WO2011121597A1 - A PROCESS FOR THE PREPARATION OF 5-SUBSTITUTED 3-(5-NITRO-4-THIOCYANATOPYRIMIDIN-2-YL)-3H-BENZO [d]-IMIDAZOLE - Google Patents
A PROCESS FOR THE PREPARATION OF 5-SUBSTITUTED 3-(5-NITRO-4-THIOCYANATOPYRIMIDIN-2-YL)-3H-BENZO [d]-IMIDAZOLE Download PDFInfo
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- WO2011121597A1 WO2011121597A1 PCT/IN2010/000221 IN2010000221W WO2011121597A1 WO 2011121597 A1 WO2011121597 A1 WO 2011121597A1 IN 2010000221 W IN2010000221 W IN 2010000221W WO 2011121597 A1 WO2011121597 A1 WO 2011121597A1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
Definitions
- the present invention relates to a novel, facile, industrially viable and cost effective process for manufacturing 5-substituted 3-(5-Nitro-4-thiocyanatopyrimidin-2-yl)-3H- benzo[i ]-imidazole, which is an intermediate for the synthesis of immunosuppressive agents, 8-substituted-2-benzimidazolyl purine.
- R is CN, CI, CF 3 or OCF 3
- a drawback of the process reported in the above patent or in other including WO2008043019, is that the above class of compounds are synthesized from the corresponding 4-substituted 2-nitrobenzenamine by a six stage process, which involves protection, deprotection and reduction sequences that are likely to yield unwanted side products. Moreover, large number of steps and long cycle time of the process are likely to increase the production cost.
- the principal aspect of present invention is to provide a process for the preparation of compounds of formula I or its regioisomer comprising:
- R is CN, CI, CF 3 or OCF 3
- Another aspect of the present invention is to provide a process for the preparation of 3-(5-Nitro-4-thiocyanatopyrimidin-2-yl)-3H-benzo[ ⁇ -imidazole-5-carbomtrile of formula F or its regioisomer comprising: a) reacting 2-cMoro-5-mtro-4-thiocynatopyrimidine of formula III
- the another aspect of present invention is to provide a novel crystalline form of 3-(5- mtro-4-tIuocyanatopyrmiidm-2-yl)-3H-ben of formula characterised by a powder X-Ray diffraction pattern with peaks at 8.2458, 11.8392, 13.5188, 16.0708, 18.5858,20.6227, 22.6013, 25.1971, 26.1160, 27.4461, 29.2118, 29.9800 ⁇ 0.2 degree 2 ⁇ or substantially as indicated in figure 1.
- the present invention provides a novel crystalline form of 2-chloro- 5-nitro-4-thiocynatopyrimidine of formula III characterised by a powder X-Ray diffraction pattern with peaks at 13.0331, 15.3155, 17.5391, 18.4681, 19.8312, 22.1566, 23.7623, 24.4220, 24.8680, 26.7441, 29.0966, 30.1861, 31.6524, 32.7384, 33.9821, 37.2005 ⁇ 0.2 degree 2 ⁇ or substantially as indicated in figure 2.
- Fig 2 XRD of 2-chloro-5-nitro-4-thiocynatopyrimidine of the present invention.
- the compounds of formula V in step (a) is prepared by reacting 2-clUoro-5-nitro-4-thiocynatopyrimidine of formula III with compounds of formula IV in the presence of a suitable base and an organic solvent.
- the base is selected from the group consisting of sodium hydroxide, potassium hydroxide, sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, potassium tert- butoxide, tri ethyl amine, diisopropyl amine and the like; preferably potassium carbonate.
