Field of the Invention:
The present invention relates to novel pyrimidine derivatives, its preparation and their use in the preparation of HMG-CoA reductase inhibitors.
Background of the Invention:
Pyrimidine derivatives are important intermediates in the preparation of HMG-CoA reductase inhibitors like bis[(E)-7-[4( 4-fluorophenyl)-6-isopropyl-2[ methyl (methylsulfonyl) amino] pyrimidin-5-yl](3R,5S)3,5-dihydroxyhept-6-enoic acid] calcium sah. EP 521471 disclosed the usage of pyrimidine derivative such as N-(4-(4-fluorophenyl)-5-(substituted)-6-isopropyl pyrimidin-2-yl)-N-methylmethanesulfonamide (where in substituents is either an acid, ester group, hydroxy methyl and aldehyde group) as an intermediate in the preparation of bis[(E)-7-[4( 4-fluorophenyl)-6-isopropyl-2[ methyl (methylsulfonyl) amino] pyrimidin-5-yl](3R,5S)3,5- dihydroxyhept-6-enoic acid] calcium salt. The bis[(E)-7-[4( 4-fluorophenyl)-6-isopropyl-2[ methyl (methylsulfonyl) amino] pyrimidin-5-yl](3R,5S)3,5- dihydroxyhept-6-enoic acid] calcium salt is one of the important drugs available in the market used to treat high cholesterol and related conditions, and to prevent cardiovascular disease.
The process for the preparation of ethyl 4-(4-f[uorophenyl)-6-isopropyl-2-methylsulfonyl pyrimidine-5-carboxylate is also disclosed in patents like EP 521471 and US 6579984. It seems to be that the process disclosed for the said intermediate is not suitable for the commercial scale up since over all yields are very low and it involves the usage of toxic raw material such as cyanogen chloride.
As bis[(E)-7-[4( 4-fluorophenyl)-6-isopropyl-2[ methyl (methylsulfonyl) amino] pyrimidin-5-yl](3R,5S)3,5-dihydroxyhept-6-enoic acid] calcium salt is one of the important statin compounds which are available in the market for cholesterol reduction. It is advantageous to have alternate novel pyrimidine derivative compounds which can be utilized in the preparation of N-(4-(4-fluorophenyl)-5-(substituted)-6-isopropyl pyrimidin-2-yl)-N-methylmethanesulfonamide and bis[(E)-7-[4( 4-fluorophenyl)-6-isopropyl-2[methyl (methylsulfonyl) amino] pyrimidin-5-yl](3R,5S)3,5- dihydroxyhept-6-enoic acid] calcium salt.

Hence the main objective of the present invention is to provide novel pyrimidine derivative compounds as well as process for their preparation with high yields and purity which are useful in the preparation of HMG-CoA reductase inhibitors.
Brief Description of the Invention:
The first aspect of the present invention is to provide novel pyrimidin-5-carboxamide compounds of general formula-1 represented by the following structure

where in Ri and R2 independently selected from hydrogen, straight or branched chain alkyl group, cycloalkyl or cycloalkyl with one heteroatom; aralkyl group, aryl group and also includes the above groups with one or more substituents selected from halogen, nitro and alkyl group having 1 to 4 carbon atoms.
The novel compounds of general formula-1 of the present invention are useful intermediates in the preparation of HMG-CoA reductase inhibitors such as bis[(E)-7-[4( 4-fluorophenyl)-6-isopropyl-2[ methyl (methylsulfonyl) amino] pyrimidin-5-yl](3R,5S)-3,5- dihydroxyhept-6-enoic acid] and its pharmaceutically acceptable salts.
The second aspect of the present invention is to provide 2-oxo-pyrimidin-5-carboxamide compounds of general formula-3 represented by the following structure


The present invention further relates to a process for the preparation of 2-oxo-pyrimidin-5-carboxamide compounds of general formula-3, comprises of reacting isobutyryl acetamide derivative compounds of general formula-2

with 4-fluorobenzaldehyde and urea in the presence of a suitable acid and metal salt in presence or absence of a solvent.
The third aspect of the present invention is to provide the 2-hydroxy-pyrimidin-5-carboxamide compounds of general formula-4 represented by the following structure

The invention further relates to a process for the preparation of 2-hydroxy pyrimidin-5- carboxamide compounds of general formula-4, comprises of oxidizing the 2-oxo-pyrimidin-5-carboxamide compounds of general formula-3 with a suitable oxidizing agent in presence or absence of a solvent.

