The present invention relates to the efficient solid-phase synthesis of Umglutide represented by Formula-I,
Formula-!
Liragiutide (VICTOZA-®) is a glucagon-like peptide-1 (GLP-1) receptor agonist indicated as an adjunct to diet and exercise to improve gjycemic control in adults with type 2 diabetes meilitus.
BACKGROUND OF THE INVENTION
Lifaglutide, is a long acting analogue of the naturally occurring human glucagon like peptide-i (GLP-1(7-37)) in which lysine at position 34 has been replaced with, argmine and palmitoyl group has been attached via giutamovl spacer to lysine at position 26.
Liragiutide (VICTOZA®), developed by Novo Nordisk got initial approval in United States in 2010 as subcutaneous injection.
U.S. Patent No. 6,268,343 discloses lifaglutide and process for preparing it. Wherein recombinant technology is involved in preparing Arg:M-GLP-l(7~37)-QH followed by reaction with Na-hexadecanoyl-Glu(ONSu)-C>'Bu.
US 7,273,921 R2 and US 6,451,974 B1 discloses process for acyiadon of Arg34-GLP-1 (7~ 37VOH to obtain liraelutkie.

US 9,260,474 B2 discloses solid phase synthesis of Iiraglutide characterised in that comprises a) sequential coupling of amino acids with N-terminal protection and side chain protection based on the sequence of peptide backbone of iiraglutide, wherein Fmoc-Lys( Alloc )-OH is employed for lysine;
b) deprotection of Alloc on the side chain of lysine;
c) coupling of palmifoyl-Giit-O'Bu or sequential coupling of glutamic acid and palrnitoyi chloride to the side chain of lysine;
d) removal of protective groups and cleavage of resin, to obtain crude Iiraglutide.
WO 2014/199397 A2 discloses solid phase synthesis of Iiraglutide using sequential coupling approach and fragment approach, wherein Fmoe-Lys(dde)-OIi is employed for lysine,
WO 2016/059609 AI discloses process for acylation of AfgM-GLP-S(7-37)-OH using copper agent to obtain Iiraglutide.
The prior processes for preparing Iiraglutide have disadvantages. The methods are not suitable for large scale production of Iiraglutide due to complex techniques and high costs; in processes where Alloc is employed as lysine side chain protecting group, deprotection of Alloc requires metal catalysts such as Pd(PPhj)4 which are rather expensive. Further, catalyst is moisture sensitive, reaction has to be carried out in controlled conditions and heavy metal content in final product to be considered. Hence, the processes are not commercially viable or execution problems persist.
During solid phase synthesis, it is observed that sturdy tendency of peptides to aggregate under conditions employed. It is because of the following reasons:
a) Growing peptide sequence is susceptible to form p-sheet kind of structures, which results in collapse of the peptidyl resin and
b) Hydrophobic amino acids present which cause folded peptide chain.
in such conditions, the dispersion of reagents into the peptidyl. resin is limited, coupling and deprotection. reactions will be sluggish and incomplete, thereby generating peptide

impurities leading to difficulties in purification and resulting in low yield. Hence, there remains a need to provide efficient process for preparation of liragiutide which is high yielding, scalable, cost effective, environment friendly and commercially viable by avoiding repeated cumbersome and lengthy purification steps.
OBJECTS OF THE INVENTION
The objective of the present invention is to develop simple, robust, and commercially viable sequential process for the preparation of liragiutide of the Formula 1 with the aid of inorganic salts, novel and efficient coupling conditions,
BRIEF DESCRIPTION OF DRAWINGS
Figure 1: Flow chart for process for solid-phase synthesis of liragiutide (Formula-1) according to the present invention.
Figure 2; Illustrates HPLC chromatogram of Liragiutide
SUMMARY OF THE INVENTION
An embodiment of the present invention involves synthetic process for the preparation of liragiutide comprising the following steps:
a) Loading of C-tenninai glycine to a resin solid-phase support in the presence of coupling agent.
b) Sequential, coupling of Na- and side chain protected amino acids to prepare backbone of liragiutide. in the presence of coupling agent and an inorganic salt.
c) Deprotection of side chain protecting group of lysine.
d) Coupling of y-glutarme acid and palmitic acid in sequential manner to the side chain of lysine in the presence of coupling agent and an inorganic salt.
e) Crude liragiutide is obtained by removal of protective groups and cleavage of peptide from the resin.
f) Purification of crude 1 imglutide,
The. schematic description of the process is as shown in Figure - !

The approach employed is solid phase peptide synthesis of liraglutide fay sequential approach and involves inorganic salts during coupling along with regular coupling agents and additives. The method offers completion of coupling and deprotection reactions and reduction in raeemizatlori and thereby control the isomeric impurities which, are very close to the target molecule and in turn ease the purification process of the peptide. For further improving the present invention, in said step-A). wang resin is employed as resin solid-phase support and coupled to Fmoe-Giy-QH using DIC as coupling agent and MDC as solvent.
The use of 2-chlorotrityi resin. fC'TC) as solid-phase support was limited because couplings were sluggish and not going, for completion after 15 amino acids sequence and the peptide attached to C'TC resin being labile and prone to be leached out in mild acidic conditions employed during coupling/washing cycles. Since, synthesis of liraglutide involves multistep, at each stage partial leaching occurs leading to reduction in overall yield,
For further improving of the present invention, In said siep-B), comprises following steps:
BI) deprotection of Fmoc protecting group from Fmoc-Giy-resin using Piperidine / DMF
or Piperidine, DBU, DMF mixture to get H-G ly-resin.
B2) washing the loaded resin
B3) coupling of Fmoc-Arg(.Pbf)-OH to H-G ly-resin in the presence of coupling agent,
coupling additive, inorganic salt and base.
B4) by repeating steps Bi, B2 and B3, liraglutide backbone is synthesized, wherein in
step-.B3 protected amino acids are sequentially coupled to get liraglutide backbone.
For Further improving the present invention, in said step-B) and D) coupling agent was
selected from the group consisting of HBTLJ, COMU, DEPBT or DIC,
Coupling additive was selected from the group consisting of oxyma pure or HOBt. base
was selected from DIPEA, NMIV5 or TMP and inorganic salt selected from die group
consisting of magnesium chloride, zinc chloride or copper chloride.
As said in step-B2) loaded resin was washed with 0.01 - 0.1 M HOBt in DMF or
Isopropanol

