FORM 2
THE PATENT ACT, 1970
(39 of 1970)

The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10 and rule 13)

Title of the invention
"PROCESS FOR THE PREPARATION OF ROSUVASTATIN OR PHARMACEUTICALLY ACCEPTABLE
SALTS THEREOF"

Enaltec Labs Pvt. Ltd. an Indian Company, having its Registered Office at 17`hFloor, Kesar Solitaire, Plot No.5 Sector-19, Sanpada, Navi Mumbai Maharashtra, India. Pin Code: 400705

1 The following specification particularly describes the invention and the manner in which it is to be
performed.

PROCESS FOR THE PREPARATION OF ROSUVASTATIN OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF

FIELD OF THE INVENTION:

The present invention relates to a process for the preparation of rosuvastatin or pharmaceutically acceptable salts thereof

BACKGROUND OF THE INVENTION:

Rosuvastatin calcium is chemically bis [(E)-7-[4(4-flt.orophenyl)-6-isopropyl-2[methyl
(methylsulfonyl) amino] pyrimidin-5-yi] (3R, 5S) 3, 5- dihydroxyhept-6-enoic acid]
calcium salt (2:1) and is known from U.S. Patent no. 5,260,440 and is represented by structural formula I.

Ca+2

-' 2

Formula I

Rosuvastatin is an anti hypercholestero I emi c drug and is indicated in the treatment of atherosclerosis. Rosuvastatin calcium is sold under the brand name CRESTOR ®.

Rosuvastatin and a process for its preparation are disclosed in U.S.Patent no. 5,260,440.
The process disclosed therein involves four distinct chemical steps: (1) condensation of
methyl (3R)-3-[(tert-butyldimethylsilyl) oxy]-5-otto-6-triphenylphosphoranyli-dene

hexanoate with 4-(4-fluorophenyl)-b-isopropyl-2-(N-methyl-N-methanesulfonylamino)-
5-pyrimidinecarboxaldehyde; (2) deprotection of the 3-hydroxyl group to give the keto alcohol; (3) reduction of 5-oxo to get the chiral dihydroxy heptenoate; and (4) hydrolysis of the dihydroxy heptenoate. The generation of the phosphorane side chain requires eight synthetic steps and involves expensive reagents. The process is both uneconomical and time consuming, hence not suitable for commercial production.

U.S. Patent publication no. 2008/0207903 describes a process for the preparation of
rosuvastatin or a pharmaceutically acceptable salt thereof, which comprises reaction of a
compound of formula II,

Fonnula 11
wherein L is a leaving group, which includes, for example chloro, bromo, iodo, -
OSO2CF3, -0001, -SO2C1 and -C (O) O-SOZRY, wherein R" is aryl (such as phenyl) or
substituted aryl (such as tolyl) and X is a group Z which is N-(methyl)
methylsulfonylamino or X is a group Y which is a group that is capable of conversion
into the group Z,
with a compound of the formula III,

Fonnula I11

wherein A is selected from a group (i) to (vii) below,

3

OP1 OPz

0 Op3

Op4 OPS

oP9

OR4

wherein P' and P2 are independently selected from hydrogen and a hydroxy protecting
group, or P' together with P2 form a 1,3-dihydroxy protecting group;P' is hydrogen or a
hydroxy protecting group;P4 and P' are independently selected from hydrogen and a
hydroxy protecting group, or P4 together with P' form a 1,3-dihydroxy protecting group,
and P6 and P7 are independently a hydroxy protecting group; or p5 together with P6 form
a 1,3-dihydroxy protecting group, and P4 is hydrogen or a hydroxy protecting group and
P7 is a hydroxy protecting group;P8 is hydrogen or a hydroxy protecting group;P9 is
hydrogen or a hydroxy protecting group;P'0 and P" are independently selected from

