DESC:PURIFICATION CRYSTALLINE FORM A OF VONOPRAZAN FUMARATE

FIELD OF THE INVENTION

The present invention relates to a purification crystalline form A of Vonoprazan Fumarate with high purity.

BACKGROUND OF THE INVENTION

Vonoprazan Fumarate, chemical entitled 1-[-5(-2-Fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]-N-methylmethanamine mono fumarate. Vonoprazan Fumarate (TAK-438) is a potassium ion-competitive acid blocker with a new mechanism that accumulates in gastric parietal cells and suppresses acid secretion. Its structural formula is as follows:

Vonoprazan Fumarate (TAK-438) was approved by Pharmaceuticals and Medical Devices Agency (PMDA) on December 26, 2014. It was developed by Takeda Pharmaceutical Co. Ltd, marketed as Takecab®.

Vonoprazan Fumarate is reported in US 7977488 B2 by Takeda and its process for preparation, which comprises Vonoprazan residue was purified by basic silica gel column chromatography (eluent: ethylacetate-methanol=1:0?7:3) to give a free salt of Vonoprazan as a pale yellow oil (yield 1.30 g). The obtained free salt of Vonoprazan was dissolved in ethyl acetate (30 mL), a solution of fumaric acid in methanol was added dropwise at room temperature and the obtained crystals were collected by filtration, and washed with ethyl acetate to give the Vonoprazan Fumarate as colorless crystals.
US8822694 discloses purification process of Vonoprazan Fumarate, which comprises by crude Vonoprazan Fumarate was suspended in a mixed solution of methanol and water.

US10538506 discloses purification process of Vonoprazan Fumarate, which comprises by crude Vonoprazan Fumarate was dissolved in a mixture of isopropanol and water or mixture of ethyl acetate and methanol or methanol or water.

The object of the present invention to purification process crystalline Form A of Vonoprazan Fumarate.

In view of the foregoing, the present inventors had developed purification process of crystalline Form A of Vonoprazan Fumarate by using mixture of acetone/water to get high yield and high purity. The aforesaid invention is commercial, eco-friendly and industrial applicable process

OBJECTIVE OF THE INVENTION

The present invention relates to a purification crystalline form A of Vonoprazan Fumarate with high purity and its process comprising.

a. Crude Vonoprazan Fumarate was dissolved in mixture of acetone and water,
b. heating the obtained suspension at suitable temperature,
c. cooling the obtained solution in step b), and
d. isolating the pure crystalline Form A of Vonoprazan Fumarate.

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to a purification crystalline form A of Vonoprazan Fumarate with high purity.

The present invention relates to a purification crystalline Form A of Vonoprazan Fumarate, comprising:

a. Crude Vonoprazan Fumarate was dissolved in mixture of acetone and water,
b. heating the obtained suspension at suitable temperature,
c. cooling the obtained solution in step b), and
d. isolating the pure crystalline Form A of Vonoprazan Fumarate.

According to the embodiment of the present invention, the crude of Vonoprazan Fumarate was dissolved in mixture of acetone and water at 25-30°C. The reaction mass temperature was raised to 40-75°C to get homogenous solution, it was cooled to 0-5°C and filtered. The obtained solid washed with pre-cooled mixture of acetone and purified water to get crystalline Form A of Vonoprazan Fumarate.

Another embodiment of the present invention provides, crystalline Form A of Vonoprazan Fumarate having particle size distribution D90 less than 250 µm, preferably D90 is 10 to 250 µm.

According to an embodiment of the present invention provides crystalline Form A of Vonoprazan Fumarate having HPLC purity = 99.6%.

The process details of the invention are provided in the examples given below, which are provided by way of illustration only and therefore should not be construed to limit the scope of the invention.