For further improving the present invention, as said in step-B), Mtt used as protective group for lysine and as said in step-C), the protective group Mtt from the side chain of lysine removed by using TPA/MDC or HFIP/TES/TFE/MDC.
For Further improving the present invention, in said step-D), palmitoyl-glutamie acid (Pal-Glu) side chain coupled in the presence of coupling agent selected from the group consisting of HBTU, COMli, DEP.BT or DIC; coupling additive selected from the group consisting of oxyma pure or FIOBt; base selected from D1PEA, NMM or IMP and inorganic salt selected from the group consisting of magnesium chloride, zinc chloride or copper chloride.
Another embodiment of the present invention involves synthetic process for the preparation of liragkrtkle comprising the following, steps;
a) Coupling of Na-Fmoc-protected glycine (Fmoc-Giy-OH) to a resin solid-phase support in the presence of coupling agent,
b) Sequential coupling of Ma- and side chain protected amino acids to prepare backbone of liragkitide, in the presence of coupling agent and an inorganic salt.
c) Depfotection of side chain protecting group of lysine.
d) Coupling of painiitoyl-gluiamic acid (Pal-Glu) side chain to the side chain of lysine in the presence of coupling agent and an inorganic salt.
e) Crude liragkitide is obtained by removal of protective groups and cleavage of peptide from the resin.
f) Purification of"crude liragkitide.
For Further improving the present invention, in said step-D), palmitoyl-glutamie- acid (Pal-Glu) side chain coupled in the presence of coupling agent selected from the group consisting of HBTU, COMIJ, DEPBT or DIC; coupling additive selected from the group consisting of oxyma pure or HOBt; base selected from DIPEA, NMM or TMP and inorganic salt selected from the group consisting of magnesium chloride, zinc chloride or copper chloride.
Yet another embodiment of the present invention involves synthetic process for the preparation of liragkitide comprising the following steps:

i) Coupling of Na-Frnoc-proteeled glycine (Fmoc-Gly-OH) to a resin solid-
phase support in the presence of coupling agent,
ii) Sequential coupling of Na- and side chairs protected amino acids to prepare backbone of iiraglutide, in the presence of coupling agent and an inorganic salt.
Hi.) Fmoc-deproiection of the loaded amino acid using pipeddine in DMF or Fiperidine/ DBUY DMF mixture,
iv) After each Fmoc deprotection step washing step using HOBt in DMF.
v) Deprotection of side chain protecting group of lysine
vi) Coupling of palmitoyl-gkttamic acid (Pal-Glu) side chain to the side chain of lysine in the presence of coupling agent and an inorganic salt.
vii) Crude iiraglutide is obtained by removal of protective groups and cleavage of peptide from the resin. Purification of crude iiraglutide. Further as an improvements to. the above embodiments, amino acids numbered 9 to 13 [i.e Fmoc~GIu(OtBu)9, Pmoe-Giy!0, Fmoc-ThrftBu)'1, F.moc-Phe!2, Fmoc-Tlir{tBiOi3l are coupled at an elevated temperature of around 30 — 45 °C to form liragiutide backbone.
DETAILED .DESCRIPTION OF THE INVENTION
The present invention relates to an efficient process for the preparation of Iiraglutide by-sequential coupling employing solid phase approach. It involves sequential coupling of protected amino acids to prepare backbone of Iiraglutide arid upon completion of linear sequence, synthesis was extended from lysine side chain by adding y-glutamie acid and palmitic acid, followed by removal of protective groups, cleavage of the peptide from solid support and purification of crude Iiraglutide obtained. The present invention also involves the usage of inorganic salts during the coupling, wash with HOBt in DMF solution after Fmoc-deprotection step to suppress the aggregation of peptides and ensure reactions are going for completion, and thus avoid deletion sequences and improve the process yield.
ABBREVIATIONS:
ACN: Acetonitrile

Boc: rert-Butyloxycaxbony]
COMU: l-Cyanb-2-ethoxy-2--oxoe{h>1ideriani[inooxy)dimethylamino-morpho!i,no-
carbenium hexafiuorophosphate
CuCb: Copper chloride
DBU: j,8-Diazabicyclo[5.4.0jundec-7-ene
DEPBT: 3-(Diethoxyphosphoryloxy)-l.J2,3-benzotriazin-4(3.//}-ofie
DIC: iV.A''-diisopropyicarbodiiniide
DMAP; Dimethylami.no pyridine
DMF: A'.A'-DimethylfoiTOarnide
DIPEA: DHsopropylethylamine
Fmoc: 9-fluorenylmethoxyearbonyI
HB'T'U; 0-Benzotriazole-N,N,N',N'-tetram.ethyi uranium. he.xafluorophosph.ate
HGBt: A'-Hydroxybenzotriazole
HFIP: l,l,l,3,3,3-Hexafluro-2-propanol
Mtt: Methyl trityl
MeOH: Methanol
MgCij: Magnesium Chloride
NMM: A'-methyimorpholme
NMP: N-Methyl-2-pyrrolidone
TES: Trifithyisilane
TFE: Trifiuroethano!
TFA: Trifhioroacetic acid
Pbf: 2,2.4,6,7-Pentamethyldibydvobenzofurane
Pd(PPh.3}4: Tetrakis(trtphenylphosphme)pa!ladtuni(0)

RT: Room temperature
•'Bu: tert-Butyi
TiS: Triisopropyl SUane
Trt: Trityl
IMP: 2,4,6-Trimethyipyridine
Z11CI2: Zinc chloride
The invention is represented by following examples. These examples are for illustration only and hence should not be construed as limitation of the scope of invention,
Example 1: Synthesis of Livaglutide using MgGb
Stage-1; Synthesis of ■Frnoc-Giy37~Wang Resin
The Wang resin (0.3 -0.6 mmol/g, loading capacity) was loaded to peptide synthesis vessel, washed twice with 10 v of MDC, decanted the washings, added 10 v of MDC and kept for swelling for 1 h. Fmoc-Gly-OH (3,0 - 5.0 eq.) was dissolved in MDC, added minimum quantity of DMF to obtain clear solution and the mixture was transferred to reaction vessel. Added DIPC (3.0 - 6.0 eq.) followed by DMAP (0.0S.¬O.I eq.) to the reaction vessel and stirred for 1.0 - 3.0 h, at rt. Drained the reaction mass and washed the amino acid loaded resin twice with MDC followed by DMF. Capping of the imreaeted functional sites were carried out using acetic anhydride and DIPEA.
Stage-2: Synthesis of .Fmoe-Arg(Pbf)36-Gly3'?-Wang Resin
Fmoc-deprotection of the loaded amino acid was earned out by washing the resin using 15-25 % piperidine in DMF two times for 5 and 10 min. followed by the resin was washed with 3-5*8 v 0.01 - 0.1 M HQBi: in DMF. The Fmoc-Arg(Pbf}-OH (2.0 - 4.0 eq.), was coupled using coupling agents such as HBTLf COMU, DEPBT, and DIG, preferably DEPBT (2.0 - 4,0 eq.) and oxymapure, HOBt, preferably oxymapure (2.0 - 4.0 eq.) and DIPEA, NMM, TMP, preferably DiPEA (5.0 -8.0 eq.) and MgCb, ZnCh, preferably MgClj (0.0 i - 0.1 eq) and DMF/NMP mixture as solvent. The reaction was