- the organic solvent for the above reaction is selected from the group consisting of ketonic solvents such as acetone, ethylmethyl ketone, methyl isobutyl ketone and the like; ether solvents such as diethyl ether, dimethyl ether, di-isoopropyl ether, methyltertiarybutyl ether, tetrahydrofuran, 1,4-dioxane and the like; hydrocarbon solvents such as toluene, xylene and the like; nitrile solvents such as acetonitrile, propionitrile and the like; halogenated solvents such as dichloromethane, chloroform, carbon tetrachloride and the like; aprotic polar solvents such as dimethylsulfoxide (DMSO), ⁇ , ⁇ -dimethylformamide (DMF), N,N- dimethylacetamide and the like; or mixtures thereof; preferably acetonitrile.
- ketonic solvents such as
- the compounds of formula IV is reacted with 2- cUoro-5-mtro-4-tlnocynatopyrimidme of formula III without protecting the compound of formula IV, which reduces the number of steps by two and makes the process concise and more cost effective.
- the traces of compounds of formula V(a) also forms as a regioisomer along with the desired compound of formula V.
- the desired compound is separated from the corresponding regioisomer by column chromatography or by solvent extraction.
- the compound of formula V is reacted with triethyl orthoformate or formic acid in the presence of an organic solvent selected from group of consisting of methanol, ethanol, n-propanol, isobutanol, ethyl acetate, methyl acetate, isopropyl acetate, dimethylformamide, dimethyl sulfoxide, dimethylacetamide, preferably ethanol to obtain compound of formula I or its regioisomer.
- an organic solvent selected from group of consisting of methanol, ethanol, n-propanol, isobutanol, ethyl acetate, methyl acetate, isopropyl acetate, dimethylformamide, dimethyl sulfoxide, dimethylacetamide, preferably ethanol to obtain compound of formula I or its regioisomer.
- 2-chloro-5-nitro-4- tmocynatopyrimidine of formula ⁇ is reacted with 3,4-diaminobenzonitrile of formula IV in the presence of a base preferably potassium carbonate and an organic solvent preferably acetonitrile in step (a) to obtain 3-(5-nitro-4-thiocyanato-pyrimidin-2-yl amino)-4-amino benzonitrile of formula V.
- 2-cMoro-5-nitro-4-tluocynatopyrimidine of formula III, used in step (a) is prepared by reacting 2,4-Dichloro-5-nitro-pyrimidine and potassium thiocyanate (KSCN)in acetic acid.
- KSCN potassium thiocyanate
- this invention provides novel crystalline form of 3-(5-nitro-4- tmocyanatopyrinndm-2-yl)-3H-benzo ⁇ of formula F characterised by a powder X-Ray diffraction pattern with peaks at 8.2458, 11.8392, 13.5188, 16.0708, 18.5858,20.6227, 22.6013, 25.1971, 26.1160, 27.4461, 29.2118, 29.9800 ⁇ 0.2 degree 2 ⁇ or substantially as indicated in figure 1, which is highly stable and most suitable for the synthesis of immunosuppressive agents, 8-substituted-2-benzimidazolyl purine.
- the present invention provides a novel crystalline form of 2-chloro- 5-nitro-4-tIuocynatopyrimidine of formula III characterised by a powder X-Ray diffraction pattern with peaks at 13.0331, 15.3155, 17.5391 , 18.4681, 19.8312, 22.1566, 23.7623, 24.4220, 24.8680, 26.7441, 29.0966, 30.1861, 31.6524, 32.7384, 33.9821, 37.2005 ⁇ 0.2 degree 2 ⁇ or substantially as indicated in figure 2, which has high purity and greater thermal stability.
- 2,4-DicUoro-5-nilro-pyrimidine (48 g) was dissolved in acetic acid (2L) and the reaction mixture was cooled to 0°C. Then potassium thiocyanate (25.2) was added portion wise to the reaction mixture and stirred for 2 hours, diluted with water and filtered. Then the solid was washed with water and ether to give the title compound (38 g).
