NZ211831A - The preparation of 3-cyano-4-aminoacetophenones and their use as intermediates in preparing 2-amino-5-(1-hydroxy-2-(alkyl- or dialkyl-amino)ethyl) benzonitriles - Google Patents
The preparation of 3-cyano-4-aminoacetophenones and their use as intermediates in preparing 2-amino-5-(1-hydroxy-2-(alkyl- or dialkyl-amino)ethyl) benzonitrilesInfo
- Publication number
- NZ211831A NZ211831A NZ211831A NZ21183185A NZ211831A NZ 211831 A NZ211831 A NZ 211831A NZ 211831 A NZ211831 A NZ 211831A NZ 21183185 A NZ21183185 A NZ 21183185A NZ 211831 A NZ211831 A NZ 211831A
- Authority
- NZ
- New Zealand
- Prior art keywords
- general formula
- compounds
- preparation
- cyano
- temperature
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 title claims description 12
- 239000000543 intermediate Substances 0.000 title claims 2
- 150000008359 benzonitriles Chemical class 0.000 title 1
- 125000004663 dialkyl amino group Chemical group 0.000 title 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 28
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 27
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims abstract description 21
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims abstract description 15
- 239000011541 reaction mixture Substances 0.000 claims abstract description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 7
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims abstract description 6
- 229910052731 fluorine Chemical group 0.000 claims abstract description 4
- 125000001153 fluoro group Chemical group F* 0.000 claims abstract description 4
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims abstract description 3
- 239000001257 hydrogen Substances 0.000 claims abstract description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 3
- 229910052700 potassium Inorganic materials 0.000 claims abstract description 3
- 239000011591 potassium Substances 0.000 claims abstract description 3
- 238000000034 method Methods 0.000 claims description 19
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 8
- -1 alkali metal methoxide Chemical class 0.000 claims description 7
- 238000010992 reflux Methods 0.000 claims description 5
- 238000007127 saponification reaction Methods 0.000 claims description 5
- 229910052783 alkali metal Inorganic materials 0.000 claims description 4
- 150000008044 alkali metal hydroxides Chemical class 0.000 claims description 4
- 238000002844 melting Methods 0.000 claims description 4
- 230000008018 melting Effects 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
- 229910021589 Copper(I) bromide Inorganic materials 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 claims description 2
- 238000000967 suction filtration Methods 0.000 claims description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims 2
- 239000000725 suspension Substances 0.000 claims 2
- 241001125671 Eretmochelys imbricata Species 0.000 claims 1
- 150000001340 alkali metals Chemical class 0.000 claims 1
- 238000001816 cooling Methods 0.000 claims 1
- 150000001879 copper Chemical class 0.000 claims 1
- 239000012043 crude product Substances 0.000 claims 1
- 239000000284 extract Substances 0.000 claims 1
- 239000003208 petroleum Substances 0.000 claims 1
- CASUWPDYGGAUQV-UHFFFAOYSA-M potassium;methanol;hydroxide Chemical compound [OH-].[K+].OC CASUWPDYGGAUQV-UHFFFAOYSA-M 0.000 claims 1
- 238000001556 precipitation Methods 0.000 claims 1
- 239000002904 solvent Substances 0.000 abstract description 4
- 238000004519 manufacturing process Methods 0.000 abstract description 3
- 238000009835 boiling Methods 0.000 abstract 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 3
- 239000013543 active substance Substances 0.000 description 3
- 239000003674 animal food additive Substances 0.000 description 3
- 125000004093 cyano group Chemical group *C#N 0.000 description 3
- 230000020176 deacylation Effects 0.000 description 3
- 238000005947 deacylation reaction Methods 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 230000031709 bromination Effects 0.000 description 2
- 238000005893 bromination reaction Methods 0.000 description 2
- 238000001311 chemical methods and process Methods 0.000 description 2
- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 2
- QTMDXZNDVAMKGV-UHFFFAOYSA-L copper(ii) bromide Chemical compound [Cu+2].[Br-].[Br-] QTMDXZNDVAMKGV-UHFFFAOYSA-L 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 239000013067 intermediate product Substances 0.000 description 2
- 235000020997 lean meat Nutrition 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 229910021590 Copper(II) bromide Inorganic materials 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 125000004442 acylamino group Chemical group 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 229940125773 compound 10 Drugs 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- NBTOZLQBSIZIKS-UHFFFAOYSA-N methoxide Chemical compound [O-]C NBTOZLQBSIZIKS-UHFFFAOYSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- WECHHDJTILFYQT-UHFFFAOYSA-N n-(4-acetylphenyl)acetamide Chemical compound CC(=O)NC1=CC=C(C(C)=O)C=C1 WECHHDJTILFYQT-UHFFFAOYSA-N 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 150000002927 oxygen compounds Chemical class 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 1
- 244000144977 poultry Species 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
1. Process for preparing 3-cyano-4-amino-acetophenones of general formula see diagramm : EP0158932,P4,F1 wherein R represents a hydrogen or fluorine atom, characterized in that a 3-cyano-4-acetamino-acetophenone of general formula see diagramm : EP0158932,P4,F2 wherein R is defined as hereinbefore, is saponified with potassium hydroxide, sodium hydroxide, potassium or sodium methoxide in the presence of methanol as solvent at temperatures up to the boiling point of the reaction mixture and the compound of general formula I is isolated from the reaction mixture.