performed in nitrogen atmosphere arid r,t. Upon completion of coupling of the amino acid confirmed by Kaiser Test, the excess reagents were drained and washed the peptidyl resin with 3 x 10 v DMF.
Stage-3: Synthesis of Fmoc-Gly35-Arg(Pb.f)3f,-GIy37-Waiig Resin
Fmoc-deprotection of the loaded amino acid was carried out by washing the resin using 15-25 % piperidine in DMF two times for 5 and 10 min. followed by the resin was washed with 3-5*8 v 0.01 - 0.1 M HOBt in DMF. The Fmoc-Gly-OH (2,0 - 4.0 eq.), was coupled using coupling agents such as HBTU, COMU, DEPBT, and DIC, preferably DEPBT ("2.0 - 4.0 eq.) and oxymapure, HOBt, preferably oxyrnapure (2.0 - 4.0 eq.) and DIPEA, NMM, IMP, preferably DIPEA (5.0 -8.0 eq.) and MgCb, ZnCb, preferably MgCb (0.0.1 - 0.1 eq) and DMF/NMP mixture as solvent. The reaction was performed in nitrogen atmosphere and r.t. Upon completion of coupling of the amino acid confirmed by Kaiser Test, the excess reagents were drained and washed the peptidyl resin with 3 x 10 v DMF.
Stage-4: Synthesis of Fmoc~Arg(Pbi)34-GH^s-Arg(Pbi)3*-G-ly37-Wang Resin
Fmoc-deprotection of the loaded amino acid was carried out by washing the resin using 15-25 % piperidine in DMF two times for 5 and 10 min. followed by the resin was washed with 3-5*8 v 0.01 - 0.1 M HOBt in DMF. The Fmoc-Arg(Pbf)-OH (2.0 - 4.0 eq.), was coupled using coupling agents such as HBTU, COMU, DEPBT, and DIC, preferably DEPBT (2,0 - 4.0 eq.) and axyniapare, HOBt, preferably oxymapure (2.0 - 4.0 eq.) and DIPEA, NMM, TMP, preferably DIPEA (5.0 -8.0 eq.) and MgCb, ZnCb, preferably MgCb (0,01 - 0.1 eq) and DMF/NMP mixture as solvent. The reaction, was performed in nitrogen atmosphere and r.t. Upon completion of coupling of the amino acid confirmed by Kaiser Test, the excess reagents were drained and washed the peptidyl resin with 3 x 10 v DMF.
Stage-5: Synthesis of Fmoc-VaP3~Arg{Pbf)34-Gly35-Arg(Pbf)36-Giy37-VVang Resin
v) Fmoc-deprotection of the loaded amino acid was carried out by washing the resin using 15-25 % piperidine in DMF two times for 5 and 10 min. followed by the resin was washed with 3-5*8 v 0.01 - 0.1 M HOBt in DMF. The Fmoc-Val-OH (2.0 - 4.0 eq.), was coupled using coupling agents such as HBTU, COMU, DEPBT, and DIC, preferably

DEPBT (2.0 - 4.0 eq.) and oxyroapure, HOBt, preferably oxyniapure (2.0 - 4.0 eq.) and DIPEA, NMM, IMP, preferably DIPEA (5.0 - 8.0 eq.) and MgCb, ZnCb, preferably MgCb (0.0i - 0.1 eq) and DMF/NMP mixture as solvent The reaction was performed in nitrogen atmosphere and r.t. Upon completion of coupling of the amino acid confirmed by Kaiser Test, the excess reagents were drained and washed the peptidyi resin with 3 x 10 v DMF.
Stage-6: Synthesis of Fiiioc-Ley32~\raI33-Arg(Pbt)M-GIyJS~Arg(Pbl)3*-G!y37-Wang Resin
Pmoc-deproteetion of the loaded amino acid was carried out by washing the resin using 15-25 % piperidme in DMF two times for 5 and 10 msn. followed by the resin was washed with 3-5*8 v 0.01 - 0.1 M HOBt in DMF. The Fmoc-Leu-OH (2.0 ~ 4.0 eq.), was coupled using coupling agents such as HBTU, COMU, DEPBT, and DiC, preferably DEPBT (2.0 - 4.0 eq.) and pxymapure, HOBt, preferably oxymapwe (2.0 - 4.0 eq.) and DIPEA, NMM, TMP, preferably DIPEA (5.0 -8.0 eq.) and MgCb, ZnCb, preferably MgCb (0.01 - 0.1 eq) and DMF/NMP mixture as solvent. The reaction was performed in nitrogen atmosphere and r.t. Upon completion of coupling of the amino acid confirmed by Kaiser Test, the excess reagents were drained and washed the peptidyi resin with 3 x 10 v DMF.
Stage-7; Synthesis of Fnsoc-Trp(Boe)3'-Leu^-VaF-ArgCPbQ^-GIy^-ArgCPbf)36-Gly37-Wan.g Resia
Fmoc-deprotection of the loaded amino acid was carried out by washing the resin using 15-25 % piperidine in DMF two times for 5 and 10 min. followed by the resin was washed with 3-5*8 v 0.0 L - 0.1 M HOBt in DMF. The Fmoc-Trp(Boc)-OH (2.0 - 4.0 eq,), was coupled using coupling agents such as HBTU, COMU. DEPBT, and DIC, preferably DEPBT (2.0 - 4.0 eq.) and oxyniapure, HOBt, preferably oxyniapure (2.0-4.0 eq.) and DIPEA, NMM, TMP, preferably DIPEA (5,0 -8,0 eq.) and MgCb, ZnCb, preferably MgCb (0.01. - 0.1 eq) and DMF/NMP mixture as solvent. The reaction was performed in nitrogen atmosphere and r.t. Upon completion of coupling of the amino acid confirmed, by Kaiser Test, the excess reagents were drained and washed the peptidyi resin with 3 x 10 v DMF.

Stagc-8: Synthesis of Fmoc-Ala3ft-Trp(Boc)31-Leu32-Va !33~Arg(Pbi)w~GlyJS-Arg(Pbi)3M31y37~WaHg Resin
Fmoc-deprotection of the loaded amino acid was carried out by washing the resin using 15-2.5 % piperidine in DMF two times for 5 and 10 rain, followed by the resin was washed with 3-5*8 v 0.01 - 0.1 M HOBt in DMF. The Fmoc-Ala-OH (2.0 - 4,0 eq.), was coupled using coupling agents su'eh as HBTU, COMU, DEPBT, and DSC, preferably DEPBT (2.0 - 4.0 eq.) and oxymapure, HOBt, preferably oxymapure (2.0 - 4,0 eq.) and DiPEA, NMM, TMP, preferably DTPEA (5.0 -8.0 eq,) and MgCla, ZnCia, preferably MgCb (0.01 - 0.1 eq.) and DMF/NMP mixture as solvent The reaction was performed in nitrogen atmosphere and r.t. Upon completion of coupling of the amino acid confirmed by Kaiser Test, the excess reagents were drained and washed the peptidyl resin with 3 x 10 v DMF.
Stage-9: Synthesis of Fi«oc-Ik29-Aia3,,-~Trp(BQc)3!-U»;,2~Va.SB~Arg(Pbi)34~Gly35-Arg(Pfof)36-Gly37-Wang Resin
Fmoodeprotection of the loaded amino acid was carried out by washing the resin, using 15-25 % piperidine in DMF two times for 5 and 10 min. followed by the resin was washed with 3-5*8 v 0.01 - 0.1 M HOBt in DMF. The Fmoc-Ik-OH (2.0 - 4.0 eq.}, was coupled using coupling agents such as T-IBTU, COMU, DEPBT, and DIG, preferably DEPBT (2.0 - 4.0 eq.) and oxymapure, HOBt„ preferably oxymapure (2.0 - 4.0 eq.) and DIPEA, NMM, TMP, preferably DiPEA (5.0 -8.0 eq.) and MgCh, ZnCh, preferably MgCb (0.01 - 0.1 eq) and DMF/NMP mixture as solvent. The reaction was performed in nitrogen atmosphere and. r.t. Upon completion of coupling of the amino acid confirmed by Kaiser Test, the excess reagents were drained and washed the peptidyl resin with 3 x 10 v DMF,
Stage-10: Synthesis of F.raoe-Phe2Miew~Ala30-Trp(Boe)3i-Leu3:-VaF-Arg(Pbf)34-Gjy3S-Arg(PbOM-Gly37-Wang Resin
Fmoe-deprotection of the loaded amino acid was carried out by washing the resin, using 15-25 % piperidine in DMF two times for 5 and 10 min. followed by the resin was washed with 3-5*8 v 0.01 - 0.1 M HOBt in DMF, The Fmao-Phe-OH (2,0 - 4.0 eq,), was coupled using coupling agents such as HBTU< COMU, DEPBT, and DSC, preferably