4

hydrogen and a hydroxy protecting group, or pi0 together with P' I, or P" together with
R4, forma 1,3-dihydroxy protecting group; and unless otherwise stated R', R2, R3 and R4
are independently carboxy protecting groups; in the presence of a catalytically effective
amount of a palladium catalyst and in the presence of a base; followed by (a) when X is a
group Y, the group Y is converted into the group Z; followed by(b) when A is a group (i),
carrying out in any order the steps of (1) when P' is a hydroxy protecting group, removal
of the protecting group P'; (2) when P2 is a hydroxy protecting group, removal of the
protecting group P2; and (3) removal of the protecting group R';(c) when A is a group
(ii), carrying out in any order the steps of (I) asymmetric reduction of the carbonyl group
adjacent to the carbon-carbon double bond; (2) when P3 is a hydroxy protecting group,
removal of the protecting group P3; and (3) removal of the protecting group R2;(d) when
A is a group (iii), carrying out in any order the steps of (1) when P4 is a hydroxy
protecting group, removal of the protecting group P4; (2) when P5 is a hydroxy protecting
group, removal of the protecting group P'; (3) removal of the protecting group P6; and (4)
removal of the protecting group P7;(e) when A is a group (iv), carrying out in any order
the steps of (1) when Ps is a hydroxy protecting group, removal of the protecting group
Ps; (2) asymmetric hydration of the carbon-carbon double bond adjacent to the ester
group COO.R3; and (3) removal of the protecting group R3;(f) when A is a group (v),
carrying out in any order the steps of (1) when P9 is a hydroxy protecting group, removal
of the protecting group P9; and (2) hydrolysis under basic conditions.

U.S. Patent no. 7,312,329 describes a process for the preparation of pyrimidine
derivatives by the reaction of Wittig reagent of the general formula IV

Rz
R

N \ �=

R x
Z N R3
R'
Formida IV
wherein R is an alkyl of from I to 10 carbon atoms, aryl or arylalkyl, R' is a substituted
or unsubstituted hydrocarbon group, R' and R3 are the same or different and are hydrogen

5

or a substituted or unsubstituted hydrocarbon group; Z is sulfur, oxygen, sulfonyl, or
imino which may be substituted by formyl, acetyl, propionyl, butyryl, isobutyryl, valeryl,
isovaleryl, amino substituted by sulfonyl or alkylsulfonyl, and sulfonyl substituted by
alkyl, amino or alkylamino and X is a halogen; with an aldehyde of the general formula

ORS ORS 0

OHC_ v -OR4

Formula V

wherein R4 is hydrogen, a lower alkyl or a cation capable of forming a non-toxic
pharmaceutically acceptable salt and each R5 are the same or different and are hydrogen
or a hydrolyzable protecting group, or each R', together with the oxygen atom to which
each is bonded, form a hydrolyzable cyclic protecting group, or each R5 is bonded to the
same substituent which is bonded to each oxygen atom to form a hydrolyzable protecting
group; in the presence of a base to provide a pyrimidine derivative of the general formula

R2 OR5 ORS 0
n

OR4

/Z�NR'
R1

Formula VI

wherein R, Rl, R2, R3, R4, R5, X and Z have the aforestated meanings or a racemic
mixture, an enantiomer, a diastereoisomer or a mixture thereof.

PCT publication no. 2006/128954 describes a process for the preparation of N-[4-(4-
Fluorophenyl)-5-formyl-6-isopropyl-pyrimidin-2-yl]-N-methylmethanesulfonamide, a
useful intermediate for the preparation of rosuvastatin or a .pharmaceutically acceptable
salt thereof.
6

PCT publication no. 2008/044243 describes a process for the preparation of rosuvastatin calcium compound of structural formula I by basic hydrolysis of a compound of structural formula VII in an organic solvent.

Formula VII
wherein M' and.M" is independently selected from hydrogen, lower alkyl, alkyl, aryl or, aralkyl or M' and M" taken together with the linking nitrogen atom form a mono or bicyclic heterocycle which may optionally contain in all ring moieties further nitrogen, oxygen, or sulphur heteroatoms and which may optionally be substituted. Wherein M is a hydrophobic anchor or a residue of HMG-CoA reductase inhibitor.

U.S. Patent no. 6,784,171 describes a process for the preparation methyl 4 -(4-
fl uorophenyl)-6-isopropyl-2-(methyl(methylsulfonyl)amino)pyrimidine-5-carboxylate
compound of structural formula XVII comprises reacting methyl 2-amino-4-(4-
l fuorophenyl)-6-isopro yl-pyrimidine-5 -carboxyl ate compound of structural formula XVI
with methanesulfonyl chloride in presence of sodium tert-pentoxide in dimethoxyethane
solvent followed by the methylation with dimethyl sulfate.