Description
New Zealand Paient Spedficaiion for Paient Number £11 831
\t I
\ 17 APR 1985 '
i *
Patents form No.5
NEW ZEALAND PATENTS ACT 1953 COMPLETE SPECIFICATION
"CHEMICAL PROCESS"
-I-»WE DR. KARL THOMAE GESELLSCHAFT MIT BESCHRANKTER HAFTUNG
a Body Corporate organised under the laws of the Federal Republic of Germany, of D-7950 Biberach an der Riss, Federal Republic of Germany hereby declare the invention, for which -I-/we pray that a patent may be granted to me/us, and the method by which it is to be performed, to be particularly described in and by the following statement:-
2 1*831
2
IIP 147-122
Chemical Process
The invention relates to a process for the preparation of 3-cyano-4-arainoacetophenones of general formula I
R
0 \l
(I)
h2n c - ch3.
CN
(wherein R represents a hydrogen or fluorine atom).
These compounds are important intermediate products in the preparation of valuable pharmaceutical compositions and feed additives; as feed additives/ the compounds of general formula V described hereinafter bring about more intensive use of animal feed,
and may be utilised in animal husbandry for the promotion of more rapid growth and of an increase in the ratio of lean meat to fat.
In view of the worldwide shortage of high-grade protein there is considerable interest in such active substances. In order to provide sufficient quantities of these active substances the discovery of a simple method of production which is environmentally favourable is urgently needed.
The 3-cyano-4-aminoacetophenones of general formula I occupy an important key position in the production of the active substances. It was therefore important to find a simple method of preparing them which ensures not only a high yield but also a high quality product.
Thus, according to the invention there is
211831
provided a process for the preparation of compounds of general formula I as hereinbefore defined, which comprises saponifying a compound of general formula II
(ii)
; 5 (wherein R is as hereinbefore defined) by means of an alkali metal hydroxide (such as, for example,
' potassium hydroxide or sodium hydroxide) or an
■ri alkali metal methoxide (such as, for example, potassium
.J ' methoxide or sodium methoxide) , and in the presence
of methanol.
j In a preferred embodiment, potassium hydroxide
\>
/ is placed in methanol and the mixture is heated i
; to a temperature of between 30 and 50°C, and then,
j
, preferably gradually, the compound of general formula
^ 15 II is added thereto. The saponification is completed j by heating the reaction mixture to a temperature j of between 40°C and the reflux temperature, preferably
\ to the reflux temperature, and maintaining the reaction mixture at this temperature until the 20 saponification reaction is completed. If the reaction mixture is then evaporated to dryness, the residue taken up in water and the solution mixed with an inorganic acid (preferably concentrated hydrochloric y ^
» acid) the compound of general formula I is obtair^d
! 'V
J 25 as a crystalline precipitate. The precipitate ;• -
"t ii 17 FEB1988
j is washed once more and dried. The corresponding /
' A
compound of general formula I occurs in pure form.'v<v /•
... £ !M *
Generally, for the compound wherein R represents
' a hydrogen atom, yields of between 80 and 90% of theory
may be achieved, based on the compound of general formula
II used; if R represents a fluorine atom the yields are
2 1183 1
somewhat lower.
