Expired
- 1981-06-23 AT AT277281A patent/AT379397B/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| DE3124578A1 (en) | 1982-09-02 |
| GB2078224B (en) | 1984-03-07 |
| FR2485538A1 (en) | 1981-12-31 |
| FR2485538B1 (en) | 1985-01-11 |
| ATA277281A (en) | 1985-05-15 |
| AT379397B (en) | 1985-12-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US4965369A (en) | Method for preparing indole carboxylic acid derivatives | |
| SK283652B6 (en) | Process for preparing N,N,6-trimethyl-2-(4-methylphenyl)-imidazo- [1,2-a]-pyridine-3-acetamide and salts thereof | |
| EP0213850B1 (en) | Decyanation of pergolide intermediate | |
| USRE31429E (en) | Process for preparation of 9-(dihalobenzyl)adenines | |
| EP0219256B1 (en) | N-alkylation of dihydrolysergic acid | |
| SU930902A1 (en) | Derivatives of thieno(3,2-b)indole | |
| US3775417A (en) | Selective hydrogenation of tri-and tetrazoloisoquinolines | |
| GB2078224A (en) | The Preparation of Indolo[2 min ,3 min ;3,4]-pyrido[2,1b]-quinazolin-5-ones | |
| US5053513A (en) | Method of reducing a carbonyl containing acridine | |
| US4958029A (en) | Process for the production of isoindoline derivatives, novel intermediates and process for their production | |
| US4182880A (en) | 1,8-Naphthyridine compounds and process for preparing the same | |
| US20030120068A1 (en) | Novel synthesis and crystallization of piperazine ring-containing compounds | |
| EP0050492B1 (en) | 1,1-disubstituted-hexahydro-indolo(2,3-a)quinolizine derivatives and their use in the enantioselective synthesis of optically active 14-oxo-e-homo-eburnane derivatives | |
| US4485248A (en) | Process for producing 2,4-diamino-(3,5-dimethoxy-4-methoxyethoxy-benzyl)-pyrimidine | |
| JPS6148839B2 (en) | ||
| US4423219A (en) | Production of purine derivatives and intermediates therefor | |
| NL7809726A (en) | NEW TETRACYCLIC CONNECTIONS. | |
| US4777255A (en) | Process for preparing a purine derivative | |
| US4552967A (en) | Process for the synthesis of intermediates in the preparation of diaminopyridines | |
| FI78291C (en) | FOR EXAMINATION OF THERAPEUTIC FRAME THERAPEUTIC 1-PHENOXY-3-HYDROXY-INDOLYL-ALKYLAMINO-3-PROPANOLER. | |
| US4992568A (en) | Synthesis of benzofurans | |
| Rádl et al. | Synthesis of 1, 2, and 9-methyl derivatives of 4, 9-dihydro-6-methoxy-3-methyl-4-oxo-1H (2H)-pyrazolo [3, 4-b] quinoline and 4, 9-dihydro-6-hydroxy-3-methyl-4-oxo-1H (2H)-pyrazolo [3, 4-b] quinoline and their antiviral activity | |
| HU183171B (en) | New process for producing indolo-bracket-2,3-c-bracket closed-quinazolino-bracket-3,2-a-bracket closed-pyridin-5-ones | |
| US4098787A (en) | Process for preparation of 9-(dihalobenzyl) adenines | |
| SE503224C2 (en) | Benzofuranylimidazole derivatives, process for their preparation and therapeutic compositions containing the same |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 746 | Register noted 'licences of right' (sect. 46/1977) | ||
| PCNP | Patent ceased through non-payment of renewal fee |