DEPBT (2,0 - 4.0 eq.) and oxymapure, HOBt, preferably oxyraapure (2.0 - 4.0 eq.) and DIPEA, NMM, TMP, preferably DIPEA (5.0 - 8.0 eq.) and MgCh, ZnCb, preferably MgCI? (0.01 - 0.1. eq) and DMF/NMP mixture as solvent. The reaction was performed in nitrogen atmosphere and. r.t, Upon completion of coupling of the amino acid confirmed by Kaiser Test, the excess reagents were drained and washed the peptidyi resin with 3 x 10 v DMF.
Stage-i 1: Synthesis of Fjiioc-Gtw(0,Bu)27-Phe2S~IIe39-Ala3fl-Trp(Boc)3!-Leu3:-Val33-Arg(Pb034-Giy35-Arg(Pbf)M-GSy37-WangResi!i
xi) Fmoc-deproiection of the loaded amino acid was carried out by washing the resin using 1.5-25 % piperldine in DMF two times for 5 and 10 min. followed by the resin was washed with 3-5*8 v 0.01 - 0.1 M FlOBt in DMF, The Fmoc-Glu(0'Bu)-OH (2.0 - 4.0 eq.), was coupled using coupling agents such as HBTU, COMU, DEPBT, and DIC, preferably DEPBT (2.0 - 4.0 eq.) and oxymapure, HOBt, preferably oxymapure (2.0 ~ 4.0 eq.) and DIPEA, NMM, TMP, preferably DIPEA (5.0 -8.0 eq.) and .MgCh, ZnCb, preferably MgCb (0.01 - 0. i eq) and DMF/NMP mixture as solvent The reaction was performed in nitrogen atmosphere and r.t. Upon completion of coupling of the amino acid confirmed by Kaiser Test, the excess reagents were drained and washed the peptidyi resin with 3 x 10 v DMF,
Stage-I2: Synthesis of Fmoc-Lys(Mtt)26-Glii(0*Bii)"~PheI8-I.le29-Aia:K,-Trp(Boc>}1-I^u3^ValM-Arg(Pbf)34--Gly3S-Arg(Pbf)3*--Gly37-Wang Resin
Fmoe-deprotection of the loaded amino acid was carried out by washing the resin using 15-25 % piperidine in DMF two times for 5 and 10 min. followed by the resin was washed with 3-5*8 v 0.01 - 0.1 M HOBt in DMF, The Fmoc-Lys(Mtt)-OH (2.0 - 4.0 eq.), was coupled using coupling agents such as HBTU, COMU, DEPBT, and DIG, preferably DEPBT (2.0 - 4.0 eq.) and oxymapure, HOBt, preferably oxymapure (2,0 - 4.0 eq.) and DIPEA, NMM, TMP, preferably DIPEA (5.0 -8.0 eq.) and. MgCh, ZnCb, preferably MgCh (0.01 - 0.1 eq) and DMF/NMP mixture as solvent. The reaction was performed in nitrogen atmosphere and r.t. Upon completion of coupling of the amino acid confirmed by Kaiser Test, the excess reagents were drained and washed the peptidyi resin with 3 x 10 v DMF.

Stage-13: Synthesis of .Fmoi>-AJa2S-LysCMtt)^-<;i«(O'Bu)"-PheM-lIe29-AlaJ0~ TrjKBoc^^Uu^-VaF-ArgCPbO^-^ly^-AitlCPbO^-^ly^-WaagRcsin
Fmoc-deprotection of the loaded amino acid was carried out by washing the resin, using 15-25 % piperidine in DMF two times for 5 and 10 rain, followed by the resin was washed with 3-5*8 v 0.01 - 0.1 M HOBt in DMF. 'Hie Fmoc-Aia-OH (2.0 - 4.0 eq.), was coupled using coupling agents such as HBTU, COMU, DEPBT, and DIG, preferably DEPBT (2.0 - 4.0 eq.) and oxymapure, HOBt, preferably oxymapure (2.0 - 4.0 eq.) and DIPEA, NMM, TMP, preferably DIPEA (5.0 -8.0 eq.) and MgCE, ZnCh, preferably MgCh (0.01 - 0.1 eq) and DMF/NMP mixture as solvent. The reaction was performed in nitrogen atmosphere and r.t Upon completion of coupling of the amino acid confirmed by Kaiser Test, the excess reagents were drained and washed the peptklyl resin with 3 x 10 v DMF.
Stage-14: Synthesis of .FiHoc-A:la24-A!aJ5-Lys(MK)2«-Giii(0*Bu)27-Phe2a-IIe:9-Aia30-Trp(Boc)3,-LeaJ2-^aP3~Arg(Pb034-Gly3S-Arg(Pbf)3OH (2.0 - 4.0 eq.), was coupled using coupling agents such as HBTU, COMU, DEPBT. and DIC, preferably DEPBT (2.0 - 4.0 eq.) and oxymapure, HOBt, preferably oxymapure (2.0 - 4,0 eq.) and

