New crystal form of prasugrel and preparation method thereof

Abstract

The invention discloses a new crystal form of prasugrel, and also discloses a preparation method thereof. The invention solves the problem that prasugrel is unfavorable for making medicines. The invention has the beneficial effects of providing multiple new prasugrel crystal forms, which have the advantages of good stability, good dissolution rate after being prepared as a medicine, and the like.

Description

technical field

[0001] The invention belongs to the field of medicine and chemical industry, and in particular relates to a new crystal form of an antithrombotic drug prasugrel and a preparation method thereof. Background technique

[0002] The chemical name of prasugrel is 2-acetoxy-5-(a-cyclopropylcarbonyl-2-fluorobenzyl)-4,5,6,7-tetrahydrothieno[3,2-c ] pyridine, the structural formula is as shown in formula I. Prasugrel is an oral antiplatelet drug jointly developed by Eli Lilly and its partner Daiichi Pharmaceutical Sankyo,

[0003]

[0004] Formula I.

[0005] Prasugrel, an adenosine diphosphate (ADP) receptor antagonist, is a prodrug that is effectively converted in vivo to its active metabolite R-138727. R-138727 reduces the dependence on cytochrome P-450 enzymes, and rapidly, specifically, and irreversibly binds to the purine base receptor of platelet P2Y12, inhibits the activity and aggregation of platelets regulated by ADP, and thus plays an anti-platelet ef...

Examples

Embodiment 1

[0055] Example 1 Preparation of prasugrel M crystal form

[0056] Add 2 grams of prasugrel crude product into 6ml 1,4-dioxane, heat to 30 degrees to dissolve, slowly cool down to room temperature under stirring condition, a white solid precipitates, continue to stir for 2 hours, filter to obtain white crystals, Vacuum dried to obtain 1.71 g of the product, with a yield of 85.5%.

Embodiment 2

[0057] Example 2 Preparation of prasugrel M crystal form

[0058] Add 2 grams of prasugrel crude product into 6ml tetrahydrofuran, heat to 30 degrees to dissolve, slowly cool down to room temperature under stirring condition, a white solid precipitates out, continue to stir for 0.5 hours, filter to obtain white crystals, and vacuum dry to obtain the product 1.58 grams, yield 79.0%.

Embodiment 3

[0059] Example 3 Preparation of prasugrel N crystal form

[0060] Add 2 grams of prasugrel crude product to 10ml of a mixed solvent of methyl ethyl ketone:petroleum ether=1:2, heat to 80 degrees to dissolve, let it stand and slowly cool down to room temperature, a white solid precipitates, grow crystals for 2 hours, filter to obtain White crystals were vacuum-dried to obtain 1.66 g of the product, with a yield of 83.1%.

technical field

[0001] The invention belongs to the field of medicine and chemical industry, and in particular relates to a new crystal form of an antithrombotic drug prasugrel and a preparation method thereof. Background technique

[0002] The chemical name of prasugrel is 2-acetoxy-5-(a-cyclopropylcarbonyl-2-fluorobenzyl)-4,5,6,7-tetrahydrothieno[3,2-c ] pyridine, the structural formula is as shown in formula I. Prasugrel is an oral antiplatelet drug jointly developed by Eli Lilly and its partner Daiichi Pharmaceutical Sankyo,

[0003]

[0004] Formula I.

[0005] Prasugrel, an adenosine diphosphate (ADP) receptor antagonist, is a prodrug that is effectively converted in vivo to its active metabolite R-138727. R-138727 reduces the dependence on cytochrome P-450 enzymes, and rapidly, specifically, and irreversibly binds to the purine base receptor of platelet P2Y12, inhibits the activity and aggregation of platelets regulated by ADP, and thus plays an anti-platelet ef...

Examples

Embodiment 1

[0055] Example 1 Preparation of prasugrel M crystal form

[0056] Add 2 grams of prasugrel crude product into 6ml 1,4-dioxane, heat to 30 degrees to dissolve, slowly cool down to room temperature under stirring condition, a white solid precipitates, continue to stir for 2 hours, filter to obtain white crystals, Vacuum dried to obtain 1.71 g of the product, with a yield of 85.5%.

Embodiment 2

[0057] Example 2 Preparation of prasugrel M crystal form

[0058] Add 2 grams of prasugrel crude product into 6ml tetrahydrofuran, heat to 30 degrees to dissolve, slowly cool down to room temperature under stirring condition, a white solid precipitates out, continue to stir for 0.5 hours, filter to obtain white crystals, and vacuum dry to obtain the product 1.58 grams, yield 79.0%.

Embodiment 3

[0059] Example 3 Preparation of prasugrel N crystal form

[0060] Add 2 grams of prasugrel crude product to 10ml of a mixed solvent of methyl ethyl ketone:petroleum ether=1:2, heat to 80 degrees to dissolve, let it stand and slowly cool down to room temperature, a white solid precipitates, grow crystals for 2 hours, filter to obtain White crystals were vacuum-dried to obtain 1.66 g of the product, with a yield of 83.1%.

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