F

0=5=0 CHI
CH3
CH,

Formula XVI Formula XVII

7

SUMMARY OF THE INVENTION:

A first aspect of the present invention is to provide a process for the preparation of
rosuvastatin or pharmaceutically acceptable salts thereof as provided below in scheme I.

R'O R20

R'
OHG

Formula IX

Formula V J11

OH

Formula X I V

Formula X

N
H,C
S/O N�

CHI

Formula XIII

Scheme I

Formula XI

N
HNC II
N t4
5`O
O° CH3

Formula XII

wherein R' and R2 are alcohol protecting groups or R' and R2 taken together, form a 1, 3-
diol protecting group, R8 is -CN, -CONH2, -CON(R9R1O), -COOR 9 or a group that is
capable of conversion into -000H [R9and R10 is independently selected from hydrogen,
alkyl, aryl, arylalkyl or R9and R1° taken together with the linking nitrogen atom form a
mono or bicyclic heterocyclic which may optionally contain in all ring moieties further
nitrogen, oxygen or sulphur heteroatom and which may optionally be substituted], X is a nitro functional group, , Y is halogen, -P(O)(C6H5)2, -S(O)2R4,
e
or P(RS)3A O
R4 is

S

R5

wherein
R5 is alkyl, aryl, arylalkyl or cycloalkyl
R6 is H, alkyl, aryl, arylalkyl, CF3, halo or NO2
R7 is H, alkyl, alkyloxy, haloalkyl, monohaloalkyloxy, dihaloalkyloxy and Z is 0, N-H, N-alkyl or S.
A is halide such as chloro or bromo
A second aspect of present invention is to provide novel intermediates such as compound of structural formula VIII and compound of structural formula X for the preparation of rosuvastatin or pharmaceutically acceptable salts thereof.

Formula VIII Formula X

wherein, X, Y, R1, R2 and RY are defined as above.
The further aspect of present invention is to provide a process for the preparation of rosuvastatin or pharmaceutically acceptable salts thereof comprising the steps of:
a. reacting a Compound of structural fonnula VIII with a compound of structural
formula IX to get a compound of structural formula X,

9

RIO_ RIO

OHC

Formula IX

Formula VIII
Formula X

b. converting a compound of structural formula X into a compound of structural
formula XI,

H2N

Fonnula X

Formula XI

c. converting a compound of structural formula XI into a compound of structural

formula XII and

H2N

Formula XI

Formula XII

d. converting a compound of structural formula XII into rosuvastatin or
pharmaceutically acceptable salts thereof.

to

DETAIL DESCRIPTION OF THE INVENTION:

The example of compound of structural formula VIII may include ((4-(4-fluorophenyl)-6-
isopropyl-2-nitropyrimidin-5-y1) methyl) triphenylphosphonium bromide compound of structural formula XVIII

02N

Formula XVIII

The compound of structural formula XVIII may be prepared by method known in the art
such as those described in U.S. Patent no. 7,312,329, which is incorporated herein by
reference only.

The reaction of a compound of structural formula VIII with a compound of structural formula IX maybe carried out in the presence of inorganic base in an aprotic solvent at a temperature in the range of 30°C to 80°C for a period of 30 minutes to 5 hours to get a compound of structural formula X.
The examples of an inorganic base may include but not limited to sodium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide, sodium bicarbonate, potassium bicarbonate, lithium hydroxide or lithium carbonate.
The examples of aprotic solvents may include but not limited to dimethylsulfoxide, dim ethylformamide, dimethylacetamide or mixture(s) thereof,

The compound of structural formula X may be isolated by diluting the reaction mixture
with an aromatic hydrocarbon solvent, followed by the washing of an organic layer with
1 1

water and concentrating under reduced pressure to get crude compound of structural
formula X.

The examples of aromatic hydrocarbon solvents may include but not limited to toluene, xylene, cresol or mixture(s) thereof.

The crude compound of structural formula X may be purified by the treatment with an alcohol solvent.

The examples of alcohol solvents may include but not limited to methanol, ethanol, n-
propanol, isopropanol, n-butanol, isobutanol, n-pentanol, isopentanol, sec-butyl alcohol, tert-butyl alcohol or mixture(s) thereof.