The fourth aspect of the present invention is to provide the 2-sulfonyl pyrimidin-5-carboxamide compounds of general fonnula-5 represented by the following structure

wherein Ri & R2 are as defined above; and R is selected from straight or branched chain alkyl group, cycloalkyl or cycloalkyi with one heteroatom; aralkyl group, aryl group and also includes the above groups with one or more substituents selected from halogen, nitro and alkyl group having 1 to 4 carbon atoms.
The invention further relates to the preparation of 2-sulfonyl pyrimidin-5-carboxamide compound of general formula-5, which comprise of reacting the 2-hydroxy pyrimidin-5- carboxamide compounds of general formula-4 with an organic sulfonyl halide having the following formula RSO2X
wherein R is defined as above and X is halogen
or an organic sulfonic anhydride having the following formula
(RS02)20
wherein R is defined as above;
in presence of a suitable base and a solvent.
The fifth aspect of the present invention is to provide a process for the preparation of pyrimidin-5-carboxamide compounds of general formula-1, which comprise of reacting the 2-sulfonyl pyrimidin-5-carboxamide compounds of general formula-5 with N-methyl methane sulfonamide in presence of a suitable base and a solvent.
The sixth aspect of the present invention is to provide a process for the preparation of isobutyryl acetamide compounds of general formula-2, comprise of

reacting the alkyl-4-methyl-3-oxopentanoate compounds of general formula-6 with amide compound of general formula-7 (NR1R2) in a suitable solvent and with out usage of a base.
Detailed Description of the Invention:
Accordingly the present invention provides pyrimidine derivative compounds, process for their preparation and use in the preparation of HMG-CoA reductase inhibitors such as bis[(E)-7-[4( 4-fluorophenyl)-6-isopropyl-2[ methyl (methylsulfonyl) amino] pyrimidin-5-yl](3R,5S)3,5- dihydroxyhept-6-enoic acid] calcium salt.
As used herein the term Ri and R2 refers to independently hydrogen, straight or branched chain alkyl group, cycloalkyl or cycloalkyl with one heteroatom; aralkyl group, aryl group and also includes the above groups with one or more substituents selected from halogen, nitro and alkyl group having 1 to 4 carbon atoms.
As used herein the term R refers to straight or branched chain alkyl group, cycloalkyl or cycloalkyl with one heteroatom; aralkyl group, aryl group and also includes the above groups with one or more substituents selected from halogen, nitro and alkyl group having 1 to 4 carbon atoms.
As used herein the term R' refers to CMO straight or branched chain alkyl groups.
As used herein the term "inorganic acid" refers to hydrochloric acid, sulfuric acid, nitric acid or phosphoric acid or mixtures thereof;
As used herein the term "organic acid" refers to methane sulfonic acid, ethane sulfonic acid, benzene sulfonic acid, p-toluene sulfonic acid, p-bromobenzene sulfonic acid, acetic acid, propionic acid, butyric acid, benzoic acid or mixtures thereof;
As used herein the term "metal salt" refers to copper(I)chloride, copper (Il)chloride, copper(II)acetate, iron(II)chloride, aluminium chloride, nickel (Il)bromide, tin(IV)chloride, magnesium bromide or combination thereof;

As used herein the term "inorganic base" refers to alkali metal hydroxides such as sodium hydroxide, potassium hydroxide, lithium hydroxide; alkali metal carbonates such as sodium carbonate, potassium carbonate and bicarbonates such as sodiumbicarbonate and potassiumbicarbonate; alkali metal oxides such as sodium methoxide, potassium methoxide, sodiumtertiary butoxide, potassium tertiary butoxide or mixtures thereof;
As used herein the term "alcohol solvents" refers to methanol, ethanol, isopropanol, butanol, t-butaol; the term "ethers" refers to diethyl ether, diisopropylether, tetrahydrofuran and dimethoxyethane; the term "nitrile solvents" refers to acetonitrile, propionitrile, butyronitrile and isobutyronitrile; the term "chloro solvents" refers to methylene chloride, dichloroethane, chloroform, carbontetrachloride and chlorobenzene; the term "hydrocarbon solvents" refers to benzene, toluene, xylene, heptane, hexane and cyclohexane; the term "polar aprotic solvents" refers to dimethylsulfoxide, dimethylacetamide and dimethyl formamide; and also includes the mixture of above defined solvents.
The first aspect of the present invention provides novel pyrimidin-5-carboxamide compounds of general formula-1 represented by the following structure,