DIPEA, NMM, TMP, preferably DIPEA (5,0 -8,0 eq.) and MgCb, ZnCb. preferably MgCb (0.01. -0.1 eq) and DMF/NMP mixture as solvent. The reaction was performed in nitrogen atmosphere and r.t. Upon completion of coupling of the amino acid confirmed by Kaiser Test, the excess reagents were drained and washed the peptidyi resin with 3 x 10 v DMF.
Stage-I6: Synthesis of Fm0C-GIy22~Gin{Trt)2-^
Phe2MJe25-AIa3«-Trp(Boe)3!^^
Wang Resin
Fmoc-deprotection of the loaded amino acid was carried out by washing the resin using .15-25 % piperidtne in DMF two times for 5 and 10 min. followed by the resin was washed with 3-5*8 v 0.01 - 0.1 M HOB!, in DMF. The Fmoc-Giy-OH (2.0 - 4.0 eq.), was coupled using coupling agents such as HUTU, COMU. DEPBT, and DIG, preferably DEPBT (2.0 -4.0 eq.) and oxymapure, HOBt, preferably oxymapure (2.0 - 4.0 eq.) and DIPEA, NMM, TMP, preferably DIPEA (5.0 -8.0 eq.) and MgCb, ZnCb, preferably MgCb (0.01 - 0.1 eq) and DMF/NMP mixture as solvent. The reaction was performed in nitrogen atmosphere and r.t. Upon completion of coupling of the amino acid confirmed by Kaiser Test, the excess reagents were drained and washed the peptidyi resin with 3 x 10 v DMF. Stage-17: Synthesis of Fmo<>^lu(0^)2M3ly2^^lii(Trt)I^AlaM-AIaM-Lyg(Mtt)2*--
Arg(Ptjf)3fi-Gly17-Wang Resin
Fmoc-dsprotection of the loaded amino acid was carried out by washing the resin using. 15-25 % piperidtne in DMF two times for 5 and 10 min. followed by the resin was washed with 3-5*8 v 0.01 ~ 0.1 M HOBt in DMF. The Fmoc-Glu(0'Bu)-OH (2.0 - 4.0 eq.), was coupled using coupling agents such as HBTU, COMU, DEPBT, and DIG, preferably DEPBT (2.0 -4.0 eq.) and oxymapure, HOBt, preferably oxymapure (2,0 - 4.0 eq.) and DIPEA, NMM, TMP, preferably DIPEA (5.0 -S.0 eq.) and MgCb, Zr.Cb, preferably MgCb (0.01 - 0.1 eq) and DMF/NMP mixture as solvent. The reaction was performed in nitrogen atmosphere and r.t. Upon completion of coupling of the amino acid confirmed by Kaiser Test, the excess reagents were drained and washed the peptidyi resin with 3 x 10 v DMF.

Stage~18: Synthesis of Fraoc-Lc«w-GIu(OlBu)2,-Gly3M;iiiCrrtJIJ-AlaM-Ala25-Lys(Mtt)36-I3-AIa24-Ala2S-LyKMt()^6~Gta(OlBu)2M»he^8-Ue2*-AIaw-Trp(Boc)3,-
LeuiJ-Va3B-Arg(Pbi)i4-GSy35-Arg(Pbf)3(,-G!y37~.WatigMesin

Fmoe-deproteciion of the loaded amino acid was carried out by washing the resin using 15-25 % piperidine in DMF two times for 5 and 10 min. followed by the resin was washed with 3-5*8 v 0.01 - 0.1 M HOBt in DMF. The Fmoc-Sejf Bu)-OH (2.0 - 4.0 eq.}; was coupled using coupling agents such as HBTU, COMU, DEPBT, and DfC, preferably
S DEPBT (2.0 -4.0 eq.) and oxymapure, HOBt, preferably oxymapure (2,0 - 4.0 eq.) and D1PEA, "NMM, TMP, preferably D1PEA (5.0 -8.0 eq.) and MgCh, ZnCl-j, preferably MgC1.3 (0.01 -0.1 eq) and DMF/NMP mixture as solvent. The reaction was performed in nitrogen atmosphere and r.t. Upon completion of coupling of the amino acid confirmed by Kaiser Test, the excess reagents were drained and washed the peptidyl resin with 3 x
3 10 v DMF.
Shsge-21: Synthesis of Fmoc-SerCBiO^-SerCBuJ^-TyrCB^^-LeH^-GiuCO'Bu)21-
Gl^-Gto^rt^-AIaM-AU^-LysCMtt^MJluCO'Buj^-Phe^Il^-Ala30-
Trp(Boc)J1-Leu3I-V3l3J~Arg(Pbf)w-^]yJ5-Arg(Pbf)36-Gly37-Wan8Resia
Fmoc-deprotection of the loaded amino acid was carried out by washing the resin using 5 55-25 % piperidine in DMF two times for 5 and 10 min. followed by the resin was washed with 3-5*8 v 0.01 - 0.1 M HOBt in DMF. The Fffioc-Ser('Bu>GH (2.0 - 4.0 eq.), was coupled using coupling agents such as HBTU, COMU. DEPBT, and DIG, preferably DEPBT (2.0 - 4,0 eq.) and oxymapure, HOBt, preferably oxymapure (2,0 - 4.0 eq.) and DIPEA, NMM, TMP, preferably D1PEA (5.0 -8.0 eq.) and MgCh, ZnC!2, preferably 0 MgCh (Q.01 - 0.1 eq) and DMF/NMP mixture as solvent. The reaction was performed in nitrogen atmosphere and r.t. Upon completion of coupling of the amino acid confirmed by Kaiser Test, the excess reagents were drained and. washed the peptidyl resin with 3 x 10 v DMF.
Stage-22: Synthesis of F£noc-Vait«,-SerCBu)!7-Ser(tBu)ls-Tyj-(!Bii)1"-Len20-5 Glu(0%u)2i-GSy2^Gln(Tr^
AUM-Trp(Boc)3MLeu32-VaP-Arg(PbOw^lj^-Arg(PbO^~GIy37-Wang Resin
Fmoc-deprotection of the loaded amino acid, was carried out by washing the resin using
15-25 %■ piperidine in DMF two times for 5 and 10 min. followed by the resin was
washed with 3-5*8 v 0.01 - 0.1 M HOBt in DMF. The Fmoc-Vai-OH (2.0 - 4.0 eq.), was
0 coupled using coupling agents such as HBTU, COMU, DEPBT. and DIG, preferably

DEPBT (2.0 -4.0 eq.) and oxymapure, HOBt, preferably oxymapure (2.0 - 4.0 eq.) and DIPEA, NMM, IMP, preferably DIPEA (5.0 - 8.0 eq.) and MgCb. ZnCb, preferably MgCb (0.01 - 0.1 eq) and DMF/NMP mixture as solvent. The reaction was performed in nitrogen atmosphere and r.t. Upon completion of coupling of the amino acid confirmed by Kaiser Test, the excess reagents were drained and washed the peptidyl resin with 3 x JOvDMF.
Siage-23: Synthesis of Fmoe-Asp{OfB«)iM'Tdl6-Ser(,g«)1T-Ser(tBu)1^
Leu^-GhiCO'Bu^-GJy22^^
Ile2*,-A]aw~Trp(8oc)M-~Leu^
Fmac-deprotection of the loaded amino acid was carried out by washing the resin using 15-25 % piperkhne in DMF two times for 5 and 10 min. followed by the resin was washed with 3-5*8 v 0.01 - 0.1 M HOBt in DMF. The Fmoe-Asp(0'Bu)-OH (2.0 - 4.0 eq,), was coupled using coupling agents such as HBTU, COMU. DEPBT, and DIG, preferably DEPBT (2.0 -4.0 eq.) arid oxymapure, HOBt, preferably oxyrnapure (2.0 - 4.0 eq.) and DIPEA, NMM, TMP, preferably DIPEA (5.0 -8.0 eq.) and MgCb, ZnCb, preferably MgCb (0.01 - 0.1 eq) and DMF/NMP mixture as solvent. The reaction was performed in nitrogen atmosphere and r.t. Upon completion of coupling of the amino acid confirmed by Kaiser Test, the excess reagents were drained and washed the peptkiyl resin with 3 x 10 v.DMF.
Stagc-24: Synthesis of FfH0c-Ser(lBii)H~Asp(OtBu)iS-ValI"~S€r(tBa)l7-Ser(tBu),8~
Tyr(*Bu)i9-I^-u20-^lu(O*Bu)2l-^ly"
GluCO'Bu^-Phe^-He^-AlaW-T^
Arg(Pht)M--GIyJ7-WaHg ResM
Fmoc-deprotection of the loaded amino acid was carried out by washing the resin using 15-25 % piperidine in DMF two times for 5 and 10 min. followed by the resin was washed with 3-5*8 v 0.01 - 0.1 M HOBt in DMF. The fmoc-SeifBu)-OH (2.0 - 4.0 eq.), was coupled using coupling agents such as HBTU, COMU, DEPBT, and DIC, preferably DEPBT (2.0 -4.0 eq,) and oxyrnapure,. HOBt, preferably oxyrnapure (2.0 - 4.0 eq.) and DIPEA, NMM, TMP, preferably DIPEA. (5.0 -8.0 eq.) and MgCb, ZftCb. preferably MgCb. (0.01 - 0.1 eq) and DMF/NMP mixture as solvent. The. reaction was performed in