The saponification of the compounds of general formula II to form compounds of general formula I under the conditions specified above was not foreseeable. The deacylation of compounds of general formula II cannot be carried out either in acidic or in alkaline aqueous media in the desired manner when using conventional methods of saponification. As is also known from the literature [cf. A. Graham, Synthetic Communications 10 [3], 241-243 (1980)J, a compound possessing a reactive cyano group adjacent to an acylamino group undergoes, in the presence of a strong acid, a cyclisation reaction according to the reaction plan which follows:
or with dilute acids the corresponding 2-acylaminobenzamide is obtained. It has also been observed that in aqueous alkaline medium the cyano group is also saponified to form the amide group. This method i3 used for the preparative recovery of condensed pyrimidines.
By using the process according to the invention it has been possible for the first time to carry out the deacylation of the acetyl group whilst maintaining the integrity of the cyano group; this deacylation is possible only if alkali metal hydroxides in methanol or alkali metal methoxides in methanol are used.
The starting compounds of general formula II may be obtained, for example, by reacting a
compound of general formula IV
211831
o ii ch3 - c -
(IV)
(wherein R is as hereinbefore defined) with copper(I) cyanide.
The reaction is conveniently carried out in the presence of a solvent such as, for example, pyridine or dimethylformamide at temperatures of between 100 and 150°C, and the product is purified with, for example, ethyl acetate (cf. also Houben-Weyl, Volume 8: Oxygen Carpounds III, page 303 (available on request)).
The starting compounds of general formula IV may be obtained, for example, from the corresponding 4-acetamidoacetophenone (for the preparation thereof see Beilstein E II, 14, 33) by bromination using bromine in the presence of glacial acetic acid/water [cf. L.C. Raiford, H.L. Davis, J. Am. Chem. Soc. 50, 158 (1928) and Beilstein E II, 3_4, 33 (available on request)].
The compounds of general formula I are important intermediate products for the preparation of compounds of general formula V
R
H2n ch - ch2 - n oh x"l
(V)
cn
(wherein R is as hereinbefore defined, R^ represents a hydrogen atom or a C1-4 alkyl group and Rj represents
211831
a C}_4 alkyl group) which may be used, for example, as feed additives, and which bring about greater growth in fat-stock and poultry and also lead to increased utilisation of feed; they also increase 5 the ratio of lean meat to fat (cf. New Zealand Patents 194308 and 196249). However, these compounds also have therapeutically useful properties, for example an effect on the B-receptors, particularly a Sj"
mimetic activity. A particularly interesting compound 10 of general formula V is that compound wherein R
and R^ each represents a hydrogen atom and R2 represents an isopropyl group (melting point 165-167°C).
The compounds of general formula V may readily be prepared from the corresponding 3-cyano-4-aminoaceto-15 phenone by the following steps:
a) bromination, in conventional solvents such as,
for example, glacial acetic acid or tetrahydrofuran, using elemental bromine or copper (II) bromide;
b) reaction, at temperatures of up to 20°C, of
the resulting05-bromo-3-cyano-4-aminoacetophenone with an amine of general formula HNR^R2 (wherein R^ and R2 are as hereinbefore defined) to form the corresponding aminoketone; and c) reduction of the aminoketone, to form the amino-25 alcohol of general formula V, with the aid of sodium borohydride in water.
i o
3 1
The following non-limiting Examples are intended to illustrate the invention more fully:
A. Examples of the preparation of the end products
Example 1
3-Cyano-4-aminoacetophenone
.2 g (0.45 mol) of potassium hydroxide and 300 ml of methanol are placed in a reaction vessel and the contents of the vessel are heated \ 10 to 40°C. Within 2 to 4 minutes 30 g (0.15 mol)
of 3-cyano-4-acetamidoacetophenone is added and the reaction mixture is heated under reflux for 20 minutes. It is then concentrated by evaporation to dryness and the residue is mixed with 300 ml 15 of water; 40 ml of concentrated hydrochloric acid is added and the crystalline 3-cyano-4-aminoacetophenone formed is precipitated. The mixture is cooled i to 10°C and stirred for a further hour. After
* suction filtration, washing of the filter residue
with water and drying of the residue at 60°C, 21 g of beige 3-cyano-4-aminoacetophenone is obtained, corresponding to a yield of 87.5% of theory. Melting point: 161.5°C.
