TECHNICAL FIELD OF THE INVENTION:
The present invention relates to an improved and industrially advantageous process for preparation of Colesevelam hydrochloride, a compound of formula (I).
BACKGROUND OF THE INVENTION:
Colesevelam hydrochloride is a non-absorbed, polymeric, lipid-lowering and glucose-lowering agent intended for oral administration. Colesevelam hydrochloride is a high-capacity bile acid-binding molecule. Colesevelam hydrochloride has been approved by FDA and is sold under the brand name Welchol®.
Colesevelam hydrochloride is poly (allylamine hydrochloride) cross-linked with epichlorohydrin and alkylated with 1-bromodecane and (6-bromohexyl)-trimethylammonium bromide.
U.S. Pat. No. 5,693,675 describes the preparation of Colesevelam. The process involves reacting azobis(amidinopropane) dihydrochloride with allylamine, wherein azobis(amidinopropane) dihydrochloride was present in an amount of 0.4% by weight of allylamine. Further, the process consists of cross-linking polyallylamine hydrochloride with epichlorohydrin, followed by alkylating the resulting cross-linked polyallylamine with 6-bromohexyl trimethylammonium bromide and 1-bromodecane. Colesevelam thus obtained is dried in a vacuum oven at 50° C.
U.S. Pat. No. 5,607,669 disclosed the preparation of Colesevelam, wherein the process involves reacting azobis(amidinopropane) dihydrochloride with allylamine, wherein azobis (amidinopropane) dihydrochloride was present in an amount of 0.4% by weight of allylamine. Further, the process consists of cross-linking polyallylamine hydrochloride with

epichlorohydrin, followed by alkylating the resulting cross-linked polyallylamine with 6-bromohexyl trimethylammonium bromide and 1-bromodecane. Colesevelam thus obtained is dried in an air drying oven at 60° C.
In addition to the above prior art references, process for preparation of colesevelam had also been described in U.S. Pat. Nos. 7,399,821, 7,105,631, 7,148,319, 8,710,154 and 9,475,891, which are incorporated by references.
There is need for an efficient process for preparing colesevelam and hydrochloride salt thereof with higher yields and with higher purity of the final product.
The process of the present invention has advantages of improved yield and increased productivity. The process is also industrially scalable and cost effective.
SUMMARY OF THE INVENTION:
The present invention provides a process for preparation of Colesevelam hydrochloride, a compound of formula I,
comprising:
a) reacting allylamine, a compound of formula A, with azobis(amidinopropane) dihydrochloride, a compound of formula B, to obtain poly(allylamine) hydrochloride, a compound of formula C;
b) reacting poly(allylamine) hydrochloride, a compound of formula C, with epichlorohydrin, a compound of formula D, to obtain a polymer of 2-propen-l-amine with (chloromethyl)oxirane, a compound of formula E; and

c) reacting polymer of 2-propen-l -amine with (chloromethyl)oxirane, a compound of formula E, with 6-bromohexyltrimethylammonium bromide, a compound of formula F, and 1-bromodecane, a compound of formula G, to obtain Colesevelam hydrochloride, a compound of formula I;
An object of the present invention provides a process for the preparation of colesevelam hydrochloride that has improved yield, increased productivity, industrial scalability and cost effectiveness.
It has been surprisingly found that the process according to the present invention have superior yield, increased productivity, industrial scalability and cost effectiveness.
BRIEF DESCRIPTION OF THE DRAWINGS
Figure 1 is an IR spectrum of the colesevelam hydrochloride as obtained in example 3.
DETAILED DESCRIPTION OF THE INVENTION
The present invention provides a process for preparation of Colesevelam hydrochloride, a compound of formula I,

comprising:
a) reacting allylamine, a compound of formula A, with azobis(amidinopropane) dihydrochloride, a compound of formula B, to obtain poly(allylamine) hydrochloride, a compound of formula C;
b) reacting poly(allylamine) hydrochloride, a compound of formula C, with epichlorohydrin, a compound of formula D, to obtain a polymer of 2-propen-l-amine with (chloromethyl)oxirane, a compound of formula E; and
c) reacting polymer of 2-propen-l-amine with (chloromethyl)oxirane, a compound of formula E with 6-bromohexyltrimethylammonium bromide, a compound of formula F, and 1-bromodecane, compound of formula G, to obtain Colesevelam hydrochloride, a compound of formula I.