The compound of structural formula X may be isolated by the steps of filtration, centrifugation, washing, drying and combination thereof.
The compound of structural formula X may be dried at a temperature in the range of 40°C to 70°C under reduced pressure.
The example of compound of structural formula X may include tert-butyl 2-((4R, 6S)-6-
((E)-2-(4-(4-fluorophenyl)-6-isopropyl-2-nitropyrimidin-5-yl) vinyl)-2, 2-dimethyl-1, 3-
dioxan-4-yl) acetate compound of structural formula XIX

O2N
CH3
Formula XIX

The conversion of a compound of structural formula X into a compound of structural formula XI may be carried out by reacting compound of structural formula X with sodium dithionite in the presence of ammonia in ketone solvent to get a compound of structural formula XI.
The reaction of compound of structural formula X with sodium dithionite in the presence of ammonia may be carried out at a temperature in the range of 25°C to 50°C for a period of 30 minutes to 3 hours to get a compound of structural formula Xi.
The examples of ketone solvent may include but not limited to acetone, methyl isobutyl ketone, 2-butanone, 3-pentanone or mixture(s) thereof.

The compound of structural formula XI may be isolated by quenching the reaction mixture with an aromatic hydrocarbon solvent, followed by washing the organic layer with water and concentrating the organic layer under reduced pressure to get a compound of structural formula Xl.

The compound of structural formula XI may be purified by the crystallization in alkyl acetate solvents.
The examples of alkyl acetate solvents may include but not limited to methyl acetate, ethyl acetate, n-propyl acetate, isopropyl acetate, n-butyl acetate, isobutyl acetate or mixture(s) thereof

The example of compound of structural formula XI may include tert-butyl 2-((4R, 6S)-6-
((E)-2-(2-amino-4-(4-fluorophenyl)-6-isopropylpyrimidin-5-yl) vinyl)-2, 2-dimethyl-1, 3-
dioxan-4-yl) acetate compound of structural formula XX.

HZN
CH3
Formula XX

The conversion of a compound of structural formula XI into a compound of structural
formula XII may be carried out by reacting compound of structural formula XI with
methane sulfonyl chloride in the presence of sodium tertiary pentoxide in ether solvent at
a temperature in the range of -15°C to 35°C for a period of 20 minutes to 2 hours
followed by the reaction with a methylating agent.

The examples of methylating agent may include methyl iodide or dimethyl sulfate.

The examples of ether solvent may include but not limited to tetrahydrofuran, 2-methyl
tetrahydrofuran, 1, 4-dioxane, methyl tertiary butyl ether, diethyl ether, diisobutyl ether,
di-n-butyl ether, di-n-propyl ether, di-isopropyl ether, dimethoxyethane or mixture(s)
thereof

The compound of structural formula XII may be isolated by quenching the reaction
mixture with an aqueous solution of sodium chloride followed by isolation of organic
layer.
The organic layer containing the compound of structural formula XII may be washed with water and stirred at a temperature in the range of 0°C to 5°C for a period of 1 hour to 4 hours to get a precipitate of compound of structural formula XII.

The precipitate of compound of structural formula XIl may be filtered, washed with a mixture of water and ether solvent (50:50) and may be dried at a temperature in the range of 50°C to 70°C under reduced pressure.
The example of compound of structural formula XII may include tert-butyl 2-((4R, 6S)-
6-((E)-2-(4-(4-fluorophenyl)-6-isopropyl-2-(N-m ethyl methylsulfonamido) pyrimidin-5-
yl) vinyl)-2, 2-dimethyl-1, 3-dioxan-4-yl) acetate compound of structural formula XV.

Formula XV

The compound of structural formula XII may be converted into rosuvastatin or
pharmaceutically acceptable salts thereof by methods known in the art such as those
described in U.S Patent nos 6,784,171; 6,875,867; 7,232,920 or 7,312,329 and U.S Patent
publication no 20070155765; 20070255060; 2008207903 or 2010056783, which are
incorporated herein by reference only.

EXAMPLE:

In the following example, the preferred embodiments of the present invention are
described only by way of illustrating the process of the invention. However, these are not intended to limit the scope of the present invention in any way.