If sodium hydroxide and methanol are used 25 in the same molar ratios and under the same reaction conditions, 3-cyano-4-aminoacetophenone is obtained in a yield of 80% of theory.
Example 2 30 3-Cyano-4-ami noacetophenone ^ 3.8 kg (59.6 mol) of potassium hydroxide
^ and 45.6 litres of methanol are placed in a reaction vessel and the contents of the vessel are heated to 40°C. Within 5 to 10 minutes 4.58 kg (22.6 mol) 35 of 3-cyano-4-acetamidoacetophenone is added; the mixture is refluxed for 25 minutes, the solvent
~c*
J
"3
2 118
is eliminated and 60 litres of water, followed by 6 litres of concentrated hydrochloric acid,
are added to the dry residue. The work-up is continued as described in Example 1.
Yield: 3.0 kg of 3-cyano-4-aminoacetophenone corresponding to 82.8% of theory.
Melting point: 161.5°C.
Using potassium methoxide, a yield of 76% of theory is obtained.
Example 3
3-Cyano-4-amino-5-fluoroacetophenone
Using the same method as in Example 1, 3-cyano-4-acetaraido-5-fluoroacetophenone is saponified 15 with potassium hydroxide, at 45 to 50°C with a reaction time of 24 hours, to form 3-cyano-4-amino-5-fluoroacetophenone.
Yield: 55% of theory; using sodium hydroxide 48% of theory.
B. Example of the preparation of the starting compound 3-cyano-4-acetamidoacetophenone
Example 4
In accordance with Rosenmund-V.Braun's reaction 25 (as described in Houben-Weyl, Volume 8: Oxygen Compounds III, page 303), 70 g (0.273 mol) of 3-bromo-4-acetamidoacetophenone [prepared using the method of L.C. Raiford and H.L. Davis, J. Am.
Chem. Soc. 50, 158 (1928)) and 24.5 g (0.273 mol) 30 of copper(I) cyanide are heated in 150 ml of dimethyl-formamide in an oil bath to 130°C for 2.5 hours.
Copper(I) bromide is precipitated, which is suction filtered at the end of the reaction, using a suction filter at 95°C, and washed with 20 ml of dimethylformamide. 35 The warm filtrate is poured into 300 ml of water,
whereupon the 3-cyano-4-acetamidoacetophenone and
Claims (10)
1. A process for the preparation of compounds of general formula I r J 0 h2h - 12w - ch3. (i) cn (wherein R represents a hydrogen or fluorine atom) which comprises saponifying a compound of general formula II (ii) 10 (wherein R is as defined above) by means of an alkali metal hydroxide or an alkali metal methoxide^ in the presence of methanol.
2. A process as claimed in claim 1 wherein the alkali metal hydroxide comprises potassium hydroxide 15 or sodium hydroxide. A* 6 /
3. A process as claimed in claim 1 wherein the |z ^ p£B1983' ' alkali metal methoxide comprises potassium methoxide^ or sodium methoxide.
4. A process as claimed in claim 1 wherein the 20 compound of general formula II is gradually added over a period of a few minuteo; to a potassium hydroxide-methanol mixture which has been pre-warmed to a temperature of between 30 and 50°C. ' E I yj .'<*» -11- 21183.1
5. A process as claimed in any one of the preceding claims wherein the reaction mixture is heated to a temperature of between 40°C and the reflux temperature and maintained at such a temperature until the 5 saponification reaction is completed.
6. A process as claimed in claim 5 wherein the said temperature is the reflux temperature of the reaction mixture.
^ 7. A process for the preparation of compounds ^ 10 of general formula I as described in claim 1 substantially as herein described.
8. A process for the preparation of compounds of general formula I as described in claim 1 substantially as herein described in any one of Examples 15 1 to 3.
9. Compounds of general formula I as described in claim 1 whenever prepared by a process as claimed in any one of the preceding claims.
