GB1563388A - Isoxazole-4-carboxamide derivatives - Google Patents
Isoxazole-4-carboxamide derivatives Download PDFInfo
- Publication number
- GB1563388A GB1563388A GB214679A GB214679A GB1563388A GB 1563388 A GB1563388 A GB 1563388A GB 214679 A GB214679 A GB 214679A GB 214679 A GB214679 A GB 214679A GB 1563388 A GB1563388 A GB 1563388A
- Authority
- GB
- United Kingdom
- Prior art keywords
- compound
- formula
- isoxazole
- ethyl
- stated
- 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.)
- Expired
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
- C07D261/10—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D261/18—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Description
(54) ISOXAZOLE-4-CARBOXAMIDE DERIVATIVES
(71) We, SANDOZ LTD., of 35
Lichtstrasse, 4002 Basle, Switzerland, a
Swiss Bcdy Corporate, do hereby declare the invention, for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement:- The invention provides compounds of formula I,
in which
R1 is Ct 4alkyl, or C36cycloalkyl, R2 is hydrogen, fluorine, chlorine or C, 4alkyl or alkoxy,
R3 is straight chain Ct~4alkyl, and
Y is
or
The invention also provides processes for the production of compounds of formula I, characterised by
a) producing a compound of formula Ia,
in which Rt, R2 and R3 are as defined above, by oxidisine a compound of formula Ib,
in which R1, R2 and R3 are as defined above, or
b) producing a compound of formula Ib, stated above, by reacting a compound of formula 11,
in which R1 and R3 are as defined above, with a compound of formula III,
in which
R2 is as defined above, in an inert organic solvent.
The oxidation in process a) is suitably effected with potassium permanganate or, preferably, chromium trioxide, under acid conditions, provided for example by sulphuric, hydrochloric or, preferably, acetic acid, and in the presence of water.
The reaction temperature is suitably from 10 to 50"C, preferably 200 to 300C and the reaction time may vary, for example from I to 5, more usually 1.5 to 2.5 hours.
Suitable solvents for use in process b) include ethers, such as diethyl ether or tetrahydrofuran, and aliphatic hydrocarbons, such as hexane, pentane or heptane, preferably tetrahydrofuran. The reaction temperature may, for example, be from -75" to -550C, preferably -650 to -60"C. and the reaction time may vary, for example from 1 to 5, more usually 2.5 to 3.5 hours.
The resulting compounds of formula I may be isolated and purified using conventional techniques. Where required, non-salt forms thereof may be converted into acid or base addition salt forms thereof in conventional manner, and vice versa..
The compounds of formula II may be produced by reacting a compound of formula IV.
in which R1 and R3 are as defined above, with a compound of formula V,
R4Li V in which
R4 is C1~4alkyl.
The process is suitably effected in the same solvent and under the same conditions as process b), described above.
The compounds of formulae IV and V are either known or may be produced in conventional manner from available materials.
The compounds of formula I are useful as intermediates for the production of pharmaceutically active compounds as described for example in our co-pending application No. 32459/76, Specification
No. . The following Examples illustrate the invention.
EXAMPLE 1: 3 - Ethyl - 5 - (,B - hydroxyphenethyl)
N - methyl - isoxazole - 4 - carboxamide
(compound of formula Ib)
A suspension of 58.5 g (0.348 mole) of 3 ethyl - N,5 - dimethyl - isoxazole - 4 carboxamide in 1 litre of tetrahydrofuran is cooled to -650C and 478 ml of 1.6M nbutyllithium in hexane (0.765 mole) is added, dropwise while maintaining the temperature between -60" and -70"C.
After addition is complete the suspension is stirred for 1+ hours at -600C to -700C, and then 37.2 g (0.350 mole) of benzaldehyde in 375 ml tetrahydrofuran is added, dropwise, while maintaining the temperature between -60" and -70"C.
After addition is complete, the mixture is stirred for 1+ hours at 600 to -700C and then warmed to -300C and quenched by the addition of saturated ammonium chloride solution. The mixture is further diluted with tetrahydrofuran and the layers are separated. The tetrahydrofuran layer is washed twice with 50van brine, and once with brine, dried over anhydrous magnesium sulphate, filtered and evaporated in vacuo.
