FIELD OF THE INVENTION:
The present invention relates to a process for the preparation of (1 -methyl- 1H-1,2,4-triazol-3-yl) methanol (Formula 1) from (E. Z)-N'-(l-amino-2-ch!oroethylidene)-N-meihyllbrmohydrazide ( formula 2)
3-(ch!oromethyl)-1 -methyl- lH-l,2,4-triazole( formula 3) is one of the key starting material of Ensitrelvir(S-2l7622).
Various processes are reported in literature for the preparation of (I-methyl-1H-1,2,4-triazol-3-yl) methanol.
Chem. Pharma Bulletin. 42(1), 85, 1994, discloses a process for preparing (1-methyl-1H-1,2,4-triazol-3-yl) methanol, reacting IH-[l.2,4]triazole-3-methanol chlorination with terbutyl chlorosilicane. followed by methylation with iodo methane in sodium hydride. This process is complex and involves high cost.
CN 107879992 assigned to Shanghai Tbbmed Co Ltd, discloses a process, where 2-tritylepoxideacetamide is treated with 2-hydorxyacetamide in presence of triphenylchlormethane in solvent media and anhydrous conditions. Another process is also disclosed, where in 2-tritylepoxideacetamide is reacted with ethylformate followed by the addition of meihyl hydrazine in presence of chlorinated hydrocarbon solvent and a catalyst. This process is involves high cost and is not industrially feasible.

US5985874 assigned to Merck Sharp and Dohme Ltd, discloses a process where 1-formylhydriazine is reacted with chloroacetonitrile in large excess of POCb in presence of hydrocarbon solvent. Using this process, there will be lot of complications in isolating the compound and the work up involves multi solvents including volatile solvents and costly solvents like diethyl ether. This process also involves high cost and is not industrially feasible.
The present invention provides a process for the preparation of(l-methyl-lH-l,2,4-triazol-3-yl) methanol, which is simple, industrially viable with better yields.
OBJECTIVE OF THE INVENTION:
The main object of the present invention is to providea process for the preparation of (I-methyl-1H-1.2,4-triazol-3-yl) methanol, which is simple, economical and industrially viable.
The other object of the present invention is to provide a simple process for the preparation of 3-(chloromethyl)-1 -methyl-1 H-l ,2,4-triazol hydrochloride.
SUMMARY OF THE INVENTION:
The main aspect of the present invention is to provide a novel process for the preparation of (l-methyl-IH-l.2,4-triazol-3-yl)methanol, which comprises the following steps:
1) N-(l-amino-2-chloroethylidene)-N-methylformohydrazideof formula 2 is reacted with thionyl chloride to produce 3-(chloromethyl)-l-methyl-lH-l,2,4-triazole and its pharmaceutical!)' acceptable salts of formula 3,
2) 3-(chloromethyl)-l-melhyl-l H-1.2.4-triazole of formula 3 is treated with base in presence of water to (1 -methyl-1H-1,2,4-triazol-3-yl)methanoI

The other aspect of the present invention is to provide a simple process for the preparation of (1 -methyl-1H-1 ,2,4-triazoU3-yl)methanol, which comprises reacting N-( I -amino-2-chloroethylidene)-N-methylformohydrazide of formula 2 is reacted with thionyl chloride to produce 3-(chloromethyl)-l-methyl-1 H-1.2.4-triazo!cand its pharmaceutical!)' acceptable sails of formula 3.
DETAILED DESCRIPTION OF THE INVENTION:
The present invention relates to a novel process for the preparation of (I-methyl-1H-1.2.4-triazol-3-yl)mcthanol. which comprises the following steps:
I) N-(l-amino-2-chloroethylidene)-N-methylformohydrazide of formula 2 is reacted with thionyl chloride to produce 3-(chloromethyI)-1 -methyl-lH-l,2,4-triazole and its pharmaceutical!)' acceptable salts of formula 3,
2) 3-(chloromethyl)-l-methyl-IH-l.2,4-triazole of formula 3 is treated with base in presence of water to (1 -methyl-1H-1,2,4-triazol-3-yl)methanol

The other aspect of the present invention relates to provide a simple process for the preparation of (I -methyl-1H-1,2,4-triazol-3-yl)methanol, which comprises
i) reacting N-( I -amino-2-chloroethylidene)-N-methylformohydrazide of formula 2 is
reacted with thionyl chloride to produce 3-(chloromethyl)-l-methyl-lH-l,2,4-triazole and its pharmaceutically acceptable salts of formula 3,
ii) removing the water.
iii) dissolving the crude 3-(chloromethyl)-l-methyl-lH-],2,4-triazole in alcohol,
iv) removal of alcohol, by distillation.
According to the fust embodiment of the present invention, the base is selected from alkali metal hydroxides, alkali metal carbonates, alkali metal oxides.
According to the second embodiment of the present invention, alkali metal hydroxide is selected from the group of Sodium hydroxide, Potassium hydroxide, Magnesium hydroxide, aluminium hydroxide.
According to the third embodiment of the present invention, alkali metal carbonates is selected from the group of Sodium carbonate, Sodium bicarbonate, Potassium carbonate, Potassium bicarbonate, Magnesium Carbonate.
According to other embodiment of the present invention the alcohol used is selected from the group of Methanol, eihanol. Isopropanol. buianol or mixture thereof, preferably Methanol

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 present invention can be illustrated in one of its embodiment by the following non- limiting examples.
EXAMPLES:
Preparation of 3-(chluromcthyl)-l-mcthyl-l H-l,2,4-tria/ole hydrochloride (Compound
No:3):
100 g of (IE, Z)-N'-(l-amino-2-chloroethylidene)-N-methylformohydrazide (formula 2) added to ihionyl chloride. Then the reaction mixture was slowly heated and maintained for cyclization. After completion of reaction, excess thionyl chloride removed completely. Then eth> I acetate was added to the residue and precipitated material filtered, and dried to obtain 3-(chloroiiKihyl)-l -melln I-1 H-l .2.4-tri;r/ole hydrochloride (compound 3) a^ an olf-whitc Nolid. Yield: 90%. HPLC purity indicates > 99%. HNMR (400 Hz. DMSO-d6): 9.28 (Bra. 1 H). 8,57 (s. ll-l).4.7!(s:2H).3.87(s;3H).
Preparation of (I-metliyl-l H-l,2,4-triaxol-3-yl) methanol (Compound No:l):
To 100 gms aqueous solution of 3-(chloromethyl)-l-melhyl-l H-l.2.4-triazole hydrochloride (compound 3) base ( sodium carbonate ) was added. The resulting mixture was healed lo

reflux and maintained for longer hours. Alier completion ofreaclion. ihe reaction mas distilled out under vacuum to gel crude material. The resulting crude material was dissolved in methanol and isolated by distillation. The crude material was liaetioned under reduced pressure to get (1-melhyl-l |-|-].2.4-lriazol-3-yl) methanol as a while colour solid. Yield: 77% . HPLC purity indicates > 99%. HNMR (400 Hz, CDCb): 8.01 (s, IH), 4.74(s: 2H): 3.87 (s, 3H).