where in Ri and R2 are independently selected from hydrogen, straight or branched chain alkyl group, cycloalkyl or cycloalkyl with one heteroatom; aralkyl group, aryl group and also includes the above groups with one or more substituents selected from halogen, nitro and alkyl group having 1 to 4 carbon atoms.
The novel pyrimidin-5-carboxamide compounds of general formula-1 of the present invention were useful as intermediate in the preparation of HMG-CoA reductase

inhibitors such as bis[(E)-7-[4( 4-fluorophenyl)-6-isopropyl-2[ methyl (methylsulfonyl) amino] pyrimidin-5-yl](3R,5S)3,5-dihydroxyhept-6-enoic acid] or in the preparation of pyrimidine intermediates like N-(4-(4-fluorophenyl)-5-(substituted)-6-isopropyl pyrimidin-2-yl)-N-methylmethane sulfonamide intermediate used in the preparation of bis[(E)-7-[4( 4-fluorophenyl)-6-isopropyl-2[ methyl (methylsulfonyl) amino] pyrimidin-5-yl](3R,5S)3,5- dihydroxyhept-6-enoic acid] (where in substituents is either an acid, ester group, hydroxy methyl and aldehyde group).
The second aspect of the present invention provides the 2-oxo-pyrimidin-5-carboxamide compounds of general formula-3 represented by the following structure

wherein Ri & R2 are as defined above,
with 4-flurobenzaldehyde and urea in the presence of an acid and metal salt.
The acid used is either organic or inorganic acid and the reaction can be performed in the presence or absence of a solvent. The solvents which can be used is selected from alcohols, nitriles, chloro solvents, hydrocarbon and ethers or mixtures

thereof, preferably the reaction is carried out in presence alcohol solvent. The reaction can be carried out at a suitable temperature ranges from -5 to 200°C, preferably 25 to 120'^C. The 2-oxo-pyrimidin-5-carboxamide compounds of general formula-3 obtained can be isolated and can be purified by the conventional procedures such as distillation, crystallization and recrystallisation.
The third aspect of the present invention provides the 2-hydroxy-pyrimidin-5-carboxamide compounds of general formula-4 represented by the following structure

wherein Ri & R2 are as defined above,
The invention further provides a process for the preparation of 2-hydroxy-pyrimidin-5-carboxamide compounds of general formula-4, which comprise of oxidizing the 2-oxo-pyrimidin-5-carboxamide compounds of general formula-3

in presence of a suitable oxidizing agent like nitric acid in presence or absence of a solvent at suitable temperature ranges from 0 to 80°C. The nitric acid can be employed in an amount of 1 to 25 moles, preferably 2 to 15 moles per one mole of compounds of

general fonnula-3; preferably the reaction is carried out in absence of solvent. The reaction initiator such as sodium nitrite may also be utilized to accelerate the oxidation rate. The resulting product can be isolated and purified by the conventional methods known in the art.
The fourth aspect of the present invention provides the 2-sulfonyl pyrimidin-5-carboxamide compounds of general formula-5 represented by the following structure

wherein Ri & R2 are as defined above; and R is selected from straight or branched chain alkyl group, cycloalkyl or cycloalkyl with one heteroatom; aralkyl group, aryl group and also includes the above groups with one or more substituents selected from halogen, nitro and alkyl group having 1 to 4 carbon atoms.
The present invention further provides a preparation of 2-sulfonyl pyrimidin-5-carboxamide compounds of general formula-5, which comprise of reacting the compounds of general formula-4
F