In one embodiment, step (a) comprises treating a compound of formula A with hydrochloric acid at about 0°C to 20°C, preferably at about 0°C to 15°C. The reaction mixture is distilled out under vacuum below 65°C, degassed and cooled to about 25°C to 40°C, preferably to about 35°C to 40°C. In yet another embodiment, temperature of the reaction mixture obtained is raised to about 45°C to 55° C. Azobis(amidinopropane) dihydrochloride suspended in water is then added to the reaction mixture at about 45°C to 55°C.
In one embodiment, the amount of compound of formula B used is about 10% w/w to 20% w/w with respect to amount of compound of formula A used, preferably about 12% w/w to 18% w/w with respect to amount of compound of formula A used, more preferably about 14% w/w to 16%o w/w with respect to amount of compound of formula A used. In yet another embodiment, amount of compound of formula B used is about 15% w/w with respect to amount of compound of formula A used. For example, if 100 g of compound of formula A is used then 15 g of compound of formula B is used in step (a), which is equal to 15 % w/w with respect to amount (100 g) of compound of formula A used. The reaction mixture may be optionally stirred and maintained to obtain a viscous mass.
After completion of the reaction in step (a), suitable work up may be performed, as known to a skilled artisan, to isolate the compound of formula C before step (b). In one embodiment, the hot viscous reaction mass as obtained above is treated with methanol, optionally under stirring under nitrogen atmosphere at about 25°C to 30°C. The obtained product is then filtered under vacuum and nitrogen atmosphere at about 25°C to 30°C, washed with methanol and dried under vacuum at about 50°C to 55°C under nitrogen atmosphere.
In one embodiment, step (a) comprises reacting a compound of formula A with a compound of formula B, wherein the amount of compound of formula B used is about 10%) w/w to 20% w/w with respect to amount of compound of formula A used, preferably about 12% w/w to 18%

w/w with respect to amount of compound of formula A used, more preferably about 14% w/w to 16% w/w with respect to amount of compound of formula A used.
In one embodiment, step (a) comprises reacting a compound of formula A with a compound of formula B, wherein the amount of compound of formula B used is about 15% w/w with respect to amount of compound of formula A used.
Surprisingly, it has been found out by the present inventors that, use of compound of formula B in an amount of about 10% w/w to 20% w/w with respect to amount of allylamine, preferably about 12% w/w to 18%) w/w with respect to amount of compound of formula A used, more preferably about 14% w/w to 16% w/w with respect to amount of compound of formula A used leads to increase in yield as compared to prior art. processes. In another embodiment, amount of compound of formula B used is about 15% w/w with respect to amount of compound of formula A used. The use of such amounts of formula B, gives increased yield of compound of formula C and compound of formula I, as compared to the prior art processes. The yield of compound of formula C with the process disclosed in U.S. Pat. No. 5,693,675 is 0.86 times w/w with respect to amount of allylamine, whereas the process of the current invention provides a yield of 1.5 times w/w with respect to amount of allylamine used.
In one embodiment, present invention provides a process for preparation of Colesevelam hydrochloride, a compound of formula I, comprising reacting allylamine, a compound of formula A with azobis(amidinopropane) dihydrochloride, a compound of formula B, in presence of hydrochloric acid to obtain poly(allylamine) hydrochloride, a compound of formula C, wherein the azobis(amidinopropane) dihydrochloride, a compound of formula B is used in an amount of about 10% w/w to 20% w/w with respect to amount of compound of formula A used, preferably about 12% w/w to 18% w/w with respect to amount of compound of formula A used, more preferably about 14% w/w to 16% w/w with respect to amount of compound of formula A used.
In one embodiment, present invention provides a process for preparation of Colesevelam hydrochloride, a compound of formula I, comprising reacting allylamine, a compound of formula A with azobis(amidinopropane) dihydrochloride, a compound of formula B, in presence of hydrochloric acid to obtain poly(allylamine) hydrochloride, a compound of formula C, wherein the azobis(amidinopropane) dihydrochloride, a compound of formula B is used in an amount of about 15% w/w with respect to amount of compound of formula A used.

