We Claims:
1. An improved process for the preparation' of Rizatriptan intermediate 4-((lH-l,2,4-triazol-
1 yl)methyl)benzenamine compound of Formula-I
which comprises reducing compound of Foirniiia-II
...... N-.N'^ff^
" V KA
N N02
Formula-II in the presence of reducing agent in water as a solvent, wherein the reducing agent is selected from Iron powder/Lewis acid, Sodium ditliionite.
2. An improved process for the'preparation of compound of Formula I
N NH2
Formula-1 which comprises reducing compound of Formula-II
i in the presence of Iron powdei/Lewis acid.
3. An improved process for the preparation of compound of Formula I
which comprises reducing compound of Formula-II

Formula-II in the presence of Iron powder/Lewis acid in water as a solvent.
4. An improved process according to any of the proceeding claims, wherein Lewis acid is selected from Calcium chloride (CaCl2), Calcium chloride dihydrate (CaCl2-2H20), Ferric chloride (FeCb), Aluminium chloride (AICI3), Aluminium bromide (AlBr3), Boron trifluroide (BF3), Boron trichloride (BC13), Tin(IV) chloride (SnCL,), Magnesium chloride (MgCl2).
5. An improved process for the preparation of compound of Formula I
Formula-I which comprises, reducing compound of Formula-II
N v N02
Formula-II in the presence of Sodium dithionate in water as a solvent.
FIELD OF THE INVENTION
The present invention relates to the green approach for the preparation of Triptan
intermediate.
The present invention particularly relates to green approach for the preparation of Rizatriptan intermediate which is highly cost effective, commercially feasible & industrially advantageous.
BACKGROUND OF THE INVENTION
Rizatriptan Benzoate is a 5-HT1 receptor agonist, which is sold under the brand name Maxalt, the chemical name for Rizatriptan Benzoate is N,N-dimethyl-5-(lH-l,2,4-triazoI-l-ylmethyl)-lHindole-3-ethanamine monobenzoate. The structural formula is:
Its empirical formula is CisH^Ns^CyHeOa, representing a molecular weight of the free base of 269.4. Rizatriptan benzoate is a white to off-white, crystalline solid that is soluble in water at about 42 mg per mL (expressed as free base) at 25°C.
U.S. Pat. No. 5,298,520 and J. S. Leslie et al., J. Med. Chem., 1995, 38, and 1799 discloses Rizatriptan, methods for its preparation and pharmaceutical formulations using the same. 4-((lH-l,2)4-triazol-l-yl)methyl)benzenamine is the key intermediate of Rizatriptan benzoate. US '520 discloses the preparation of Rizatriptan using 4-((lH-l,2,4-triazol-l-yl)methyl)benzenamine intermediate. The process disclosed in the said patent is given below:

The above process involves the use of palladium catalyst for the reduction of nitro group, catalytic hydrogenation using metal catalyst such as palladium, platinum, Raney nickel etc., requires pressurization equipment, high costs, the reaction time is long and it is necessary to control residual amount of heavy metals in the final Pharma. Hence, the above process may not be feasible at industrial level.
WO 2006/137083 Al discloses the preparation of 4-((lH-l,2,4-triazol-l-yl)methyl)benzenamine which involves the reduction of nitro compound using Raney nickel catalyst. The process is shown in the scheme given below:
Catalytic hydrogenation using metal catalyst such as palladium, platinum, Raney nickel etc., requires pressurization equipment, high costs, the reaction time is long and it is necessary to control residual amount of heavy metals in the final Pharma. Hence, the above process may not be feasible at industrial level.
The present inventors have developed completely green approach for the preparation of 4-((lH-l,2,4-triazol-l-yl)methyl)benzenamine herein referred as compound of Formula-I which involves the use of water as a solvent, which results in greater efficiency than the prior art processes with higher product purity.
OBJECT OF THE INVENTION
The main object of the invention is to provide a simple, cost effective, improved and robust process for the preparation of Rizatriptan intermediate 4-((lH-l,2,4-triazol-l-yl)methyl)benzenamine compound of Formula-I yielding at a high yield with high purity without formation of undesired impurities.