with an organic sulfonyl halide having the following formula RSO2X

where in R is defined as above and X is halogen
or organic sulfonic anhydride having the following formula
(RS02)20
wherein R is defined above;
in presence of a suitable base selected from inorganic or organic base, preferably inorganic base and a suitable solvent selected esters, alcohols, nitriles, chloro solvents, hydrocarbon and ethers or mixtures thereof, preferably ester solvent provides the compounds of general formula-5. The reaction mixtiire was carried out at a temperature in the range of-25 to 200°C.
The 2-sulfonyl pyrimidin-5-carboxamide compoimds of general formula-5 can be isolated as solid and purified using conventional methods known in the art. The 2-hydroxy-pyrimidin-5-carboxamide compounds of general formula-4 may also convert directly into to pyrimidin-5-carboxamide compounds of general formula-1 with out isolation or purification of 2-sulfonyl pyrimidin-5-carboxamide compounds of general formula-5.
For example, the organic sulfonyl halides used in the present invention may be selected from methanesulfonyl fluoride, methanesulfonyl chloride, ethanesulfonyl chloride, 1-propanesulfonyl chloride, 2-propanesulfonyl chloride, trifluoro methanesulfonyl fluoride, trifluoromethanesulfonyl chloride, benzenesulfonyl chloride, Inaphthalenesulfonyl chloride, 2-naphthalenesulfonyl chloride, p-toluenesulfonyl fluoride, p-toluenesulfonyl chloride, 2,4, 6-trimethylbenzenesulfonyl chloride, 2,4, 6-triisopropylbenzenesulfonyl chloride, p-methoxybenzenesulfonyl chloride, p-chloro benzenesulfonyl chloride and 2-nitrobenzenesulfonyl chloride.
For example, the organic sulfonyl anhydrides used in the present invention may be selected from methanesulfonic anhydride, trifluoromethanesulfonic anhydride, benzenesulfonic anhydride, and p-toluenesulfonic anhydride.
The fifth aspect of the present invention provides a process for the preparation of pyrimidin-5-carboxamide compounds of general formula-1,


which comprise of reacting the 2-sulfonyl pyriinidin-5-carboxamide compounds of general formula-5

with N-methyl methane sulfonamide in presence of a suitable base selected from organic or inorganic base; preferably inorganic base and in a suitable solvent selected from esters, alcohols, nitriles, chloro solvents, hydrocarbon and ethers or mixtures thereof, preferably hydrocarbon solvent, to provide the pyrimidin-5-carboxamide compounds of general formula-1.
The obtained compounds of general formula-1 can be isolated and purified as per the process known in the art.
The sixth aspect of the present invention provides a process for the preparation of isobutyryl acetamide derivative compounds of general formula-2.


which comprise of reacting the alkyl-4-methyl-3-oxopentanoate compounds of general formula-6

wherein Ri«& R2 are as defined above;
in presence of a suitable polar aprotic solvent and without usage of a base at suitable temperature ranges from 30 to 100°C, preferably 70-80°C to provide the isobutyryl acetamide derivative compounds of general formula-2.
As per the prior art, the isobutyryl acetamide derivative compounds of general formula-2 (wherein R1&R2 are ethyl) prepared in presence of a DMAP and a solvent and obtained as a oily compound after purified by radial chromatography. The present invention avoids the usage of chromatographic techniques, and also conducts the reaction in absence of solvent and DMAP.
Further the pyrimidine derivatives compounds of formula-1, 3, 4 and 5 of present invention were novel compounds, which were useful as intermediates in the preparation of HMG-CoA reductase inhibitors such as bis[(E)-7-[4( 4-fluorophenyl)-6-isopropyl-2[ methyl (methylsulfonyl) amino] pyrimidin-5-yl](3R,5S)3,5- dihydroxyhept-6-enoic acid] or in the preparation of other pyrimidine derivatives such as N-(4-(4-fluorophenyl)-5-(substituted)-6-isopropylpyrimidin-2-yl)-N-methylmethane sulfonamide used in the preparation of bis[(E)-7-[4( 4-fluorophenyl)-6-isopropyl-2[ methyl (methylsulfonyl) amino] pyrimidin-5-yl](3R,5S)3,5- dihydroxyhept-6-enoic acid] calcium salt.
The novel pyrimidine derivative compounds such as pyrimidin-5-carboxamide compounds of general formula-1, 2-oxo-pyrimidin-5-carboxamide compounds of general

fonnula-3, 2-hydroxy-pyrimidin-5-carboxamide compounds of general fonnula-4 and 2-sulfonyl pyrimidin-5-carboxamide compounds of general formula-5 used an important intermediates in the preparation of other pyrimidine derivatives and the same also be converted into bis[(E)-7-[4( 4-fluorophenyl)-6-isopropyl-2[ methyl (methylsulfonyl) amino] pyrimidin-5-yl](3R,5S)3,5- dihydroxyhept-6-enoic acid] or its pharmaceutically acceptable salt. The use of novel pyrimidine derivative compounds of formula-1, 3, 4 & 5 of the present invention shown by the following schematic representation


