82586-55-8Relevant articles and documents
Physical characteristics and chemical degradation of amorphous quinapril hydrochloride
Guo, Yushen,Byrn, Stephen R.,Zografi, George
, p. 128 - 143 (2000)
This study was designed to investigate the relationships between the solid-state chemical instability and physical characteristics of a model drug, quinapril hydrochloride (QHCl), in the amorphous state. Amorphous QHCl samples were prepared by rapid evaporation from dichloromethane solution and by grinding and subsequent heating of the crystalline form. Physical characteristics, including the glass transition temperature and molecular mobility, were determined using differential scanning calorimetry, thermogravimetric analysis, powder x-ray diffractometry, polarizing microscopy, scanning electron microscopy, and infrared spectroscopy. The amorphous form of QHCl, produced by both methods, has a T(g) of 91°C. Isothermal degradation studies showed that cyclization of QHCl occurred at the same rate for amorphous samples prepared by the two methods. The activation energy was determined to be 30 to 35 kcal/mol. The rate of the reaction was shown to be affected by sample weight, dilution through mixing with another solid, and by altering the pressure above the sample. The temperature dependence for chemical reactivity below T(g) correlated very closely with the temperature dependence of molecular mobility. Above T(g), however, the reaction was considerably slower than predicted from molecular mobility. From an analysis of all data, it appears that agglomeration and sintering of particles caused by softening of the solid, particularly above T(g), and a resulting reduction of the particle surface/volume ratio play a major role in affecting the reaction rate by decreasing the rate of removal of the gaseous HCl product. (C) 2000 Wiley-Liss, Inc.
PROCESS FOR THE PREPARATION OF AMIDES OF N-[1-(S)-(ETHOXYCARBONYL)-3-PHENYLPROPYL]-L-ALANINE
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, (2015/01/07)
A process for the production of amides of N-[1-(S)-(ethoxycarbonyl)-3-phenylpropyl]-L-alanine is described. The process can be used for the production of key intermediates and finally the ACE inhibitors such as Ramipril, Enalapril, Quinapril, Trandolapril, Delapril and Moexipril starting from N-[1-(S)-(ethoxycarbonyl)-3-phenylpropyl]-L-alanine by the reaction with the appropriate amines.
CRYSTALLINE FORM OF QUINAPRIL HYDROCHLORIDE AND PROCESS FOR PREPARING THE SAME
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Page 25;13;16, (2008/06/13)
A novel crystalline form of quinapril hydrochloride of formula (I). An amorphous form of quinapril hydrochloride substantially free of impurities, specially diketopiperazine compound, and conforming to pharmacopoeial specifications formed from the said novel crystalline form of quinapril hydrochloride of formula (I). The crystalline quinapril hydrochloride is in the form nitroalkane solvate in which the nitroalkane is nitromethane, nitroethane and nitropropane. Each such nitroalkane solvate having particular characteristic X- ray diffraction patterns. A process for preparation of amorphous from of quinapril hydrochloride, substantially free of impurities, specially diketopiperazine compound, and conforming to pharmacopoeial specifications, using the novel crystalline quinapril hydrochloride as an intermediate. The process involves obtaining free base compound of formula (V) by adjusting the pH of a solution of the benzyl ester maleate salt of quinapril of formula (V) between 7.5-8.5 in a mixture of water and an organic solvent; catalytic hydrogenation of this compound (V) in an alcoholic solvent in the presence of concentrated hydrochloric acid or hydrogen chloride dissolved in an alcoholic solvent and in the presence of catalytic amounts of Pd/C to obtain a residue containing formula (I); crystallization of the said residue by evaporating the alcoholic solvent from a nitroalkane solvent to give crystalline quinapril hydrochloride, associated with a solvate of the nitroalkane solvent, and drying the crystalline quinapril hydrochloride nitroalkane solvate at a temperature between 40°C and 45°C under vacuum to give amorphous quinapril hydrochloride of formula (I).