- Example 2 Preparation of 3-(5-Nitro-4-thiocvanato-pyrimidin-2-yl-amino)-4-amino benzonitrile 2- cMoro-5-rntro-4-tInocynatopyrimidine(1.62 g) obtained above was reacted with 3,4- diaminobenzonitrile (1.0 g) in presence of potassium carbonate (3.1 g) and dry acetonitrile (20 mL). The reaction mass was stirred at room temperature for 3 hours and water (5 mL) was added to it.
- reaction mass was extracted with ethyl acetate to give the title compound (0.5 g) along with traces of regioisomer [4-(5-mtro-4-tluocynato-pyrimidin-2-yl- amino)-4-amino benzonitrile].
- the desired compound was separated from its regioisomer by column chromatography.
Abstract
The present invention is directed to a novel, facile, concise, industrially viable and cost effective process for the preparation of (5-Nitro-4-thiocyanate pyrimidinl)-3H-benzo(d)- imidazolyl-5-carbonitrile a compound of formula (I).
Description
A PROCESS FOR THE PREPARATION OF
5-SUBSTITUTED 3-(5-NITRO-4-TfflOCYANATOPYMMH)IN-2-YL)- 3H-BENZO [rfJ-IMTOAZOLE
FIELD OF THE INVENTION
The present invention relates to a novel, facile, industrially viable and cost effective process for manufacturing 5-substituted 3-(5-Nitro-4-thiocyanatopyrimidin-2-yl)-3H- benzo[i ]-imidazole, which is an intermediate for the synthesis of immunosuppressive agents, 8-substituted-2-benzimidazolyl purine.
BACKGROUND OF THE INVENTION
5-substituted 3-(5-Nitro-4-trdocyanatopyrimidin-2-yl)-3H-benzo[^-imidazole of formula I are intermediates for the synthesis of 8-substituted-2-benzimidazolyl purine derivatives, commonly used as immunosuppressive agents. Immunosuppression is an important clinical approach in treating autoimmune disease and in preventing organ and tissue rejection.
I
Where R is CN, CI, CF3 or OCF3
US 20080085898 Al discloses the preparation of compounds of formula I comprising condensation of protected compounds of formula IV(a) with the compounds of formula III to obtain compounds of formula V(a). The compounds of formula V(a) are hydrolysed to obtain compounds of formula V and these are further reacted in-situ with trimethyl ortho formate to obtain compounds of formula I as shown below in scheme 1.
-1
A drawback of the process reported in the above patent or in other including WO2008043019, is that the above class of compounds are synthesized from the corresponding 4-substituted 2-nitrobenzenamine by a six stage process, which involves protection, deprotection and reduction sequences that are likely to yield unwanted side products. Moreover, large number of steps and long cycle time of the process are likely to increase the production cost.
In J.Org.Chem-2006, 71, 8324-8327, similar transformations have been reported with appropriately substituted benzimidazoles in presence of pyrimidine ligands and TBAF. The method however, suffers from the limitations that it requires preparation and screening of suitable ligands and employs fairly high temperatures (145-150°C), which may not be conductive to the stability of these compounds.
In view of the above limitations, there is a continued need for developing a new cost effective and industrially viable process.
SUMMARY OF THE INVENTION
The principal aspect of present invention is to provide a process for the preparation of compounds of formula I or its regioisomer comprising:
a) reacting compound of formula IV with 2-cUoro-5-nitro-4-thiocynatopyrimidine of formula III to obtain compounds of formula V; and
b) reacting compound of formula V with triethyl orthoformate or formic acid to obtain compound of formula I or its regioisomer as given in below scheme 2.
Scheme-2
CH(OEt)3
EtOH
+ Regioisomer (<3%)
Where R is CN, CI, CF3 or OCF3
Another aspect of the present invention is to provide a process for the preparation of 3-(5-Nitro-4-thiocyanatopyrimidin-2-yl)-3H-benzo[^-imidazole-5-carbomtrile of formula F or its regioisomer comprising:
a) reacting 2-cMoro-5-mtro-4-thiocynatopyrimidine of formula III
IV to give 3-(5-mtro-4-thiocyanato-pyrimidin-2-yl amino)-4-amino benzonitrile of formula V; and
b) reacting 3-(5-nitro-4-thiocyanato-pyrimidin-2-yl amino)-4-amino benzonitrile of formula V with triethyl orthoformate or formic acid in the presence of an organic solvent to give 3-(5-nitro-4-thiocyanatopyrimidin-2-yl)-3H-benzo[i/]-imidazole-5-carbonitrile of formula
Γ or its regioisomer.
