FIELD: chemistry.
SUBSTANCE: invention relates to a novel crystalline modification of crystalline β-modification of N-(3-ethylphenyl)-6,7-bis(2-methoxyethoxy)quinazoline-4-amine hydrochloride (erlotinib hydrochloride). Said compound has properties of inhibitor of epidermal growth factor of tyrosine kinase receptors and can be used for treating oncological diseases. Crystalline β-modification is characterised by a set of interplanar distances (d, Å) and corresponding intensities (Irelative,%) – 22.849–27.01 %; 21.101 – 33.82 %; 19.175 – 0.41 %; 18.609 – 48.34 %; 16.707 - 100 %; 14.463 – 15.57 %; 12.358 -13.54 %; 10.869 – 11.52 %; 10.099 – 14.19 %; 9.372 – 29.03 %; 8.759 -14.52 %; 7.160 – 14.19 %; 6.958 – 12.17 %; 6.557 – 11.19 %; 6.252 – 10.46 %; 6.007 – 13.54 %; 5.865 – 14.19 %; 5.721 – 13.22 %; 5.564 – 15.25 %; 5.337 -17.60 %; 5.206 – 15.25 %; 4.925 – 14.52 %; 4.742 – 18.90 %; 4.591 – 16.87 %; 4.397 – 16.55 %; 4.300 – 19.63 %; 4.187 – 20.60 %; 3.958 – 22.95 %; 3.914 -23.36 %; 3.821 – 31.79 %; 3.717 – 29.03 %; 3.528 – 19.95 %; 3.444 – 19.63 %; 3.325 – 12.73 %; 3.215 – 10.79 %; 3.053 – 10.46 %; 2.889 – 11.19 %; 2.837 -10.79 %; 2.721 – 7.79 %; 2.607 – 5.76 %; 2.497 – 5.43 %; 2.341 – 6.08 %; 2.274 – 5.43 % and melting temperature equal to 212.4 ± 0.5 °C. Invention also relates to a method of producing said crystalline β-modification. Method comprises dissolving erlotinib hydrochloride at 40–100 °C in distilled water, acidified with 0.1 M hydrochloric acid to pH 2–4, frozen at cooling rate not less than 60 deg/min and subjected to sublimation drying.
EFFECT: sublimation drying of frozen erlotinib hydrochloride solution is carried out at temperatures: on condenser (-43)–(-56) °C; on product (-196)–(+50) °C and residual pressure in chamber (9-3)×10-2 torr for 22–26 hours.
4 cl, 5 dwg, 4 tbl, 4 ex