EXAMPLES
Purification crystalline Form A of Vonoprazan Fumarate

Example-1:
Vonoprazan fumarate (100 g) was added to a mixture of acetone (800 ml) and water (1000 ml) at 25-30°C and heated to 50-55°C to get homogenous solution, then added activated carbon (5 g) and stirred for 30 minutes at same temperature. The activated carbon was removed by filtration through hyflo bed and washed the hyflo bed with pre-heated mixture of acetone (100 ml) and purified water (100 ml). The resultant filtrate was cooled to 0-5°C and maintained for 90 min at the same temperature. The obtain solid was filtered at 0-5°C and washed with pre cooled mixture of acetone and purified water (1:1) to afford a pure crystalline Form A of Vonoprazan fumarate (1:1).
Yield: 80% (80 gm)
Purity: 99.82%.

Example-2:
Vonoprazan fumarate (5 g) was added to a mixture of acetone (40 ml) and water (40 ml) at 25-30°C and heated to 50-55°C to get homogenous solution, then added activated carbon (0.25 g) and stirred for 30 minutes at same temperature. The Activated carbon was removed by filtration through hyflo bed and washed the hyflo bed with pre-heated mixture of acetone (5 ml) and purified water (5 ml). The resultant filtrate was cooled to 0-5°C and maintained for 90 min at the same temperature. The obtain solid was filtered at 0-5°C and washed with pre cooled mixture of acetone and purified water (1:1) to afford a pure crystalline Form A of Vonoprazan fumarate (1:1).
Yield: 78% (3.9 gm)
Purity: 99.73%.

Example-3:
Vonoprazan fumarate (5 g) was added to a mixture of acetone (50 ml) and water (50 ml) at 25-30°C and heated to 50-55°C to get homogenous solution, then added activated carbon (0.25 g) and stirred for 30 minutes at same temperature. The Activated carbon was removed by filtration through hyflo bed and washed the hyflo bed with pre-heated mixture of acetone (5 ml) and purified water (5 ml). The resultant filtrate was cooled to 0-5°C and maintained for 90 min at the same temperature. The obtain solid was filtered at 0-5°C and washed with pre cooled mixture of acetone and purified water (1:1) to afford a pure crystalline Form A of Vonoprazan fumarate (1:1).
Yield: 76% (3.8 gm)
Purity: 99.68%.

Example-4:
Vonoprazan fumarate (5 g) was added to a mixture of acetone (30 ml) and water (50 ml) at 25-30°C and heated to 50-55°C to get homogenous solution, then added activated carbon (0.25 g) and stirred for 30 minutes at same temperature. The activated carbon was removed by filtration through hyflo bed and washed the hyflo bed with pre-heated mixture of acetone (5 ml) and purified water (5 ml). The resultant filtrate was cooled to 0-5°C and maintained for 90 min at the same temperature. The obtain solid was filtered at 0-5°C and washed with pre cooled mixture of acetone and purified water (1:1) to afford a pure crystalline Form A of Vonoprazan fumarate (1:1).
Yield: 76% (3.8 gm)
Purity: 99.79%.

Example-5:
Vonoprazan fumarate (5 g) was added to a mixture of acetone (40 ml) and water (60 ml) at 25-30°C and heated to 50-55°C to get homogenous solution, then added activated carbon (0.25 g) and stirred for 30 minutes at same temperature. The Activated carbon was removed by filtration through hyflo bed and washed the hyflo bed with pre-heated mixture of acetone (5 ml) and purified water (5 ml). The resultant filtrate was cooled to 0-5°C and maintained for 90 min at the same temperature. The obtain solid was filtered at 0-5°C and washed with pre cooled mixture of acetone and purified water (1:1) to afford a pure crystalline Form A of Vonoprazan fumarate (1:1).
Yield: 76% (3.8 gm)
Purity: 99.78%.
,CLAIMS:We claim:
1. A purification crystalline Form A of Vonoprazan Fumarate, comprising:
a. Crude Vonoprazan Fumarate was dissolved in mixture of acetone and water,
b. heating the obtained suspension at suitable temperature,
c. cooling the obtained solution in step b), and
d. isolating the pure crystalline Form A of Vonoprazan Fumarate.

2. The process as claimed in claim 1, wherein the suitable temperature is carried out at 40-75°C.

3. The process crystalline Form A of Vonoprazan Fumarate as claimed in claim 1, particle size distribution D90 less than 250 µm.

4. The process crystalline Form A of Vonoprazan Fumarate as claimed in claim 1, HPLC purity = 99.6%.