Example No. 1: Preparation of tert-butyl 2-((4R, 6S)-6-((E)-2-(4-(4-fluorophenyl)-6-
isopropyl-2-(N-methylm ethylsulfonamido) pyrimidin-5-yl) vinyl)-2, 2-dimethyl-1, 3-
dioxan-4-yl) acetate compound of structural formula XV

Stage 1: Preparation of tert-butyl 2-((4R, 6S)-6-((E)-2-(4-(4-fluorophenyl)-6-isopropyl-
2-nitropyrimidin-5-yl) vinyl)-2, 2-dimethyl-1, 3-dioxan-4-yl) acetate compound of
structural formula XIX.

A solution of ((4-(4-fluorophenyl) - 6 - isopropyl - 2 - nitropyrimidin - 5 - yl) methyl)
triphenylphosphonium bromide compound of structural formula XVIII (175gm) in
dimethylsulfoxide (600m1) was added potassium carbonate (104gm), and tert-butyl 2-
((4R, 6S)-6-formyl-2, 2-dimethyl-1, 3-dioxan-4-yl) acetate (71grn) at 30°C under stirring.
The resulting reaction mixture was agitated at 70°C to 75°C for 2 hours and then reaction
mixture was cooled to 25°C and diluted with toluene (1000ml). The resulting reaction
mixture was filtered and filtrate was washed with water (1000ml), concentrated under
reduced pressure to get residue compound, which was recrystallized in methanol (500m1)

to get pure tert-butyl
nitropyrimidin-5-yl) vinyl)-2, structural formula XIX
Yield: 142gm
Purity: 99.89% (By HPLC)

2-((4R, 6S)-6-(( E)-2-(4-(4-fl uorophenyI)-6-isopropyl-2-
2-dimethyl-1, -3-dioxan-4-yl) acetate compound of

Stage 2: Preparation of tert-butyl 2-((4R, 6S)-6-((E)-2-(2-amino-4-(4-fluorophenyl)-6-

isopropylpyrimidin-5-yl) vinyl)-2, 2-dimethyl-1, 3-dioxan-4-yl) acetate compound of

structural formula XX.

The solution of tert-butyl 2-((4R, 6S)-6-((E)-2-(4-(4-fluorophenyl)-6-isopropyl-2-

nitropyrimidin-5-yl) vinyl)-2, 2-dimethyl-l, 3-dioxan-4-yl) acetate compound of

structural formula XIX (140gm) in acetone (1500ml) was added sodium dithionite

(50gm) and ammonia (25m1) at 25°C and then resulting reaction mixture was stirred of 2

hour at 40°C. The reaction mixture was diluted with toluene (450m1) and then organic

layer was separated, washed with water (2x200m1) and concentrated under reduced pressure to get residue, which was recrystallized in ethyl acetate solvent (750ml) at 0-5°C to get the title compound.
Yield: 130gm
Purity: 99.78% (By H PLC)

Stage 3: Preparation of tert-butyl 2-((4R, 6S)-6-((E)-2-(4-(4-fluorophenyl)-6-isopropyI-
2-(N-methylm ethylsulfonamido) pyrimidin-5-yl) vinyl)-2, 2-dimethyl-1, 3-dioxan-4-yl)
acetate compound of structural formula XV.

A solution of tert-butyl 2-((4R, 6S)-6-((E)-2-(2-amino-4-(4-fluorophenyl)-6-
isopropylpyrimidin-5-yl) vinyl)-2, 2-dimethyl-1, 3-dioxan-4-yl) acetate compound of
structural formula XX (100gm) in dimethoxyethane (1000m1) was added sodium tert-
pentoxide (115gm) at 25°C and then methanesulfonyl chloride (45m1) was added
dropwise at 0-5°C in 30minutes. The resulting reaction mixture was stirred for 30
minutes at 5-10°C and then dirnethyl sulfate (45m1) was added dropwise in 24 minutes at
a temperature in the range of -5°C to 0°C. The resulting reaction mixture was stirred for
one hour at 20-25°C and then it was quenched with an aqueous solution. of sodium
chloride (70gm dissolved in 700m1 water). The organic layer was separated, washed with
water (2x200mI) and stirred for 3 hours at 0-5°C to get title compound.
Yield: 119gm
Purity: 99.86% (By HPLC)

WE CLAIM:

1. A process for the preparation of rosuvastatin or pharmaceutically acceptable salts
thereof comprising the steps of
a. reacting a compound of structural formula VIII with a compound of structural
formula IX to get a compound of structural formula X,