Formula-1
SUMMARY OF THE INVENTION
Accordingly, the present invention provides an improved process for the preparation - of Rizatriptan intermediate 4-((lH-l,2,4-tria2ol-l-yl)methyl)benzenamine compound of Formiila-I
tfXX
N v NH2
Formula-I which comprises reducing compound of Formula-II
N ^ N02
Formula-II in the presence of reducing agent in water as a solvent, wherein the reducing agent is selected from Iron powder/Lewis acid, Sodium dithionite.
In a preferred aspect, the present invention provides an improved process for the
! preparation of compound of Formula I
| Formula-I
j which comprises reducing compound of Formula-II
N ^ N02
J Formula-II
■
J in the presence of Iron powder/Lewis acid.
>
: In another preferred aspect, the present invention provides an improved process for
the preparation of compound of Formula I

which comprises reducing compound of Formula-II
rfXX
N v N02
Formula-II in the presence of Iron powder/Lewis acid in water as a solvent.
In yet another preferred aspect, the present invention provides an improved process for the preparation of compound of Formula I
era
N NH2
Formula-1 which comprises, reducing compound of Formula-II
N N02
Formula-II in the presence of Sodium dithionate in water as a solvent,
DETAILED DESCRIPTION OF THE INVENTION
Accordingly, the present invention provides an improved and green approach for the preparation of Rizatriptan intermediate 4-((l H-1,2,4-triazol-1 -yl)methyl)benzenamine compound of Formula-I
Formula-1 The inventors of the present invention have developed a green chemistry approach for the preparation of Formula-I a key intermediate in the preparation of Rizatriptan which involves the reduction of compound of Formula-II

The reducing agent is selected from Iron powder/Lewis acid, sodium dithionite.
By adopting the above route the inventors of the present invention have successfully developed the compound of Formula-I with good yield and high purity, the cost of the reducing agents as used in the present invention such as Iron powder as well as Lewis acids are very low and commercially viable comparatively with palladium and Raney nickel as used in the prior art.
The "Lewis acid" used is selected from Calcium chloride (CaCl2), Calcium chloride dihydrate (CaCl2-2H20), Ferric chloride (FeCl3), Aluminium chloride (A1CI3), Aluminium bromide (AlBr3), Boron trifluroide (BF3), Boron trichloride (BC13), Tin(IV) chloride (SnCL,), Magnesium chloride (MgCl2).
According to the present invention the water which is used as a solvent in the reduction of compound of Formula-II may also be used as a hydrogen source.
The present invention may also involve the use of solvent other than water when the reduction is performed in the presence of Iron powder and Lewis acid.
The inventors of the present inventions have successfully developed the reduction of compound of Formula II using sodium dithionite in Water as a solvent, wherein the current process does not require any further purification of amine intermediate of compound of Formula-I.
The present invention provides an improved process for the preparation of compound of Formula I
which comprises reducing compound of Formula-II

in the presence of Iron powder and Calcium chloride in a solvent.
In a preferred embodiment, the present invention provides an improved process for the preparation of compound of Formula I
era
N NH2
Formula-I Which comprises reducing compound of Formula-II
ZfCX
N N02
Formula-II in the presence of Iron powder and Calcium chloride in Water as a solvent.
In another preferred embodiment, the present invention provides an improved process for the preparation of compound of Formula I
N NH2
Formula-I which comprises reducing compound of Formula-II
KTCX
N v N02
Formula-II in the presence of Iron powder and FeCb in a solvent selected from Water, alcohols or their mixtures
In yet another preferred embodiment, the. present invention provides an improved process for the preparation of compound of Formula I
N NH2
Formula-I
which comprises reducing compound of Formula-II