The another aspect of present invention is to provide a novel crystalline form of 3-(5- mtro-4-tIuocyanatopyrmiidm-2-yl)-3H-ben of formula characterised by a powder X-Ray diffraction pattern with peaks at 8.2458, 11.8392, 13.5188, 16.0708, 18.5858,20.6227, 22.6013, 25.1971, 26.1160, 27.4461, 29.2118, 29.9800 ± 0.2 degree 2Θ or substantially as indicated in figure 1.
In yet another aspect, the present invention provides a novel crystalline form of 2-chloro- 5-nitro-4-thiocynatopyrimidine of formula III characterised by a powder X-Ray diffraction pattern with peaks at 13.0331, 15.3155, 17.5391, 18.4681, 19.8312, 22.1566, 23.7623, 24.4220, 24.8680, 26.7441, 29.0966, 30.1861, 31.6524, 32.7384, 33.9821, 37.2005 ± 0.2 degree 2Θ or substantially as indicated in figure 2.
BRIEF DESCRIPTION OF THE ACCOMPANYING DRAWINGS
Fig 1 : XRD of 3-(5-nitro-4-tlnocyanatopyrimidm-2-yl)-3H-ben^
of the present invention.
Fig 2: XRD of 2-chloro-5-nitro-4-thiocynatopyrimidine of the present invention.
DETAILED DESCRIPTION OF THE INVENTION
In an embodiment of the present invention, the compounds of formula V in step (a) is prepared by reacting 2-clUoro-5-nitro-4-thiocynatopyrimidine of formula III with compounds of formula IV in the presence of a suitable base and an organic solvent. The base is selected from the group consisting of sodium hydroxide, potassium hydroxide, sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, potassium tert- butoxide, tri ethyl amine, diisopropyl amine and the like; preferably potassium carbonate. The organic solvent for the above reaction is selected from the group consisting of ketonic solvents such as acetone, ethylmethyl ketone, methyl isobutyl ketone and the like; ether solvents such as diethyl ether, dimethyl ether, di-isoopropyl ether, methyltertiarybutyl ether, tetrahydrofuran, 1,4-dioxane and the like; hydrocarbon solvents such as toluene, xylene and the like; nitrile solvents such as acetonitrile, propionitrile and the like; halogenated solvents
such as dichloromethane, chloroform, carbon tetrachloride and the like; aprotic polar solvents such as dimethylsulfoxide (DMSO), Ν,Ν-dimethylformamide (DMF), N,N- dimethylacetamide and the like; or mixtures thereof; preferably acetonitrile.
In another embodiment of the invention the compounds of formula IV is reacted with 2- cUoro-5-mtro-4-tlnocynatopyrimidme of formula III without protecting the compound of formula IV, which reduces the number of steps by two and makes the process concise and more cost effective.
In another embodiment of the present invention, during the reaction in step (a) the traces of compounds of formula V(a) also forms as a regioisomer along with the desired compound of formula V. The desired compound is separated from the corresponding regioisomer by column chromatography or by solvent extraction.
In another embodiment of the present invention, the compound of formula V is reacted with triethyl orthoformate or formic acid in the presence of an organic solvent selected from group of consisting of methanol, ethanol, n-propanol, isobutanol, ethyl acetate, methyl acetate, isopropyl acetate, dimethylformamide, dimethyl sulfoxide, dimethylacetamide, preferably ethanol to obtain compound of formula I or its regioisomer.