In a preferred embodiment of the present invention, Ri & R2 is ethyl group, R' is methyl group and R is p-toluene.
In a preferred embodiment, the present invention provides the following compound of formula-la

Further the present invention provides a process for the preparation of N,N-diethyl-4-(4-fluorophenyl)-6-isopropyl-2-(N-methyl methane sulfonamido) pyrimidine-5-carboxamide compound of formula-1 a, which comprises of the following steps; a) Reacting the methyl-4-methyl-3-oxopentanoate compound of formula-6a


b) reacting the N,N-diethyl-4-methyl-3-oxopentanamide compound of formula-2a with
4-flurobenzaldehyde and urea in the presence of an organic or inorganic acid and
metal salt in presence of a suitable solvent selected from alcohols, nitriles, chloro
solvents, hydrocarbon and ethers or mixtures thereof, to provide the N,N-diethyl-4-
(4-fluorophenyl)-6-isopropyl-2-oxo-l,2,3,4-tetrahydropyrimidine-5-carboxamide
compound of formula-3a,

c) oxidizing the compound of formuala-3a with nitric acid provides the N,N-diethyl-4-
(4-fluorophenyl)-2-hydroxy-6-isopropylpyrimidine-5-carboxamide compound of
formula-4a,

d) reacting the compound of formula-4a with an paratoluene sulfonyl chloride in
presence of a suitable inorganic or organic base in a suitable solvent selected esters,
alcohols, nitriles, chloro solvents or mixtures thereof provides the 5-(diethyl
carbamoyl)-4-(4-fluorophenyl)-6-isopropylpyrimidin-2-yl-4-methyl benzene
sulfonate compound of formula-5a,


e) reacting the compound of formula-5a with N-methyl methane sulfonamide in presence of a suitable organic or inorganic base in a suitable solvent selected from esters, alcohols, nitriles, chloro solvents, hydrocarbon and ethers or mixtures thereof, provides the compound of formula-la.

The process described in the present invention was demonstrated in examples illustrated below. These examples are provided as illustration only and therefore should not be construed as limitation of the scope of the invention.
Examples:
ExampIe-1: Preparation of N,N-diethyl-4-methyl-3-oxopeiitananiide of forinuIa-2a:
Mixture of methyl-4-methyl-3-oxopentanoate (100 grams) and diethyl amine (100 grams) in dimethyl sulfoxide (100 ml) was heated to reflux temperature and stirred, till the completion of the reaction. Diethylamine was distilled off completely imder reduced pressure at below 80°C and then cooled to RT. The reaction mixture was quenched with water and then extracted into ethyl acetate. Ethyl acetate layer was dried over sodium sulfate and distilled off ethyl acetate completely under reduced pressure to get the title compound. Yield: 120 grams
£xample-2: Preparation of N,N-diethyl-4-(4-fluorophenyl)-6-isopropyl-2-oxo-l,23)4-tetrahydropyrimidine-5-carboxamide of formula-3a:
A mixture of N,N-diethyl-4-methyl-3-oxopentanamide (110 grams),4-fluoro benzaldehyde (81.1 ml), urea (68.8 grams), copper(I)chloride (0.88 ml), sulfuric acid (8.8 ml) and methanol (550 ml) was heated to reflux temperature and stirred upto the completion of the reaction. The solvent from the reaction mixture was completely distilled off under reduced pressure and water (1100 ml) was added to it. The reaction mixture was stirred for 90 minutes at 25-30°C, filtered the obtained solid, washed with water followed by cyclohexane and then dried to get the title compound. Yield: 175 grams Melting Range: 157-168^0
Example-3: Preparation of N,N-diethyl-4-(4-fluorophenyl)-2-hydroxy-6-isopropyl pyrimidine-5-carboxamide of formula-4a:
N,N-diethyl-4-(4-fluorophenyl)-6-isopropyl-2-oxo-l,2,3,4-tetrahydropyrimidine-5*carboxamide (40 grams) was added to a pre cooled mixture of nitric acid (80 grams)