In one embodiment, present invention provides a process for preparation of Colesevelam hydrochloride, a compound of formula I, comprising reacting allylamine, a compound of formula A with azobis(amidinopropane) dihydrochloride, a compound of formula B, in presence of hydrochloric acid at a temperature of about 45°C to 55°C to obtain poly(allylamine) hydrochloride, a compound of formula C.
In one embodiment, present invention provides a process for preparation of Colesevelam hydrochloride, a compound of formula I, comprising reacting allylamine, a compound of formula A with azobis(amidinopropane) dihydrochloride, a compound of formula B, in presence of hydrochloric acid at a temperature of about 45°C to 55°C to obtain poly(allylamine) hydrochloride, a compound of formula C, wherein the azobis(amidinopropane) dihydrochloride, a compound of formula B is used in an amount of about 10% w/w to 20% w/w with respect to amount of compound of formula A used, preferably about 12% w/w to 18% w/w with respect to amount of compound of formula A used, more preferably about 14% w/w to 16%o w/w with respect to amount of compound of formula A used.
In one embodiment, present invention provides a process for preparation of Colesevelam hydrochloride, a compound of formula I, comprising reacting allylamine, a compound of formula A with azobis(amidinopropane) dihydrochloride, a compound of formula B, in presence of hydrochloric acid at a temperature of about 45°C to 55°C to obtain poly(allylamine) hydrochloride, a compound of formula C, wherein the azobis(amidinopropane) dihydrochloride, a compound of formula B is used in an amount of about 15% w/w with respect to amount of compound of formula A used.
In one embodiment, present invention provides a process for preparation of poly(allylamine) hydrochloride, a compound of formula C, comprising reacting allylamine, a compound of formula A with azobis(amidinopropane) dihydrochloride, a compound of formula B, in presence of hydrochloric acid, wherein the azobis(amidinopropane) dihydrochloride, a compound of formula B is used in an amount of about 10% w/w to 20% w/w with respect to amount of compound of formula A used, preferably about 12% w/w to 18% w/w with respect to amount of compound of formula A used, more preferably about 14% w/w to 16% w/w with respect to amount of compound of formula A used.
In one embodiment, present invention provides a process for preparation of poly(allylamine) hydrochloride, a compound of formula C, comprising reacting allylamine, a compound of formula A with azobis(amidinopropane) dihydrochloride, a compound of formula B, in

presence of hydrochloric acid, wherein the azobis(amidinopropane) dihydrochloride, a compound of formula B is used in an amount of about 15% w/w with respect to amount of compound of formula A used.
In one embodiment, present invention provides a process for preparation of compound of formula C comprising, reacting a compound of formula A with a compound of formula B, in presence of hydrochloric acid at a temperature of about 45°C to 55°C to obtain a compound of formula C.
In one embodiment, present invention provides a process for preparation of poly(allylamine) hydrochloride, a compound of formula C, comprising reacting allylamine, a compound of formula A with azobis(amidinopropane) dihydrochloride, a compound of formula B, in presence of hydrochloric acid at a temperature of about 45°C to 55°C, wherein the azobis(amidinopropane) dihydrochloride, a compound of formula B is used in an amount of about 10% w/w to 20%o w/w with respect to amount of compound of formula A used, preferably about 12% w/w to 18% /w with respect to amount of compound of formula A used, more preferably about 14% w/w to 16% w/w with respect to amount of compound of formula A used.
In one embodiment, present invention provides a process for preparation of poly(allylamine) hydrochloride, a compound of formula C, comprising reacting allylamine, a compound of formula A with azobis(amidinopropane) dihydrochloride, a compound of formula B in presence of hydrochloric acid at a temperature of about 45°C to 55°C, wherein the azobis(amidinopropane) dihydrochloride, a compound of formula B is used in an amount of about 15% w/w with respect to amount of compound of formula A used.
In one embodiment, step (b) comprises treating compound of formula C with water at about 20°C to 40°C, preferably at about 25°C to 30°C to get clear solution. Suitable base is added, optionally under stirring, to the reaction mass obtained. Suitable bases may be selected from bases such as alkali and alkaline metal hydroxides, carbonates, bicarbonates etc. In another embodiment, the suitable base used is aq. sodium hydroxide. The reaction mass is then filtered. In yet another embodiment, to the reaction mass, epichlorohydrin is added, optionally under stirring, to obtain swelled jelly mass. Stirring may be stopped and reaction is maintained for 15 to 20 h, at same temperature.
After completion of the reaction in step (b), suitable work up may be performed, as known to a skilled artisan, to isolate the compound of formula E before step (c). In one embodiment, the

