IE49400B1 - 2-benzyl-3-(-3-chloro or hydroxy propylithio)-indazole,their corresponding sulfoxides and sulfones and process for their preparation - Google Patents
2-benzyl-3-(-3-chloro or hydroxy propylithio)-indazole,their corresponding sulfoxides and sulfones and process for their preparationInfo
- Publication number
- IE49400B1 IE49400B1 IE239583A IE239583A IE49400B1 IE 49400 B1 IE49400 B1 IE 49400B1 IE 239583 A IE239583 A IE 239583A IE 239583 A IE239583 A IE 239583A IE 49400 B1 IE49400 B1 IE 49400B1
- Authority
- IE
- Ireland
- Prior art keywords
- benzyl
- indazole
- preparation
- sulfones
- chloro
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 title claims description 5
- 150000003462 sulfoxides Chemical class 0.000 title claims description 5
- 150000003457 sulfones Chemical class 0.000 title claims description 4
- 238000000034 method Methods 0.000 title claims 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 9
- WHWSDZHLYUEYMX-UHFFFAOYSA-N 2-benzyl-3-(3-chloropropylsulfanyl)indazole Chemical compound N1=C2C=CC=CC2=C(SCCCCl)N1CC1=CC=CC=C1 WHWSDZHLYUEYMX-UHFFFAOYSA-N 0.000 claims description 3
- LAMUXTNQCICZQX-UHFFFAOYSA-N 3-chloropropan-1-ol Chemical compound OCCCCl LAMUXTNQCICZQX-UHFFFAOYSA-N 0.000 claims description 3
- 159000000000 sodium salts Chemical class 0.000 claims description 3
- 241001061127 Thione Species 0.000 claims description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- VTVTYUPZEYQFFH-UHFFFAOYSA-N 3-(2-benzylindazol-3-yl)sulfanylpropan-1-ol Chemical compound N1=C2C=CC=CC2=C(SCCCO)N1CC1=CC=CC=C1 VTVTYUPZEYQFFH-UHFFFAOYSA-N 0.000 description 2
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 239000012454 non-polar solvent Substances 0.000 description 2
- 150000004965 peroxy acids Chemical class 0.000 description 2
- 239000002798 polar solvent Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- MFESCIUQSIBMSM-UHFFFAOYSA-N I-BCP Chemical compound ClCCCBr MFESCIUQSIBMSM-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 230000003444 anaesthetic effect Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000000645 desinfectant Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000009434 installation Methods 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
The present invention relates to intermediates useful in the preparation of 2-benzyl-3-(3-dimethylaminopropylthio2H-indazole (I) as well as its sulfoxide (II) and its su1fone (III):
x
N
II
The above compounds are described and claimed in our Rccfent
- 3 Pharmacological studies carried out on laboratory animals have shown that the above compounds possess an antiinflamatory activity, which manifests itself both through the topical and the systemic route, as well as a local anaesthetic activity and a disinfectant action which manifest themselves only after topical application.
In the above compounds (I), (II) and (III) may be prepared by a variety of routes including the reaction of 2-benzylindazolin-3-thione (IV) with l-bromo-3-chloro (or hydroxy) propane according to the following scheme.
Where X is Cl or OH.
- 4 The novel intermediate compounds of the present invention are those of formula (VI) and the corresponding sulfoxides and sulfones.
In the above reaction scheme the 2-benzyl-indazolin-35 thione (IV) reacts easily with 1-bromo-3-chloropropane in the presence of a base both in polar and non-polar solvents, to give the 2-benzyl-3-(3-chloropropylthio)indazole (VI ) in good yields, a
For X = OH, the 2-benzyl-3-(3-hydroxypropylthio)10 indazole may also be prepared by the action of the 3ch1oropropanol on the sodium salt of (IV).
Compound (VI) (X = chlorine) reacts with solutions of dimethylamine in both polar and non-polar solvents to give (I) as the hydrochloride.
The use of gaseous dimethylamine is obviously possible but in general, unless special installations are used, it is less advantageous as will become clear to one skilled in the art.
When then, in (VI), X = OH, the reaction with dimethylamine will require the use of a catalyst, such as dicyclohexylcarbodi i mi de.