and sodium nitrite (0.33 grams) at 5 to 10°C. The reaction temperature was raised to 25-35°C and stirred up to the completion of the reaction. The reaction mixture was cooled to 10°C and water(266 ml), followed by acetic acid (20 ml) was added to it. The reaction mixture was basifled with aqueous sodium hydroxide and stirred for 3 hours. The solid formed was filtered, washed with water and dried to get the title compound. Yield: 36.2 grams Melting Range: 198-208°C
ExampIe-4: Preparation of 5-(diethylcarbamoyl)-4-(4-fluorophenyl)-6-isopropyI pyrimidin-2-yl-4-inethyl benzene sulfonate of formula-5a:
Paratoluene sulfonyl chloride (58,5 grams) was added to a mixture of N,N-diethyl-4-(4-fluorophenyl)-2-hydroxy-6-isopropyl pyrimidine-5-carboxamide (85 grams), potassium carbonate (53,4 grams) in ethyl acetate (425 ml) at 25-35°C, heated to reflux and stirred up to completion of the reaction. The reaction mixture cooled and quenched with water. Aqueous and organic layers were separated and aqueous layer extracted with ethyl acetate. The total organic layer was dried with sodium sulphate and distilled off the solvent completely under reduced pressure. The obtained residue was crystallized using petroleum ether. Yield: 108 grams Melting Range: 113-118°C
Example-6: Preparation of N,N-diethyl-4-(4-fluorophenyl)-6-isopropyl-2-(N-methyl methane sulfonamido) pyrimidine-5-carboxamide of formula-la:
A mixture of 5-(diethylcarbamoyl)-4-(4-fluorophenyl)-6-isopropyl pyrimidin-2-yl-4-methyl benzene sulfonate (23 grams), potassium carbonate (16.7 grams), N-methyl methane sulfonamide (12.6 grams) in toluene (115ml) was heated to reflux and stirred at reflux under azeotropic mode upto the completion of the reaction. The reaction mixture was cooled to RT and quenched it with water. The organic and aqueous layers were separated and aqueous layer was extracted with toluene. Total organic layer was dried and distilled off imder reduced pressure. The obtained residue was crystallized from methanol. Yield: 8 grams; M.R: 138-143°C

We Claim:
1) Compounds having the following structural formulae

Wherein R, Ri and R2 independently selected from hydrogen, straight or branched chain alkyl group, cycloalkyl or cycloalkyl with one heteroatom; aralkyl group, aryl group and also includes the above groups with one or more substituents selected from halogen, nitro and alkyl group having 1 to 4 carbon atoms, provided R is not a hydrogen.



3) Use of pyrimidine derivatives compounds as claimed in claim 1 & 2 as an
intermediate or processing aid in the preparation of HMG-CoA reductase inhibitors
such as bis[(E)-7-[4( 4-fluorophenyl)-6-isopropyl-2[ methyl (methylsulfonyl) amino]
pyrimidin-5-yl](3R,5S)3,5- dihydroxyhept-6-enoic acid] and its pharmaceutically
acceptable salts or in the preparation of pyrimidine derivatives like
N-(4-(4-fluorophenyl)-5-(substituted)-6-isopropylpyrimidin-2-yl)-N-methylmethane
sulfonamide intermediates which were used in the preparation of bis[(E)-7-[4( 4-
fluorophenyl)-6-isopropyl-2[methyl (methylsulfonyl) amino] pyrimidin-5-yl](3R,5S)-
3,5- dihydroxyhept-6-enoic acid].
4) Process for the preparation of 2-oxo-pyrimidin-5-carboxamide compounds of general
formula-3,

which comprise of reacting an isobutyryl acetamide derivative compounds of general formula-2


with 4-flurobenzaldehyde and urea in the presence of an acid selected from inorganic or organic acid and a metal salt in presence or absence of a solvent, if solvent used w^hich may be selected from alcohols, nitriles, chloro solvents, hydrocarbon and ethers or mixtures thereof, provides the 2-oxo-pyrimidin-5-carboxamide compoimds of general formula-3.
5) Process for the preparation of 2-hydroxy-pyrimidin-5-carboxamide compoimds of general fonnula-4,
which comprise of oxidizing the 2-oxo-pyrimidin-5-carboxamide compounds of general formula-3
in presence of a suitable oxidizing agent like nitric acid in presence or absence of a solvent.