jelly mass obtained is crushed and water is added to the crushed jelly mass and stirring was done at about 25°C to 30°C. The reaction mixture is filtered and the wet cake obtained is washed with water and dried, optionally the water washing process may be repeated for 2-3 times. The obtained wet solid is treated with C1-C4 alcohols, preferably isopropyl alcohol, then filtered and dried at about 50°C to 70°C.
In one embodiment, step (c) comprises reacting compound of formula E with a compound of formula F and compound of formula G in presence of C1-C4 alcohol, preferably methanol, at about 60°C to 70°C, preferably at about 65 °C to 70°C. Suitable base is added, optionally under stirring, to the reaction mass obtained. Suitable bases may be selected from bases such as alkali and alkaline metal hydroxides, carbonates, bicarbonates etc. In yet another embodiment, the suitable base used is aq. sodium hydroxide. Sodium hydroxide is added, at about 60°C to 70°C, preferably at about 65°C to 70°C. Optionally sodium hydroxide may be added lot wise. Reaction mixture is cooled to about 20°C to 40°C, preferably to about 25°C to 30°C and hydrochloric acid is added.
After completion of the reaction in step (c), suitable work up may be performed, as known to a skilled artisan, to isolate the compound of formula I. In one embodiment, the reaction mixture is filtered and the obtained wet cake is washed with C1-C4 alcohol, preferably methanol and dried under vacuum, optionally the process may be repeated. Sodium chloride solution is added to the obtained wet material and optionally stirred at about 25°C to 30°C for about lh, then filtered and washed with water, optionally the sodium chloride washing step may be repeated for 2-4 times. The obtained wet cake is treated with water, optionally under stirring at about 25°C to 30°C. The obtained product is filtered and washed with water, the process may be repeated for 2-3 times. The obtained wet cake is treated with C1-C4 alcohol, preferably isopropyl alcohol, optionally under stirring for lh. The obtained product is then filtered, washed with C1-C4 alcohol, preferably isopropyl alcohol and dried at about 50°C to 70°C.
In one embodiment, the present invention provides a process for preparation of Colesevelam
hydrochloride, a compound of formula I, comprising:
a) reacting allylamine, a compound of formula A with azobis(amidinopropane) dihydrochloride, a compound of formula B to obtain poly(allylamine) hydrochloride, a compound of formula C, wherein the azobis(amidinopropane) dihydrochloride, a compound of formula B is used in an amount of about 10% w/w to 20% w/w with respect to amount of compound of formula A used, preferably about 12% w/w to 18% w/w with

respect to amount of compound of formula A used, more preferably about 14% w/w to 16% w/w with respect to amount of compound of formula A used;
b) reacting poly(allylamine) hydrochloride, a compound of formula C with epichlorohydrin, a compound of formula D to obtain a polymer of 2-propen-l -amine with (chloromethyl)oxirane, a compound of formula E; and
c) reacting polymer of 2-propen-l-amine with (chloromethyl)oxirane, a compound of formula E with 6-bromohexyltrimethylammonium bromide, a compound of formula F and 1-bromodecane, a compound of formula G to obtain Colesevelam hydrochloride, a compound of formula I.
In one embodiment, the present invention provides a process for preparation of Colesevelam hydrochloride, a compound of formula I, comprising:
a) reacting allylamine, a compound of formula A with azobis(amidinopropane) dihydrochloride, a compound of formula B to obtain poly(allylamine) hydrochloride, a compound of formula C, wherein the azobis(amidinopropane) dihydrochloride, a compound of formula B is used in an amount of about 15% w/w with respect to amount of compound of formula A used;
b) reacting poly(allylamine) hydrochloride, a compound of formula C with epichlorohydrin, a compound of formula D to obtain a polymer of 2-propen-l-amine with (chloromethyl)oxirane, a compound of formula E; and.
c) reacting polymer of 2-propen-l-amine with (chloromethyl)oxirane, a compound of formula E with 6-bromohexyltrimethylammonium bromide, a compound of formula F and 1-bromodecane, a compound of formula G to obtain Colesevelam hydrochloride, a compound of formula I.
In one embodiment, the present invention provides a process for preparation of Colesevelam hydrochloride, a compound of formula I, comprising:
a) reacting allylamine, a compound of formula A with azobis(amidinopropane) dihydrochloride, a compound of formula B in presence of hydrochloric acid at a temperature of about 45°C to 55°C to obtain poly(allylamine) hydrochloride, a compound of formula C;
b) reacting poly(allylamine) hydrochloride, a compound of formula C with epichlorohydrin, a compound of formula D in presence of sodium hydroxide to obtain polymer of 2-propen-1-amine with (chloromethyl)oxirane, a compound of formula E;