10. Use of the compounds of general formula I 20 as described in claim 1 when prepared by a process as claimed in any one of claims 1 to 8 as intermediates in the preparation of compounds of formula V % t' J k OH CN CH - CH2 - (V) E f/ S O s 'fry *17 FEB/983,f 25 - . r- ^ e iv" ■ (wherein R is as defined in claim 1, represents a hydrogen atom or a C^_^ alkyl group and Rj represents a C1-4 alkyl group). DR KARL THOMAE GmbH By their Attorneys BALDWIN SON & CAREY C. QoucJLa^&f-y
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE3414628A DE3414628C1 (en) | 1984-04-18 | 1984-04-18 | Process for the preparation of 3-cyano-4-aminoacetophenones |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NZ211831A true NZ211831A (en) | 1988-03-30 |
Family
ID=6233895
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NZ211831A NZ211831A (en) | 1984-04-18 | 1985-04-17 | The preparation of 3-cyano-4-aminoacetophenones and their use as intermediates in preparing 2-amino-5-(1-hydroxy-2-(alkyl- or dialkyl-amino)ethyl) benzonitriles |
Country Status (11)
| Country | Link |
|---|---|
| EP (1) | EP0158932B1 (en) |
| JP (1) | JPH0625098B2 (en) |
| AT (1) | ATE26259T1 (en) |
| AU (1) | AU571079B2 (en) |
| DE (2) | DE3414628C1 (en) |
| ES (1) | ES542338A0 (en) |
| HK (1) | HK97090A (en) |
| HU (1) | HU193109B (en) |
| IL (1) | IL74919A (en) |
| NZ (1) | NZ211831A (en) |
| SG (1) | SG25490G (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2700469C (en) | 2007-10-11 | 2016-11-15 | Cube Investments Limited | Capacitive probes and sensors, and applications therefor, and multimode wireless devices |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2354961C2 (en) * | 1973-11-02 | 1983-02-10 | Dr. Karl Thomae Gmbh, 7950 Biberach | Process for the preparation of aminophenylethanolamines |
| DE2337951C2 (en) * | 1973-07-26 | 1984-07-26 | Hoechst Ag, 6230 Frankfurt | Process for the preparation of 4-amino-2,5-dialkoxybenzonitriles |
| CH584716A5 (en) * | 1973-12-15 | 1977-02-15 | Ciba Geigy Ag | |
| US4407819A (en) * | 1980-08-25 | 1983-10-04 | American Cyanamid Company | Phenylethanolamine derivatives and acid addition salts thereof for the depression of fat deposition in warm blooded animals |
-
1984
- 1984-04-18 DE DE3414628A patent/DE3414628C1/en not_active Expired
-
1985
- 1985-04-03 AT AT85104068T patent/ATE26259T1/en not_active IP Right Cessation
- 1985-04-03 DE DE8585104068T patent/DE3560108D1/en not_active Expired
- 1985-04-03 EP EP85104068A patent/EP0158932B1/en not_active Expired
- 1985-04-16 IL IL74919A patent/IL74919A/en not_active IP Right Cessation
- 1985-04-17 JP JP60080451A patent/JPH0625098B2/en not_active Expired - Lifetime
- 1985-04-17 AU AU41356/85A patent/AU571079B2/en not_active Ceased
- 1985-04-17 ES ES542338A patent/ES542338A0/en active Granted
- 1985-04-17 NZ NZ211831A patent/NZ211831A/en unknown
- 1985-04-17 HU HU851435A patent/HU193109B/en not_active IP Right Cessation
-
1990
- 1990-03-30 SG SG254/90A patent/SG25490G/en unknown
- 1990-11-22 HK HK970/90A patent/HK97090A/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| DE3560108D1 (en) | 1987-05-07 |
| HUT37592A (en) | 1986-01-23 |
| JPH0625098B2 (en) | 1994-04-06 |
| ATE26259T1 (en) | 1987-04-15 |
| HK97090A (en) | 1990-11-30 |
| EP0158932A1 (en) | 1985-10-23 |
| ES8603386A1 (en) | 1985-12-16 |
| HU193109B (en) | 1987-08-28 |
| ES542338A0 (en) | 1985-12-16 |
| AU571079B2 (en) | 1988-03-31 |
| SG25490G (en) | 1990-09-07 |
| JPS60233046A (en) | 1985-11-19 |
| IL74919A (en) | 1988-10-31 |
| AU4135685A (en) | 1985-10-24 |
| IL74919A0 (en) | 1985-08-30 |
| EP0158932B1 (en) | 1987-04-01 |
| DE3414628C1 (en) | 1985-06-27 |
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