nitrogen atmosphere and r.t. Upon completion of coupling of the amino acid confirmed by Kaiser Test, the excess reagents were drained and washed the peptidyl resin with 3 x 10 v DMF.
Stage-25: Synthesis of Fmoc-TiirC'BiO^-SerC'Bu^-A^ SerC'Bu^-TyrCBuV'-Le^^lulO^
GIuCO^u^'-Ph^Mle^^Iii^-TrpCBoc^^Leu^-VaF-Ar^j^f^-^Iy35-Arg(PbOM-GIy37-Wang Resin
Fmoc-deprotection of the loaded amino acid was carried out by washing the resin using 15-25 % piperidine in. DMF two times for 5 and 10 min. followed by the resin was washed with 3-5*8 v 0.01 - 0.1 M HOBt in DMF. The Fmoc-Thr('Bu)-OH (2.0 - 4.0 eq,), was coupled using coupling agents such as HBTU', COMU, DEPBT, and DIG, preferably DEPBT (2.0 -4.0 eq.) and oxymapure, HOBt, preferably oxymapisre (2.0 - 4.0 eq.) and DIPEA, NMM, TMP, preferably DIPEA (5.0 -8.0 eq.) and MgCia, ZnCb, preferably JvlgCi? (0.01 - 0.1 eq) and DMF/NMP mixture as solvent. The reaction was performed in nitrogen atmosphere and at an elevated temperature around 30-45 ^C. Upon completion of coupling of the amino acid confirmed by Kaiser Test, the excess reagents were drained and washed the peptidyl resin, with 3 x 10 v DMF,
Stage-26: Synthesis of Fmo^Phe^-ThrOBH)13-^
SerCBu)"-^rCBu)w-Tyr(lBu)M^^
Lys(Mtt)26^I«(.OtBu)27-Phe3Mle?9-AIaM-Trp(.Boc)3,-Uu3^VaF-Arg{Pbf)3<-
G$yJ5-Arg(Pbf}36-Giy3MVa«g Resin
Fmoc-deprotection of the loaded amino acid was carried out by washing the resin using 15-25 % piperidine in DMF two times for 5 and 10 min. followed by the. resin was washed with 3-5*8 v 0.01 - 0.1 M HOBt in DMF. The Fmoc-Phe-OH (2.0 - 4.0 eq.), was coupled using coupling agents such as HBTU, COMU, DEPBT, and DIG, preferably DEPBT (2.0 -4,0 eq.) and oxymapure, HOBt, preferably oxymapure (.2.0 - 4.0 eq.) and DIPEA, NMM, TMP, preferably DIPEA (5.0 -8.0 eq.) and MgC!;, ZnCh, preferably MgCE (0.01 - 0.1 eq) and DMF/NMP mixture as .solvent. The reaction was performed in nitrogen, atmosphere and at an elevated temperature around 30-45 °C. Upon completion of

coupling of the amino acid confirmed by Kaiser Test, the excess reagents were drained and washed the peptidyl resin with 3x10 v DMF.
Stage-27: Sya thesis of Frnoc-Thif Bu)11-Phe12-Thr('B«)13-SerCBu)l-,-Asp{0'B«)IS-
Val^-SerCBuy^SerCBiO^-TyK'Bu)^^
Arg(Pbf}34-GIy33-.4rg(Pbfj3fi-Gly37-Wang Resin
Fmoc-deprotectson of the loaded amino acid was carried out by washing the resin using 15-25 % piperidine in DMF two times for 5 and 10 min. followed by the resin was washed with 3-5*8 v 0.01 - 0.1 M HOBt in DMF. The Fmoc-Thr('Bu)-OH (2.0 - 4,0 eq.), was coupled using coupling agents such as HBTU, COMU, DEPBT, and DIC, preferably DEPBT (2.0 -4,0 eq.) and oxymapure, HOBt, preferably oxymapure (2.0 - 4.0 eq.) and DIPEA, NMM, TM.P, preferably DIPEA (5.0 -8.0 eq.) and MgCb, ZnCk, preferably MgCb (0,01 — 0,1 eq) and DMF/NMP mixture as solvent. The reaction was performed in nitrogen atmosphere and at an elevated temperature around 30-45 °C. Upon completion of coupling of the amino acid confirmed by Kaiser Test, the excess reagents were drained and washed the peptidyl resin with 3 x 10 v DMF.
Stage-28: Synthesis of Fraoc-Gly'"-Thr(tB«)fS-Piien-Thr(tB«)i3-Ser(tBu)!4-
AspCO'BuyS-ViU^SerOBii^-SerCB^
Gln(Trtp-AlaM-AlaH-Lys(Mtt)M^la(OtBu)"-PheM-IJe29-AlaM-Trp(Boc)31-
t Leu32-Vaf3-Arg(Pbf)M~Glyi5-Arg(Pbf)36-Gly3MVangilesii!
Fmoc-deprotection of the loaded amino acid was carried out by washing the resin using 15-25 % piperidine in DMF two times for 5 and 10 min. followed by the resin was washed with 3-5*8 v 0.01 - 0.1 M HOBt in DMF. The Fmoc-Gly-OH (2,0 - 4,0 eq.), was coupled using coupling agents such as HBTU,. COMU, DEPBT, and DiC, preferably
i DEPBT (2.0 -4,0 eq,} and oxymapure, HOBt, preferably oxymapure (2.0 - 4.0 eq.) and DIPEA, NMM, TMP, preferably DIPEA (5,0 - 8.0 eq.) and MgCb, ZnCi2s preferably MgCb (0.01 - 0.1 eq) and DMF/NMP mixture as solvent The reaction was performed in nitrogen atmosphere and at an elevated temperature around 30-45 °C Upon completion of coupling of the amino acid confirmed by Kaiser Test, the excess reagents were drained
I and washed the peptidyl resin with 3 x 10 v DMF.