c) reacting polymer of 2-propen-l-amine with (chloromethyl)oxirane, a compound of formula E with 6-bromohexyltrimethylammonium bromide, a compound of formula F and 1-bromodecane, a compound of formula G to obtain Colesevelam hydrochloride, a compound of formula I.
In one embodiment, the present invention provides a process for preparation of Colesevelam hydrochloride, a compound of formula I, comprising:
a) reacting allylamine, a compound of formula A with azobis(amidinopropane) dihydrochloride, a compound of formula B in presence of hydrochloric acid at a temperature of about 45 °C to 55°C to obtain poly(allylamine) hydrochloride, a compound of formula C, wherein the azobis(amidinopropane) dihydrochloride, a compound of formula B is used in an amount of about 10% w/w to 20% w/w with respect to amount of compound of formula A used, preferably about 12% w/w to 18%) w/w with respect to amount of compound of formula A used, more preferably about 14% w/w to 16%) w/w with respect to amount of compound of formula A used;
b) reacting poly(allylamine) hydrochloride, a compound of formula C with epichlorohydrin, a compound of formula D in presence of sodium hydroxide to obtain polymer of 2-propen-1-amine with (chloromethyl)oxirane, a compound of formula E;
c) reacting polymer of 2-propen-l-amine with (chloromethyl)oxirane, a compound of formula E with 6-bromohexyltrimethylammonium bromide, a compound of formula F and 1-bromodecane, a compound of formula G to obtain Colesevelam hydrochloride, a compound of formula I.
In one embodiment, the present invention provides a process for preparation of Colesevelam hydrochloride, a compound of formula I, comprising:
a) reacting allylamine, a compound of formula A with azobis(amidinopropane) dihydrochloride, a compound of formula B in presence of hydrochloric acid at a temperature of about 45 °C to 55°C to obtain poly(allylamine) hydrochloride, a compound of formula C, wherein the azobis(amidinopropane) dihydrochloride, a compound of formula B is used in an amount of about 15% w/w with respect to amount of compound of formula A used;
b) reacting poly(allylamine) hydrochloride, a compound of formula C with epichlorohydrin, a compound of formula D in presence of sodium hydroxide to obtain polymer of 2-propen-1-amine with (chloromethyl)oxirane, a compound of formula E;

c) reacting polymer of 2-propen-l-amine with (chloromethyl)oxirane, a compound of formula E with 6-bromohexyltrimethylammonium bromide, a compound of formula F and 1-bromodecane, a compound of formula G to obtain Colesevelam hydrochloride, a compound of formula I.
In one embodiment, the present invention provides a process for preparation of Colesevelam
hydrochloride, a compound of formula I, comprising:
a) reacting allylamine, a compound of formula A with azobis(amidinopropane) dihydrochloride, a compound of formula B in presence of hydrochloric acid at a temperature of about 45°C to 55°C to obtain poly(allylamine) hydrochloride, a compound of formula C wherein the azobis(amidinopropane) dihydrochloride, a compound of formula B is used in an amount of about 15% w/w with respect to amount of compound of formula A used;
b) reacting poly(allylamine) hydrochloride, a compound of formula C with epichlorohydrin, a compound of formula D in presence of sodium hydroxide to obtain polymer of 2-propen-1-amine with (chloromethyl)oxirane, a compound of formula E;
c) reacting polymer of 2-propen-l-amine with (chloromethyl)oxirane, a compound of formula E, with 6-bromohexyltrimethylammonium bromide, a compound of formula F and 1-bromodecane, a compound of formula G in presence of methanol and sodium hydroxide at a temperature of about 60°C to 70°C to obtain Colesevelam hydrochloride, a compound of formula I.
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 included within the scope of the present invention.
The present invention is explained in detail by referring to examples, which are not to be construed as limitative.
Example-1: Preparation of Poly (allylamine) hydrochloride (Compound C)
Concentrated HC1 (191.8 g, 1.83 moles) was added to a round bottom flask at about 0°C to 15°C and allylamine (100 g, 1.75 moles) was added to it in a dropwise manner at about 0°C to 15°C and stirred. Reaction mixture was distilled out under vacuum below 65°C, degassed and cooled to about 35°C to 40°C. Water was added and the reaction mixture obtained was stirred at about 25 °C to 40°C to get a clear solution. Nitrogen was purged in reaction mixture and the temperature was raised to about 48°C to 52°C. Azobis (amidinopropane) dihydrochloride (15 g, 0.055 moles) was suspended in 31.5 mL of water at about 48°C to 52°C. Reaction was