In the preferred embodiment of the invention, 2-chloro-5-nitro-4- tmocynatopyrimidine of formula ΠΙ is reacted with 3,4-diaminobenzonitrile of formula IV in the presence of a base preferably potassium carbonate and an organic solvent preferably acetonitrile in step (a) to obtain 3-(5-nitro-4-thiocyanato-pyrimidin-2-yl amino)-4-amino benzonitrile of formula V. Thus obtained 3-(5-nitro-4-thiocyanato-pyrimidin-2-yl amino)- 4-amino benzonitrile is reacted with triethyl orthoformate or formic acid in the presence of an organic solvent, preferably ethanol to give 3-(5-nitro-4-thiocyanatopyrimidin-2-yl)-3H- benzo[i/]-imidazole-5-carbonitrile-5 of formula F or its regioisomer.
In another embodiment, 2-cMoro-5-nitro-4-tluocynatopyrimidine of formula III, used in step (a) is prepared by reacting 2,4-Dichloro-5-nitro-pyrimidine and potassium thiocyanate (KSCN)in acetic acid.
In yet another embodiment, this invention provides novel crystalline form of 3-(5-nitro-4-
tmocyanatopyrinndm-2-yl)-3H-benzo^ of formula F characterised by a powder X-Ray diffraction pattern with peaks at 8.2458, 11.8392, 13.5188, 16.0708, 18.5858,20.6227, 22.6013, 25.1971, 26.1160, 27.4461, 29.2118, 29.9800 ± 0.2 degree 2Θ or substantially as indicated in figure 1, which is highly stable and most suitable for the synthesis of immunosuppressive agents, 8-substituted-2-benzimidazolyl purine.
In yet another aspect, the present invention provides a novel crystalline form of 2-chloro- 5-nitro-4-tIuocynatopyrimidine of formula III characterised by a powder X-Ray diffraction pattern with peaks at 13.0331, 15.3155, 17.5391 , 18.4681, 19.8312, 22.1566, 23.7623, 24.4220, 24.8680, 26.7441, 29.0966, 30.1861, 31.6524, 32.7384, 33.9821, 37.2005 ± 0.2 degree 2Θ or substantially as indicated in figure 2, which has high purity and greater thermal stability.
Having thus described the invention with reference to the preferred embodiments and illustrative examples, those skilled in the art would appreciate modifications to the invention as described and illustrated by the scheme and examples that do not depart from the spirit and scope of the invention as disclosed in the specification.
The examples are provided to illustrate particular aspect of the disclosure and do not limit the scope of the present invention as defined by the claims.
EXAMPLES:
Example 1: Preparation of 2-Chloro-5-nitro-4-thiocvnatopyrimidine
2,4-DicUoro-5-nilro-pyrimidine (48 g) was dissolved in acetic acid (2L) and the reaction mixture was cooled to 0°C. Then potassium thiocyanate (25.2) was added portion wise to the reaction mixture and stirred for 2 hours, diluted with water and filtered. Then the solid was washed with water and ether to give the title compound (38 g).
Spectral data
Ή NMR: d 9.389 (s, 1H) ppm; MS (ESI+) m/z: 216.1; IR: 3039.99 cm"1, 2173.26 cm"1, 1577.05 cm"1, 1530.53 cm"1 , 1375.76 cm"1 , 1348.84 cm"1 ,1316.39 cm'1 , 1211.24cm"1 , 1175.50 cm"1 ,1076.73 cm"1 , 870.02cm"1 , 772.69cm"1 , 689.45cm"1 .
Example 2: Preparation of 3-(5-Nitro-4-thiocvanato-pyrimidin-2-yl-amino)-4-amino benzonitrile
2- cMoro-5-rntro-4-tInocynatopyrimidine(1.62 g) obtained above was reacted with 3,4- diaminobenzonitrile (1.0 g) in presence of potassium carbonate (3.1 g) and dry acetonitrile (20 mL). The reaction mass was stirred at room temperature for 3 hours and water (5 mL) was added to it. The reaction mass was extracted with ethyl acetate to give the title compound (0.5 g) along with traces of regioisomer [4-(5-mtro-4-tluocynato-pyrimidin-2-yl- amino)-4-amino benzonitrile]. The desired compound was separated from its regioisomer by column chromatography.