Stage-29: Synthesis of Faioc-G]u(OtBu)s-<;iy10-Thr(tBu)n-Phe ^-ThtfBup-
SerCBo^-AspCO'BiO'^Val1^
Gly^in(T*0a-AIaM-AIa2M^^
TrpfBoc^^Leu^-VaF-ArgtPbO^-^ly^-Afg^bfj^-Glj^-WangKesifl
Fffioc-deprotection of the loaded amino acid was carried out by washing the resin using 15-25 % piperidine in DMF two times for 5 and 10 rain, followed by the resin was washed with 3-5*8 v 0.01 - 0.1 M HOBt in DMF. The Frnoc-Giu(0'Bu)-OH (2.0 - 4.0 eq.), was coupled using coupling agents such as HB7U, COMU, DEPBT, and DIG, preferably DEPBT (2.0 -4.0 eq.) and oxymapure, HOBt, preferably oxymapure (2.0 ~ 4.0 eq.) and DIPEA, NMM, TMP, preferably DIPEA (5,0 -8.0 eq.) and MgC'b, ZnCh, preferably MgCb (0,01 - 0.1 eq) and DMF/NMP mixture as solvent. The reaction was performed in nitrogen atmosphere and at an elevated temperature around 30-45 "C. Upon completion of coupling of the amino acid confirmed by Kaiser Test, the excess reagents were drained and washed the peptidy! resin with 3 x 10 v DMF.
Stage-30: Synthesis of Fmoc-AIas~Giu(P'Bu)9-G!y10-Th^ SertfcB),4-Asp(0*Buys-VaIJ6~^r(^
Gly22-Gin(Trt)2;Wya24~Ala3M,ys^^^^^ T^BocfM.eir^-Vai^
Fmoe-deprotection of the loaded amino acid was carried out by washing the resin using 15-25 % piperidine in DMF two times for 5 and 10 min. followed by the resin was washed with 3-5*8 v 0.01 - 0.1 M HOBt in DMF. The Fmoc-Ala-OH (2.0 - 4.0 eq.), was coupled using coupling agents such as HBTU, COMU, DEPBT,, and DIG, preferably DEPBT (2.0 -4,0 eq.) and oxymapure, HOBt, preferably oxymapure (2.0 - 4.0 eq.) and DIPEA, NMM, TMP, preferably DIPEA (5.0 -8,0 eq.) and MgCE, ZnCb, preferably MgCb (0,01 - 0.1 eq) and DMF/NMP mixture as solvent. The reaction was performed in nitrogen, atmosphere and r.t. Upon completion of coupling of the amino acid confirmed by Kaiser Test, the excess reagents were drained and. washed the peptidyi resin with 3 x 10 v DMF.
Stage-31: Synthesis of Boo-His{Trt)7-Ala8-G{u(OtB«)9-GIy,0-Thr{*Bu)1 '-Piie'2-TiHtiB«)t3~Ser(tBi0i4--Asp(OtBw)iM^ali^er((Bu)I7~Ser(tBu)iM>'r«,B«)i*-LeHJt>-

CIu(OtBu)2,^Iy2I-^ln(Trt)23-AlaM-AIaIS-Lys(Mtt)iM;iu(OtBH)"-PheM-I]eI9~ Ala^-TrpCBoc^'-Lc^^VaF-ArgCPbfJ^^ly^-ArgCPbf^MJl^-Wang Resin
Frnoc-deprotection of the loaded amino acid was carried out by washing the resin using 15-25 % piperidine in DMF two times for 5 and 10 mm. fallowed by the resin was washed with 3-5*8 v 0.01 - 0.1 M HOB! in DMF. The 8oc-His(Tri)-OH (3.0 - 5.0 eq.), was coupled using coupling agents Such as HBTU, COMU, DEPBT, and D1C, preferably DEPBT (3.0 -5.0 eq.) and oxymapure, HOBt, preferably oxymapure (3.0 - 5.0 eq.) and DIPEA, NMiVl IMP, preferably D1PEA (6.0 -10.0 eq.) and MgCI-2, ZnCh, preferably MgCb (0.01 - 0.1 eq) and DMF/NMP mixture as solvent. The reaction was performed in nitrogen atmosphere and r.t. Upon completion of coupling of the amino acid confirmed by Kaiser Test, the excess reagents were drained and washed the peptidyl resin with 3 x 10 v DMF.
Stage-32: Synthesis of Boc-His(Trt)7-A!a8-GIu(OtBH)9--GIy,0~Thr(*B»),1--Phe11-
Th.r(tBu)l3-«er(tBii)14--Asp(OtBu),s-Va!, 60.0 %}.

Example 8: Purification of Liraglutide
Crude liraglutide was dissolved in dilute ammonium carbonate solution containing 5 -40% ACN at a. concentration of 5-75 mg/ml and was loaded onto pre-equilibrated 100-10-C8 column (10mm x 25.0mm). This was followed by 0.2 CV of the diluent. The bound liraglutide was eluted using a step gradient of the mobile phase (A: 0.1% TFA in water; B: 0.i% TFA. in ACN: IP A). Fractions having purity >92% was concentrated under vacuum followed by isoelectric point precipitation. The precipitate was recovered by sentrifugation, The recovered precipitate was again subjected to another RP-HPLC step an the column 100-10-G8 column (10mm x 250mm). The bound liraglutide was eluted using gradient elution of the mobile phase composed of viz. A: dilute ammonium acetate; B: ACN. Fractions >98.5% were pooled, concentrated under vacuum, precipitated at iso-siectric point & finally lyophilized.
Example 9: Purification of Liraglutide
Crude liraglutide was dissolved in dilute ammonia solution at a concentration, of 10-75 tng/rnl and was subjected to RP-HPLC-1 step on a 1QQ-10-CS column (10mm x 250.mm). This was followed by 0.2 CV of the diluent. The bound liraglutide was eluted using a step gradient of the mobile phase (A: 0,1% TFA in water; B: 0.1% TFA in ACN: IPA). Fractions having purity >90% was concentrated under vacuum followed by iso-eiectric point precipitation. The precipitate was recovered by cenirifugation. The recovered precipitate was again subjected to a RP-HPLC-2 step on the column 100-10-CS column [10mm x 250mm), The bound liraglutide was eiuted using gradient elution of the mobile phase composed of viz. A: TFA in water; B: TFA in Methanol. This step helped in reduction of a specific impurity. Fractions >93% were pooled, diluted with ammonium acetate and loaded onto RP-HPLC-3 step on the column 100-10-C8 column (TOmm x

250mm). "The bound iiragiutide was eluted using gradient elution of the mobile phase composed of viz. A: Ammonium acetate; B; ACN. Fractions >98.5% were pooled, concentrated under vacuum, precipitated at iso-eiectric point & finally lyophilized.