maintained at about 48°C to 52°C for about 65 to 70 h (reaction mass became viscous). Methanol (2000 mL) was taken in another flask and hot viscous reaction mass obtained was added slowly into the flask containing methanol, with stirring under nitrogen atmosphere (reaction mass was initially sticky but, became free under stirring). Reaction mixture was stirred under nitrogen atmosphere at about 25 °C to 30°C. Product obtained was filtered under vacuum and nitrogen atmosphere at about 25°C to 30°C. Wet cake obtained was washed with methanol and dried under vacuum in nitrogen atmosphere. The wet cake obtained (Wet weight: 250.2 g) was dried in preheated vacuum oven at about 50°C to 55 °C for about 15 to 20 h. Product was unloaded under nitrogen atmosphere. (Dry Weight: 153.5 g; Yield: 140 to 160 g). Example-2: Preparation of polymer of 2-Propen-l-amine with (chloromethyl) oxirane (Compound E)
150 mL of water was taken in a round bottom flask and polyallylamine hydrochloride (50.0 g) was added lot wise to it under stirring at about 25 °C to 30°C and stirred to obtain a clear solution. To the reaction mixture obtained, sodium hydroxide solution (14.18 g, 0.355 moles of NaOH dissolved in 50.0 mL of water) was added at about 25°C to 30°C and stirred. Epichlorohydrin (2.95 g, 0.031 moles) was added to the reaction mixture and stirred. Thick swelled jelly mass was formed. The reaction mass was maintained as such at about 25°C to 30°C for about 18 to 20 hours . Jelly mass obtained was gently crushed, water was added to it and the reaction mass obtained was stirred vigorously at about 25°C to 30°C. Reaction mixture was filtered and the wet cake obtained was washed with water and dried. The water washing was repeated for another 2 times. The wet solid obtained was stirred with 17 vol of Isopropyl alcohol, filtered and dried in FBD at about 60°Cto65°C. The material was ground and dried under vacuum at about 60°C to 65°C for about 10 to 12 h. Yield: 33.5 g to 34.5 g. Example-3: Preparation of Colesevelam Hydrochloride (Compound I) Methanol (220 mL) was taken in a round bottom flask and the product obtained in example 2 (10 g) was added to it under stirring at about 25°C to 30°C. 6-Bromohexyltrimehtyl ammonium bromide (16.1 g) and 1-Bromodecane (11.0 g) were added to the reaction mixture and flushed with methanol. The temperature of the reaction mass was raised to about 65°C to 70°C. Aqueous sodium hydroxide (1.12 g of sodium hydroxide dissolved in 1.12 mL of purified water) was charged to the reaction mixture at about 65°C to 70°C, then stirred. This aqueous sodium hydroxide treatment was repeated for another 3 times. The reaction mixture was maintained at about 65°Cto70°C for about 12hours. Reaction was monitored for 1-bromodecane content by Gas Chromatography and 6-Bromohexyltrimehtyl ammonium bromide content by Ion Chromatography. Reaction mixture was cooled to about 25°C to 30°C

and HC1 was added drop wise to it. Reaction mixture obtained was stirred at about 25°C to about 30°C, filtered and the wet cake obtained was with methanol and dried under vacuum. To the wet cake obtained, 200 mL methanol (20 vol) was added and the reaction mixture was stirred at about 25°C to about 30°C. Reaction mixture was filtered and the wet cake obtained was washed with methanol. Aqueous sodium chloride solution was added to wet material and the mass obtained was stirred at about 25 °C to about 30°C, filtered and washed with water. The sodium chloride solution step was repeated for another 3 times. To the wet cake obtained, water was added and the reaction mass obtained was stirred at 25°C to 30°C. Reaction mixture obtained was filtered and the wet cake obtained was washed with water. The water washing step was repeated for 2 more times. Isopropyl alcohol was added to the wet cake obtained and the reaction mixture was stirred, filtered and the wet cake obtained was washed with Isopropyl alcohol and dried. The wet product obtained was dried in FBD at about 60°C to about 65°C. After FBD drying, the material obtained was ground in grinder and dried under vacuum at about 60°C to about 65°C for about 10 to 12 hours. All possible process and degradant impurities were analyzed by Ion chromatography and Gas chromatography. Yield obtained was 22 g to 24 g.
The Colesevelam hydrochloride obtained above provides an infrared spectrum with peaks at 3380.55, 2921.754, 2852.68, 2755.46, 2418.178, 2344.088, 2110.04, 1594.392, 1457.819, 1376.213, 1005.332, 968.260, 910.927, 792.784 and 722.104 cm-1 (FIG. 1).