6) Process for the preparation of 2-sulfonyl pyrimidin-5-carboxamide compounds of general formula-5,

which comprise of reacting the 2-hydroxy-pyrimidin-5-carboxamide compounds of general formula-4
with an organic sulfonyl halide having the following formula
RSO2X
wherein R is defined as above and X is halogen
or organic sulfonic anhydride having the following formula
(RS02)20
wherein R is defined as above;
in presence of a suitable base selected from inorganic or organic base in presence of a suitable solvent selected esters, alcohols, nitriles, chloro solvents, hydrocarbon and ethers or mixtures thereof, to provide the 2-sulfonyl pyrimidin-5-carboxamide compoimds of general formula-5.

7) Process for the preparation of pyrimidin-S-carboxamide compounds of general formula-1,

which comprise of reacting the 2-sulfonyl pyrimidin-5-carboxamide compounds of general formula-5

with N-methyl methane sulfonamide in presence of a suitable base selected from organic or inorganic base, in a suitable solvent selected from esters, alcohols, nitriles, chloro solvents, hydrocarbon and ethers or mixtures thereof, to provide the pyrimidin-S-carboxamide compounds of general formula-1.
8) A process for the preparation of isobutyryl acetamide derivative compounds of general formula-2,
which comprise of reacting the alkyl-4-methyl-3-oxopentanoate compounds of general formula-6


where in Ri& R2 are as defined above;
in presence of a suitable polar aprotic solvent and without use of a base at a suitable
temperature ranges from 30 to 100°C to provide the compounds of general fonnula-2.
9) A process for the preparation of N,N-diethyl-4-(4-fluorophenyl)-6-isopropyl-2-(N-methyl methane sulfonamido) pyrimidine-5-carboxamide compound of formula-la, which comprises of the following steps;
a) Reacting the methyl-4-methyl-3-oxopentanoate compoimd of formula-6a

b) reacting the N,N-diethyl-4-methyl-3-oxopentanamide compound of formula-2
with 4-flurobenzaldehyde and urea in the presence of organic or inorganic acid

and metal salt in presence of a suitable solvent selected from alcohols, nitriles, chloro solvents, hydrocarbon and ethers or mixtures thereof, to provide the N,N-diethyl-4-(4-fluorophenyl)-6-isopropyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide compound of formula-3a,

c) oxidizing the compound of formuala-3a with nitric acid provides the N,N-diethyl-
4-(4-fluorophenyl)-2-hydroxy-6-isopropylpyrimidine-5-carboxamide compound
offormula-4a,

d) reacting the compound of fonnula-4a with an paratoluene sulfonyl chloride in
presence of a suitable inorganic or organic base in a suitable solvent selected
esters, alcohols, nitriles, chloro solvents or mixtures thereof to provide the
5-(diethylcarbamoyl)-4-(4-fluorophenyl)-6-isopropylpyrimidin-2-yl-4-methyl
benzene sulfonate compound of formula-5a.


e) reacting the compound of formula-5a with N-methyl methane sulfonamide in presence of a suitable organic or inorganic base in a suitable solvent selected from esters, alcohols, nitriles, chloro solvents, hydrocarbon and ethers or mixtures thereof, to provide the N,N-diethyl-4-(4-f[uorophenyl)-6-isopropyl-2-(N-methyl methane sulfonamide) pyrimidine-5-carboxamide compound of formula-la.
10) A process for the preparation of bis[(E)-7-[4( 4-fluorophenyl)-6-isopropyl-2[ methyl (methylsulfonyl) amino] pyrimidin-5-yl](3R,5S)3,5- dihydroxyhept-6-enoic acid] or its pharmaceutically acceptable salts thereof, which comprise of preparing the N,N-diethyl-4-(4-fluorophenyl)-6-isopropyl-2-(N-methylmethanesulfonamido) pyrimidine-5-carboxamide compound of formula-1 as per the process claimed in claim 9 and converting into bis[(E)-7-[4( 4-fluorophenyl)-6-isopropyl-2[methyl (methylsulfonyl) amino] pyrimidin-5-yl](3R,5S)3,5-dihydroxyhept-6-enoic acid] or its pharmaceutically acceptable salts thereof.