1. A process for the preparation of liragiutide comprising the steps of,
a) Loading of C-terminai glycine to a resin solid-phase support in the presence of coupling agent.
b) Capping of the unreacted functional sites,
c) Sequential, coupling of N"- and side chain protected amino acids to prepare backbone of iiragUrtide, in the presence of coupling agent and an inorganic salt.
d) Deprotection of side chain protecting group, of lysine.
e) Coupling of glutamic acid ant! palmitic acid to the side chain of lysine in the presence of coupling agent and fan inorganic salt.
f) Crude liragiutide is obtained by removal of protective groups and cleavage of peptide from the resin.
g) Optionally purifying crude liragiutide,
2. The process for the preparation of liragiutide according to the claim 1, comprising the
steps of,
a) Loading of C-terminal glycine to a resin solid-phase support in the presence of coupling agent.
b) Capping of the unreacted functional sites were carried out using acetic anhydride and organic base
c) Sequential coupling of N"- and side chain protected amino acids to prepare backbone of liragiutide, in the presence of coupling agent and an inorganic salt.
d) Deprotection of side chain protecting group of lysine.
e) Coupling of glutamic acid and palmitic acid in sequential, manner to the side chain of lysine in the presence of coupling agent and an inorganic salt.
f) Crude liragiutide is obtained by removal of protective groups and cleavage of peptide from the resin.
g) Optionally purifying crude IiragUrtide.
3. A process for the preparation of liragiutide comprising the steps of,

a) Coupling of Nu-Fmoc-p.rotected glycine (Fmoc-Gly-QH) to a resin solid-phase support in the presence of coupling agent.
b) Sequential coupling of N°- and side chain protected amino acids to prepare backbone of liraglutide, in the presence of coupling agent and an inorganic salt.
c) Deproiection of side chain protecting group of lysine,
d) Coupling of palmitoyi-giutamic acid (Pal-Glu- O'Bu) side chain to the side chain of lysine in the presence of coupling agent and an inorganic salt.
e} Crude liraglutide h obtained by removal of protective groups and cleavage of peptide from the resin.
f) Optionally purifying crude liraglutide. k The process for the preparation of liraglutide according to the claim 3, comprising the teps of,
a) Coupling of Na-Fmoc-protected glycine (Fmoc-Gly-OM) to a resin solid-phase support in the presence of coupling agent.
b) Sequential coupling of N™- and side chain protected amino acids to prepare backbone of liraglutide, in the presence of coupling agent and an inorganic salt.
c) Deprotection of side chain methyltrityl protecting group of lysine using TFA in dichloromethane,
d) Coupling of palmitoyi-giutamic acid (Pal-Glu-O'Bu) side chain to the side chain of lysine in the presence of coupling agent HBTU, COMU, DEPBT. DIG and additives oxymapure, HOBt. or a combination of coupling agents/additives thereof and an inorganic salt.
e) Crude liraglutide is obtained by removal of protective groups and cleavage of peptide from the resin.
ft Optionally purifying crude liraglutide. i. The process for the preparation of liraglutide comprising the steps of,
a} Coupling of A,r" -Fmoc-protected glycine (Fmoc-Gly-OH) to a resin solid-phase support in the presence of coupling agent.
b) Sequential coupling of Net- and side chain protected amino acids to prepare backbone of liraglutide, in the presence of coupling agent and an inorganic salt.
c) Deprotection of Frnoc group of each loaded amino acid using piperidine in DMF or piperidine/DBU/DMF mixture.

d) After each Fmoc deprotection step washing step using HOBt in DMF,
e) Deprotection of methyltrHyl protecting group of lysine.
f) Coupling of paSmiioyi-glutaraic acid ester (Pai-Glu-O'Bu) side chain to the side chain of lysine in the presence of coupling agent arid an inorganic salt.
g) Crude liraglutide is obtained by removal of protective groups and cleavage of peptide from the resin.
h) Optionally purifying crude liraglutide.
6. The process for the preparation of liraglutide according to claim 5, comprising the steps
ot;
a) Coupling of Na-Fmoc-proteeted glycine (Fraoc-Gly-OH) to a resin solid-phase support in the presence of coupling agent.
b) Sequential coupling of W- and side chain protected amino acids to prepare backbone of liraglutide, in the presence of coupling agent and an Inorganic salt.
c) Deprotection of Fmoc group of each loaded amino acid using piperidine in DMF or piperidine/DBU/DMF mixture.
d) After each Fmoc deprotection step washing step using HOBt in DMF.
e) Deprotection of side chain. Methyltrityl protecting group of lysine using HFIP/TES/TFE/MDG.
f) Coupling of palmitoyl-giutamic acid (Pal-GJii-O'Bu) side chain to the side chain of lysine in the presence of coupling agent and an inorganic salt.
g) Crude liraglutide is obtained by removal of protective groups and cleavage of peptide from the resin.
h) Optionally purifying crude liraglutide.
7. The process for the preparation of liraglutide comprising the steps of,
a) Coupling of Nu-Fmoc-protected glycine (Fmoe-Gly-QH) to a resin solid-phase
support in the presence of coupling agent. h) Sequential coupling of Na- and side chain protected amino acids to prepare
backbone of liraglutide, in the presence of coupling agent and an inorganic salt, c) Deprotection of Fmoc group of each loaded amino acid using piperidine in DMF
or piperidine/DBU/DMF mixture.

d) After each Fmoc deprotection step washing step using HOBt in DMF.
e) Deprotection of Methyltrityl protecting group of lysine.
f) Coupling of protected glutamic acid and palmitic acid in sequential manner to the side chain of lysine in the presence of coupling agent and an inorganic salt.
g) Crude iiragiutide is obtained by removal of protective groups and cleavage of peptide from the resin.
h) Optionally purifying crude Iiragiutide.
8. The process for the preparation of iiragiutide according to claim 7, comprising the steps
of,
a) Coupling of N"-Fmoc-protected glycine (Fmoe-Gly-OH) to a resin solid-phase support in the presence of coupling agent,
b) Sequential coupling of Ntt- and side chain protected amino acids to prepare backbone of Iiragiutide, in the presence of coupling agent and an inorganic salt.
c) Deprotection of Fmoc group of each loaded amino acid using piperidine in DMF or piperidine/DBUTJMF mixture,
d) After each Fmoc deprotection step washing step using HOBt in DMF.
e) Deprotection of Methyltrityl protecting group of lysine using HFIP/TES/TFE/MDC.
i) Coupling of protected ■y-glutamic acid and palmitic acid in sequential manner to the side chain of lysine in the presence of coupling agent and an inorganic salt.
g) Crude iiragiutide is obtained by removal of protective groups and. cleavage of peptide from the resin.
h) Optionally purifying crude Iiragiutide.
9. The process for preparation of Iiragiutide according to any of the claims above
involving coupling agents selected from HBTU, COMU, DEPBT, DiC or any
combination thereof.
10. The process for preparation of Iiragiutide according to any of the claims above
involving coupling additives selected from oxyrnapure, HOBt or any combination thereof.
11. The process for preparation of iiragiutide comprising, coupling of Boe-Histidine using
a coupling agent mixture selected from HBTU-oxyma pure, COMU-oxyma pure,
DEFBT-oxynm pure or DIC-oxyma pure.

12. The process for preparation of Uragtutide according to claim II. coupling of Boc-Histidine using DEPBT-oxyma pure.
13. The process for preparation ofliragiuti.de comprising, deprotectiors of Methyitrit/1 protecting group of lysine using HFiP/'TES/ITE/MDC.
5 14. The process for preparation of liragiutide comprising coupling of amino acids 9 to 13 using an elevated temperature.
15, The process for preparation of liraglutide according to claim 14, comprising coupling of amino acids 9 to 13 at a temperature from 30-45 °C.