Telaprevir intermediate in B crystal form and synthesis method thereof

Abstract

The invention relates to a telaprevir intermediate (2S)-2-cyclohexyl-N-(2-pyrazinyl carbonyl)-glycyl-3-methyl-L-valine in a B crystal form, and a synthesis method thereof, and belongs to the technical field of drug synthesis. The telaprevir intermediate in the B crystal form is subjected to Cu-Ka radiation by adopting X-ray powder diffraction at the angle of 2 times of Theta, characteristic peaks appear at the points of 5.5+ / -0.2, 7.4+ / -0.2, 10.7+ / -0.2, 16.7+ / -0.2, 17.4+ / -0.2, 17.6+ / -0.2, 18.4+ / -0.2, 19.2+ / -0.2, 20.5+ / -0.2, 21.5+ / -0.2, and 22.1+ / -0.2; the solid is white, the melting point is 221.6-229.3 DEG C, the moisture content is 0.1-0.5 percent, and the residue solvent is 8-12 percent. The invention further discloses the synthesis method for the telaprevir intermediate in the B crystal form. The telaprevir intermediate in the B crystal form is good in appearance, small in moisture content, high in temperature and humidity stability, and high in purity.

Description

technical field [0001] The present invention relates to a telaprevir intermediate and a synthesis method thereof, in particular to a telaprevir intermediate (2S)-2-cyclohexyl-N-(2-pyrazinylcarbonyl)glycyl-3 -Methyl-L-valine B crystal form and a synthesis method thereof, belonging to the technical field of pharmaceutical synthesis. Background technique [0002] Telaprevir (TVR), chemical name: (1S,3aR,6aS)-(2S)-2-cyclohexyl-N-(carbonylpyrazine)-glycyl-3-methyl-L-valyl -N-(1S)-1-[(cyclopropylamino)-oxoacetyl]butyl-octahydrocyclopenta[c]pyrrole-1-carboxamide, CAS registration number: 402957-28-2, is a A drug that inhibits HCV genotype 1 NS3 / 4A serine protease and can terminate HCV replication. Acts as a protease inhibitor by binding to the virus and preventing its proliferation. The structural formula of telaprevir is as follows: [0003] [0004] In May 2011, the U.S. FDA approved the listing of telaprevir from Vertex Pharmaceuticals, whose trade name is Incivek, for ad...

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Problems solved by technology

[0015] Although the above-mentioned three synthetic methods finally synthesized the telaprevir intermediate (2S)-2-cyclohexyl-N-(2-pyrazinylcarbonyl) glycyl-3-methyl-L-valine , but the synthesized telaprevir intermediates are all white solids (white solid), the purity is not high, and the crystal form and other physical properties of the intermediates are not described in the above three documents, and these are all May affect the potency of the final product

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