We claim:
1. A process for preparation of Colesevelam hydrochloride, a compound of formula I,
comprising: a) reacting a allylamine, a compound of formula A, with azobis
(amidinopropane)dihydrochloride, a compound of formula B, to obtain
poly (ally lamine)hydrochloride, a compound of formula C;
b) reacting the compound of formula C with epichlorohydrin, a compound of formula D, to obtain a polymer of 2-propen-l-amine with (chloromethyl)oxirane, a compound of formula E;
c) reacting the polymer of 2-propen-l-amine with (chloromethyl)oxirane, a compound of formula E, with 6-bromohexyltrimethyl ammonium bromide, a compound of formula F, and 1-bromodecane, a compound of formula G, to obtain a compound Colesevelam hydrochloride of formula I

2. The process for preparation of Colesevelam hydrochloride according to claim 1, wherein the amount of compound of formula B used is 10% w/w to 20% w/w with respect to amount of compound of formula A used.
3. The process for preparation of Colesevelam hydrochloride according to claim 1, comprising reacting allylamine, a compound of formula A, with azobis(amidinopropane)
• dihydrochloride, a compound of formula B, in presence of hydrochloric acid, at a temperature of 45°C to 55°C to obtain a compound poly(allylamine) hydrochloride, a compound of formula C, wherein the amount of compound of formula B used is 10% w/w to 20% w/w with respect to amount of compound of formula A used.
4. A process for the preparation of Colesevelam hydrochloride, a compound of formula I,
comprising:
a) reacting allylamine, a compound of formula A, with azobis(amidinopropane) dihydrochloride, a compound of formula B, in presence of hydrochloric acid at a temperature of 45°C to 55°C to obtain poly(allylamine)hydrochloride, a compound of formula C;
b) reacting the compound of formula C with epichlorohydrin, a compound of formula D, in presence of sodium hydroxide to obtain a polymer of 2-propen-l-amine with (chloromethyl)oxirane, a compound of formula E;
c) reacting the compound of formula E with 6-bromohexyltrimethyl ammonium bromide, a compound of formula F, and 1-bromodecane, a compound of formula G, to obtain Colesevelam hydrochloride, a compound of formula (I).
5. A process for the preparation of Colesevelam hydrochloride, a compound of formula I,
comprising
a) reacting allylamine, a compound of formula A, with azobis(amidinopropane) dihydrochloride, a compound of formula B, in presence of hydrochloric acid at a temperature of 45 °C to 55°C to obtain poly(allylamine)hydrochloride, a compound of formula C;
b) reacting the compound of formula C with epichlorohydrin, a compound of formula D, in presence of sodium hydroxide to obtain a polymer of 2-propen-l-amine with (chloromethyl)oxirane, a compound of formula E;
c) reacting the compound of formula E with 6-bromohexyltrimethyl ammonium bromide, a compound of formula F, and 1 -bromodecane, a compound of formula G,

in presence of methanol and sodium hydroxide at a temperature of 60°C to 70°C to obtain Colesevelam hydrochloride of formula (I).
6. A process for preparation of Colesevelam hydrochloride according to claim 4, wherein the amount of compound of formula B used is 10% w/w to 20% w/w with respect to the amount of compound of formula A Used.
7. A process for preparation of Colesevelam hydrochloride according to claim 5, wherein the amount of compound of formula B used is 10% w/w to 20% w/w with respect to the amount of compound of formula A used.
8. A process for the preparation of poly(allylamine)hydrochloride, a compound of formula C, comprising reacting allylamine, a compound of formula A with azobis(amidinopropane) dihydrochloride, a compound of formula B in presence of hydrochloric acid wherein the amount of compound of formula B used is 10% w/w to 20% w/w with respect to the amount of compound of formula A used.
9. A process for the preparation of poly(allylamine)hydrochloride, a compound of formula C, according to claim 8 wherein the reaction is performed at a temperature of 45°C to 55°C.