Spectral data
1H NMR: d 10.486 (s, 1H), 9.234 - 9.147 ( d, 1H), 7.694-7.330 (m, 2H), 6.792-6.763 (d, 1H), 6.149-6.077 (d, 2H) ppm; MS (ESI+) m/z: 313.41.
Example 3; Preparation of 3-(5-Nitro-4-thiocvnatopyrimidin-2-yl)-3H-beiizo[</l- imidazole-5-carbonitrile
3- (5-Nitro-4-thiocyanato pyrimidin-2-yl amino)-4-amino benzonitrile (500 mg) as above prepared was added to triethylorthoformate (8 mL) and ethanol (8 mL). The reaction mass was stirred for 16 hour at room temperature and filtered to give the titled compound (0.395 mg).
Spectral data
1H NMR: d 9.265-9.233 (m, 2H), 9.136-9.133 (d, 1H), 7.942-7.879 (d, 1H), 7.817-7.790 (d,lH) ppm. MS (ESI+) m/z: 329.39; IR: 2230.34 cm ',2171.97 cm"1, 1560.53 cm"1, 1556.43 cm"1, 1458.32 cm"1, 1324.48 cm"1, 1198.56 cm"1, 788.25 cm"1, 693.32 cm"1, 610.99 cm"1
Claims
1. A process for the preparation of compounds of formula I or its regioisomer
I I
Where R is CN, CI, CF3 or OCF3, comprising:
a) reacting compound of formula IV 
IV
with 2-cUoro-5-nitro-4-thiocynatopyrimidine to obtain compound of formula V; and
2. A process according to claim 1 wherein, the compound of formula IV is reacted with 2- cMoro-5-rutro-4-thiocynatopyrimidine in presence of a base and a solvent to obtain the compound of formula V
3. A process according to claim 2 wherein, the base is selected from the group consisting of sodium hydroxide, potassium hydroxide, sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, potassium tert-butoxide, tri ethyl amine, diisopropyl amine; and the solvent is selected from the group consisting of acetone, ethylmethyl ketone, methyl isobutyl ketone, diethyl ether, dimethyl ether, di-isoopropyl ether, methyltertiarybutyl ether, tetrahydrofuran, 1,4-dioxane, toluene, xylene, acetonitrile, propionitrile, dichloromethane, chloroform, carbon tetrachloride, dimethylsulfoxide, N,N-dimethylformamide, Ν,Ν-dimethylacetamide or the mixtures thereof.
4. A process according to claim 2 wherein, the base used is potassium carbonate and the solvent used is acetonitrile.
5. A process according to claim 5 wherein, the compound of formula V is reacted with triethyl orthoformate in presence of an alcoholic solvent selected from methanol, ethanol, propanol and butanol to obtain compound of formula I or its regioisomer.
6. A process for the preparation of 3-(5-Nitro-4-tMocyanatopyrimidin-2-yl)-3H-benzo[i ]- imidazole-5-carbonitrile of formula F comprising:
IV to obtain 3-(5-nitro-4-thiocyanato-pyrimidin-2-yl amino)-4-amino benzonitrile of formula V'; and
V b) reacting 3-(5-nitro-4-tWocyanato-pyrimidin-2-yl amino)-4-amino benzonitrile of formula V with triethyl orthoformate or formic acid in the presence of an organic solvent to obtain 3-(5-nitro-4-tluocyanatopyrmidm-2-yl)^
of formula Γ.
7. A process according to claim 6 wherein, 3,4-diaminobenzonitrile of formula IV is reacted with 2^;Woro-5-nitro-4-tlnocynatopyrimidine in presence of a base and a solvent to obtain 3-(5-mrro-4-thiocyanato-pyrimidin-2-yl amino)-4-amino benzonitrile of formula V.