Formula IX
R8

Formula VIII
Formula X

wherein,
R1 and R2 are alcohol protecting groups or R' and R2 taken together, form a 1, 3-diol
protecting group, R8 is -CN, -CONH2, -CON(R9R1°), -COOR9 or a group that is capable
of conversion into -COOH [R9and R10 is independently selected from hydrogen, alkyl,
aryl, arylalkyl or R9and R10 taken together with the linking nitrogen atom form a mono or
bicyclic heterocyclic which may optionally contain in all ring moieties further nitrogen,
oxygen or sulphur heteroatom and which may optionally be substituted), X is a nitro
functional group, , Y is halogen, -P(O)(C6H5)2, -S(O)2R4,
O O
or P(R5)3A O
R4 is

R5

wherein,
R' is alkyl, aryl, arylalkyl or cycloalkyl
R6 is H, alkyl, aryl, arylalkyl, CF3, halo or NO2
R7 is H, alkyl, alkyloxy, haloalkyl, monohaloalkyloxy, dihaloalkyloxy and Z is 0, N-H, N-alkyl or S.
A is halide such as chioro or bromo

b. converting a compound of structural formula X into a compound of structural
formula XI,

R8

Formula X

R8

H2N

Formula XI

c. converting a compound of structural formula XI into a compound of structural

formula X11 and

R8

H2N

Formula XI
Formula XII

d. converting a compound of structural formula XII into rosuvastatin or
pharmaceutically acceptable salts thereof.

1 9

2. The process according to claim no. I wherein reaction of a compound of structural formula VIII with a compound of structural formula IX is carried out in the presence of inorganic base in an aprotic solvent at a temperature in the range of 30°C to 80°C for a period of 30 minutes to 5 hours.

3. The process according to claim no. 2 wherein an inorganic base is selected form the group comprising of sodium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide, sodium bicarbonate, potassium bicarbonate, lithium hydroxide or lithium carbonate.
4. The process according to claim no. 2 wherein aprotic solvents is selected form the group comprising of dimethylsulfoxide, dimethylformamide, dimethylacetamide or mixture(s) thereof.

5. The process according to claim no. 1 wherein conversion of a compound of structural
formula X into a compound of structural formula XI is carried out by reacting compound
of structural formula X with sodium dithionite in the presence of ammonia at a
temperature in the range of 25°C to 40°C for a period of 30 minutes to 3 hours in ketone
solvent selected from the group comprising of acetone, methyl isobutyl ketone, 2-
butanone, 3-pentanone or mixture(s) thereof.

6. The process according to claim no. I wherein conversion of a compound of structural formula XI into a compound of structural formula XII is carried out by reacting compound of structural formula Xl with methane sulfonyl chloride in the presence of sodium tertiary pentoxide in ether solvent at a temperature in the range of -15°C to 35°C for a period of 20 minutes to 2 hours followed by the reaction with a methylating agent selected from the group comprising of methyl iodide or dimethyl sulfate.

7. A novel intenmediate compounds of structural formula VIII and X.

R$

Formula Vlll Formula X

wherein, R' and R2 are alcohol protecting groups or RI and R2 taken together, form a 1, 3-
diol protecting group, R8 is -CN, -CONH2, -CON(R9R10), -COOR9 or a group that is capable of conversion into -COOH [R9and R'U is independently selected from hydrogen, alkyl, aryl, arylalkyl or R9and R10 taken together with the linking nitrogen atom form a mono or bicyclic heterocyclic which may optionally contain in all ring moieties further nitrogen, oxygen or sulphur heteroatom and which may optionally be substituted], X is a nitro functional group, , Y is halogen, -P(O)(C6H5)2, -S(O)2R4,
O
or 1'(RS)3A
R4 is

R5

wherein,
R5 is alkyl, aryl, arylalkyl or cycloalkyl
R6 is H, alkyl, aryl, arylalkyl, CF3, halo or NO2
R7 is H, alkyl, alkyloxy, haloalkyl, monohaloalkyloxy, dihaloalkyloxy and
Z is 0, N-H, N-alkyl or S.
A is halide such as chloro or bromo

21

S. A compound of structural formula XVIII

02N

Formula XVIII
9. A compound of structural formula XIX

02N
CH3
Formula XIX

10. A use of compound of structural formula XVIII and XIX for the preparation of rosuvastatin or pharmaceutical acceptable salts thereof.