- 5 Also in accordance with the present invention compound (VI) may be oxidized with peracids to provide the corresponding sulfoxides and sulfones (VII and VIII) according to the peracid used and the reaction conditions selected.
By action ofihe dimethylamine in conditions similar to that described for the preparation of (I), from (VII) and (VIII) there can then be obtained (II) and (III):
The present invention is illustrated by the following Examples.
- 6 EXAMPLE 1
2-benzyl-3-(3-chloropropylthio)-indazole
2-benzyl-indazolin-3-thione (44.3 g, 0.185 mols) is dissolved in a solution of 12.9 g (0.230 mols) of KOH in 500 ml of water. When the solution is completed there is added 31.9g (0.203 mols) of l-bromo-3-chloropropane. The mixture is heated with stirring on a steam bath for 3 hours and is then cooled.
The oil which forms is extracted with ether and the 10 residue which is obtained by removing the solvent (59 g;
yield: 100%) results unitary under TLC and its NMR is in accordance with the expected structure.
EXAMPLE 2
2-benzyl-3-(3-hydroxypropylthio)-indazole
To a solution of 0.92 g (0.04 mols) of sodium in 100 ml of absolute ethanol there is added 9.6 g (0.04 mols) of 2benzyl-indazolin-3-thione. The ethanol is removed on a steam bath under reduced pressure and the dry sodium salt thus obtained is suspended in 50 ml of 3-chloropropanol.
The mixture is heated for 3 hours with stirring in a bath kept at a temperature of 180°. At the end of the heating cycle the mixture is poured in water and extracted with
- 7 ether. The ether extract is dried and the solvent is removed under high vacuum while it is heated in an oil bath at 130° to eliminate also the excess portion of 3-chloropropanol which has been extracted with the ether.
The oily residue is purified by chromatography on a silica gel column, using as the eluent ethyl acetate.
The resulting oil (7.3 g - yield: 61%), which tends to decompose if distillation thereof is attempted, shows by elemental analysis and under NMR spectrum to consist of practically pure 2-benzyl-3-(3-hydroxypropylthio)-indazole.
Claims (7)
1. 2-Benzyl-3-(3-chloropropylthio)-indazole.
2. A method for the preparation of the compound claimed in claim 1, which comprises reacting 2-benzyl-indazolin-35 thione in the presence of a base with l-bromo-3-chloropropane.
3. 2-Benzy1-3-(3-hydroxypropylthio)-indazole.
4. A method for the preparation of the compound claimed in claim 3, which comprises reacting the sodium salt of 2benzyl-indazolin-3-thione with 3-chloropropanol. io
5. The sulfoxides and sulfones of the compounds claimed in claim 1 and 3. ejj tlai-m 1,3 et S'
6. A compoundsubstantially as hereinbefore described with reference to the Examples. (x&Jxl/K'ng a. J 4/3 trt-5
7. A methodjjubstantially as hereinbefore described with 15 reference to the Examples.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT20305/79A IT1110282B (en) | 1979-02-19 | 1979-02-19 | BASIC THIO-INDAZOLS |
| IE296/80A IE49399B1 (en) | 1979-02-19 | 1980-02-18 | Basic thio-indazoles |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IE832395L IE832395L (en) | 1980-08-19 |
| IE49400B1 true IE49400B1 (en) | 1985-10-02 |
Family
ID=26318851
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IE239583A IE49400B1 (en) | 1979-02-19 | 1980-02-18 | 2-benzyl-3-(-3-chloro or hydroxy propylithio)-indazole,their corresponding sulfoxides and sulfones and process for their preparation |
| IE239680A IE49401B1 (en) | 1979-02-19 | 1980-02-18 | N,n-dimethyl-(3-(2-benzyl-2h-indazole-3-yl)propionic acid amide |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IE239680A IE49401B1 (en) | 1979-02-19 | 1980-02-18 | N,n-dimethyl-(3-(2-benzyl-2h-indazole-3-yl)propionic acid amide |
Country Status (1)
| Country | Link |
|---|---|
| IE (2) | IE49400B1 (en) |
-
1980
- 1980-02-18 IE IE239583A patent/IE49400B1/en unknown
- 1980-02-18 IE IE239680A patent/IE49401B1/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| IE49401B1 (en) | 1985-10-02 |
| IE832395L (en) | 1980-08-19 |
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