The solid residue is triturated with ether and filtered to give the heading compound, m.p.
135 to 1370C.
EXAMPLE 2: 3 - Ethyl - N - methyl - 5 - phenacyl - 4
isoxazole carboxamide (compound of
formula Ia)
A solution of 2-9.0 g (0.105 mole) of 3 ethyl -- 5 - (p - hydroxyphenethyl) - N methyl - isoxazole - 4 ~ 4;c'arboxamide and 500 ml of acetic acid, at room temperature, is treated, dropwise, rapidly- with 12.5 g (0.125 mole) of chromium trioxide in 125 ml of water. The resulting solution is stirred for 2 hours at room temperature and a portion of the acetic acid is removed in vacuo. The remainder is poured onto ice/water and extracted with methylene chloride. The methylene chloride layer is washed with 2N sodium hydroxide, dried over anhydrous magnesium sulphate, filtered and evaporated in vacuo. The solid residue is triturated with ether and recrystallised from ethanol to give the heading compound, m.p.
134" to 136"C.
WHAT WE CLAIM IS:
1. A process for the production of a compound of formula I,
in which
R, is C,~4alkyl, or C38cycloalkyl, R2 is hydrogen, fluorine, chlorine or C1~4alkyl or alkoxy,
R3 is straight chain C,~4alkyl, and
Y is
or
comprising
a) producing a compound of formula Ia,
in which R1, R2 and R3 are as defined above, by oxidising a compound of formula Ib,
in which R1, R2 and R3 are as defined above, or
b) producing a compound of formula Ib, stated above, by reacting a compound of formula II,
**WARNING** end of DESC field may overlap start of CLMS **.
Claims (10)
1. A process for the production of a compound of formula I,
in which
R, is C,~4alkyl, or C38cycloalkyl, R2 is hydrogen, fluorine, chlorine or C1~4alkyl or alkoxy,
R3 is straight chain C,~4alkyl, and
Y is
or
comprising
a) producing a compound of formula Ia,
in which R1, R2 and R3 are as defined above, by oxidising a compound of formula Ib,
in which R1, R2 and R3 are as defined above, or
b) producing a compound of formula Ib, stated above, by reacting a compound of formula II,
in which
R, and R3 are as defined above, with a compound of formula III,
in which
R2 is as defined above, in an inert organic solvent.
2. A process for the production of a compound of formula 1, stated in Claim 1, substantially as herein described with reference to Example I or 2.
3. A compound of formula I, stated in
Claim 1, whenever produced by a process according to Claim 1 or 2.
4. A compound of formula I, stated in
Claim 1.
5. A compound of formula Ia, stated in
Claim
6. A compound of formula Ib, stated in
Claim 1.
7. 3 - Ethyl - 5 - ( - hydroxyphenethyl)
N - methyl - isoxazole - 4 - carboxamide.
8. 3 - Ethyl - N - methyl - 5 - phenacyl - 4 isoxazole carboxamide.
9. A compound according to any one of
Claims 3 to 8 in non-salt form.
10. A compound according to any one of
Claims 3 to 8 in acid or base addition salt form.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US60237475A | 1975-08-06 | 1975-08-06 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| GB1563388A true GB1563388A (en) | 1980-03-26 |
Family
ID=24411097
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB214679A Expired GB1563388A (en) | 1975-08-06 | 1976-08-04 | Isoxazole-4-carboxamide derivatives |
Country Status (1)
| Country | Link |
|---|---|
| GB (1) | GB1563388A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3247454A1 (en) * | 1982-12-22 | 1984-06-28 | Laboratorios Bago S.A., Buenos Aires | Substituted 3-phenyl-5-methylisoxazole-4-carboxanilides, process for their preparation and pharmaceutical compositions containing these compounds |
-
1976
- 1976-08-04 GB GB214679A patent/GB1563388A/en not_active Expired
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3247454A1 (en) * | 1982-12-22 | 1984-06-28 | Laboratorios Bago S.A., Buenos Aires | Substituted 3-phenyl-5-methylisoxazole-4-carboxanilides, process for their preparation and pharmaceutical compositions containing these compounds |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PS | Patent sealed | ||
| PCNP | Patent ceased through non-payment of renewal fee |