in the presence of Sodium dithionate in water as a solvent,
In another preferred embodiment, the solvent used in the present invention is selected from water, alcohol solvents such as methanol, ethanol, n-propanol, isopropanol, n-butanol and t-butanol, hydrocarbon solvents such as benzene, toluene, xylene, heptane, hexane and cyclohexane, ketone solvents such as acetone, ethyl methyl ketone, diethyl ketone, methyl tert-butyl ketone, isopropyl ketone, esters solvents such as methyl acetate, ethyl acetate, propyl acetate, isopropyl acetate, n-butyl acetate, isobutyl acetate, sec-butyl acetate, nitrile solvents such as acetonitrile, propionitrile, butyronitrile and isobutyronitrile, ether solvents such as di-tert-butylether, dimethylether, diethylether, diisopropyl ether, 1,4-dioxane, methyltert-butylether, ethyl tert-butyl ether, tetrahydrofuran, 2-methyl tetrahydrofuran, 2-methoxyethanol and dimethoxyethane, Amide solvents such as formamide, DMF, DMAC, N-methyl-2-pyrrolidone, N-methylformamide, 2-pyrrolidone, l-ethenyl-2-pyrrolidone and/or mixtures thereof.
The compound of Formula-! as prepared according to the present invention is further converted to Rizatriptan as per the process enabled in U.S. Pat. No. 5,298,520.
While the present invention has been described in terms of its specific embodiments, certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the present invention. The invention is illustrated below with reference to inventive and comparative examples and should not be construed to limit the scope of the invention.
Examples: Example-!:
100 gm of l-(4-nitrobenzyl)-lH-l,2,4-triazole, 2000 mL of water was taken in a 3000mL round bottom flask with gentle stirring at room temperature and then added 160.0gm of Iron powder followed by 120.0 gm CaCl2 to the above reaction mass under stirring. The _,_-...u£hnlft.-.r.eantinrumixture, .was..heated-to_90.-.lD0^CLand-maintained-for_U3^Jirs.-Once_-TLC—__

complies then the reaction mass was cooled to room temperature and filter through hyflo bed. The filtered mother liquor was extracted with Ethyl acetate (3X 200mL). The combined organic layers were dried over anhydrous sodium sulfate (lOgm) and removed the solvent under reduced pressure and the obtained residue was isolated in Diisopropyl ether to yield 70.0 gm of the title compound with 82%.
Example-2:
In dry and clean 500 mL round bottom flask, lO.Ogm of 1 -(4-nitrobenzyl)-lH-1,2,4-triazole, 16.0gm of Iron powder and 12.0 gm CaCfe was taken in 200mL of Ethanol and Water mixture (9:1 ratio) with gentle stirring and the reaction mass was maintained at 55-65 C for 2-3 Hrs. Once TLC is confirmed then the reaction mixture was cooled to room temperature and filtered over hyflo bed. Absolute ethanol was recovered from filtered ML's by distillation under reduced pressure and then the residue was diluted with lOOmL of Water, which pH was adjusted to 9 to 10 with 50% aqueous sodium hydroxide solution. The basified mother liquor was extracted with Ethyl acetate (3X 50 mL). The combined organic layers were dried over anhydrous sodium sulfate (lOgm) and removed the solvent under reduced pressure and the obtained residue was isolated in Diisopropyl ether to yield 7.0 gm of the title compound with 82%.
Example-3:
10. gm of l-(4-nitrobenzyl)-lH-l,2,4-triazole was taken in to round bottom flask, 200 ml water was added, with continuous stirring 0.50gm NaOH was added to the above reaction mass. The resulting mixture was stirred at 0-5 C for 20 minutes and then added 36.0 gm of Na2S2C>4 lot wise and maintained for 2-3 Hrs. TLC complies then the reaction mixture warmed to room temperature, extracted with added Methylene chloride (3 X 50mL). The combined organic layers were dried over anhydrous sodium sulfate (lOgm) and removed the solvent under reduced pressure and the obtained residue was isolated in Diisopropyl ether to yield 2.0 gm of the title compound with 23%.
Examplc-4:
In a clean and dry round bottom flask, 20 gm of l-(4-nitro benzyl)-1H-1, 2, 4-triazole,
100.0ml of water, 20gm of Ferric (III) chloride and 22 gm Iron powder was taken at room
temperature, stirred for 20 minutes and then heated to 75-85 C, maintained for 4-6 Hrs. after
Tomprenon-oT~me"reattioirovernTCrthe"re^

filtered. The filtered ML's pH was adjusted to 7.5 to 8.5 by using 50%lye solution, extracted with added Methylene chloride (3 X 50mL). The combined organic layers were dried over anhydrous sodium sulfate (lOgm) and removed the solvent under reduced pressure and the obtained residue was isolated in Diisopropyl ether to yield 3.5 gm after isolation in Water.
i