8. A process according to claim 7 wherein, the base is selected from the group consisting of sodium hydroxide, potassium hydroxide, sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, potassium tert-butoxide, tri ethyl amine, diisopropyl amine; and the solvent is selected from the group consisting of acetone, ethylmethyl ketone, methyl isobutyl ketone, diethyl ether, dimethyl ether, di-isoopropyl ether, methyltertiarybutyl ether, tetrahydrofuran, 1,4-dxoxane, toluene, xylene, acetonitrile, propionitrile, dichloromethane, chloroform, carbon tetrachloride, dimethylsulfoxide, N,N-dimethylformamide, Ν,Ν-dimethylacetamide or the mixtures thereof.
9. A process according to claim 7 wherein, the base used is potassium carbonate and the solvent used is acetonitrile.
10. A process according to claim 7 wherein, 3-(5-nitro-4-tWocyanato-pyrimidin-2-yl amino)- 4-amino benzonitrile of formula V is reacted with triethyl orthoformate in presence of a solvent to obtain 3-(5-mtro-4-thiocyanatopyrimidin-2-yl)-3H-benzo[i/]-imidazole-5- carbonitrile of formula F or its regioisomer.
11. A process according to claim 11 wherein, 3-(5-nitro-4-tbiocyanato-pyrimidin-2-yl amino)-4-amino benzonitrile is reacted with triethyl orthoformate in presence of an alcoholic solvent selected from methanol, ethanol, propanol and butanol to obtain 3-(5- nitro-4-thiocyanatopyrimidm-2-yl)-3H-benzo[^-imidazole-5-carbonitrile.
12. A crystalline form of 3-(5-mtro-4-tlnocyanatopyrimidin-2-yl)-3H-berizo[i¾-imidazole-5- carbonitrile of formula F characterised by a powder X-Ray diffraction pattern with peaks at 8.2458, 11.8392,
13.5188, 16.0708, 18.5858,20.6227, 22.6013, 25.1971, 26.1160, 27.4461, 29.2118, 29.9800 ± 0.2 degree 2Θ or substantially as indicated in figure 1.
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| US20080085898A1 (en) * | 2006-10-04 | 2008-04-10 | Pharmacopeia, Inc. | 8-substituted 2-(benzimidazolyl)purine derivatives for immunosuppression |
| US20080214580A1 (en) * | 2006-10-04 | 2008-09-04 | Pharmacopeia, Inc. | 6-substituted 2-(benzimidazolyl)purine and purinone derivatives for immunosuppression |
| US20080287468A1 (en) * | 2005-04-05 | 2008-11-20 | Pharmacopeia, Inc. | Purine and imidazopyridine derivatives for immunosuppression |
| US20080287410A1 (en) * | 2004-07-08 | 2008-11-20 | Barbosa Antonio J M | Pyrimidine derivatives useful as inhibitors of pkc-theta |
-
2010
- 2010-04-01 WO PCT/IN2010/000221 patent/WO2011121597A1/en active Application Filing
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20080287410A1 (en) * | 2004-07-08 | 2008-11-20 | Barbosa Antonio J M | Pyrimidine derivatives useful as inhibitors of pkc-theta |
| US20080287468A1 (en) * | 2005-04-05 | 2008-11-20 | Pharmacopeia, Inc. | Purine and imidazopyridine derivatives for immunosuppression |
| US20080085898A1 (en) * | 2006-10-04 | 2008-04-10 | Pharmacopeia, Inc. | 8-substituted 2-(benzimidazolyl)purine derivatives for immunosuppression |
| US20080214580A1 (en) * | 2006-10-04 | 2008-09-04 | Pharmacopeia, Inc. | 6-substituted 2-(benzimidazolyl)purine and purinone derivatives for immunosuppression |
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