Crystalline forms of a dimethylphenyl compound

Abstract

The invention relates to crystalline free base forms of biphenyl-2-ylcarbamic acid 1-[2-(4-{[(R)-2-(3-formylamino-4-hydroxyphenyl)-2-hydroxyethylamino]methyl}-2,5-dimethylphenylcarbamoyl)ethyl]piperidin-4-yl ester or a solvate thereof. This invention also relates to pharmaceutical compositions containing or prepared from such crystalline forms; processes and intermediates useful for preparing such crystalline forms; and methods of using such crystalline forms to, for example, treat a pulmonary disorder.

1 - 22 . (canceled) 
     
     
         23 . A method of treating chronic obstructive pulmonary disease or asthma, the method comprising administering to a patient a therapeutically effective amount of a crystalline free base form of biphenyl-2-ylcarbamic acid 1-[2-(4-{[(R)-2-(3-formylamino-4-hydroxyphenyl)-2-hydroxyethylamino]methyl}-2,5-dimethylphenylcarbamoyl)ethyl]piperidin-4-yl ester selected from:
 (a) Form I characterized by a powder x-ray diffraction pattern having diffraction peaks at 2θ values of about 17.7±0.3, 18.2±0.3, 21.7±0.3 and 23.2±0.3;   (b) Form II characterized by a powder x-ray diffraction pattern having diffraction peaks at 2θ values of about 20.7±0.3, 21.6±0.3, 22.5±0.3 and 23.2±0.3; and   (c) Form III characterized by a powder x-ray diffraction pattern having diffraction peaks at 2θ values of about 15.5±0.3, 18.1±0.3, 19.2±0.3 and 21.8±0.3.   
     
     
         24 . A method of producing bronchodilation in a mammal, the method comprising administering to a mammal a bronchodilation-producing amount of a crystalline free base form of biphenyl-2-ylcarbamic acid 1-[2-(4-{[(R)-2-(3-formylamino-4-hydroxyphenyl)-2-hydroxyethylamino]methyl}-2,5-dimethylphenylcarbamoyl)ethyl]piperidin-4-yl ester selected from:
 (a) Form I characterized by a powder x-ray diffraction pattern having diffraction peaks at 2θ values of about 17.7±0.3, 18.2±0.3, 21.7±0.3 and 23.2±0.3;   (b) Form II characterized by a powder x-ray diffraction pattern having diffraction peaks at 2θ values of about 20.7±0.3, 21.6±0.3, 22.5±0.3 and 23.2±0.3; and   (c) Form III characterized by a powder x-ray diffraction pattern having diffraction peaks at 2θ values of about 15.5±0.3, 18.1±0.3, 19.2±0.3 and 21.8±0.3.   
     
     
         25 - 27 . (canceled) 
     
     
         28 . The method of  claim 23  or  24 , wherein the crystalline free base form is characterized by a powder x-ray diffraction pattern in which the peak positions are substantially in accordance with the peak positions of the pattern shown in  FIG. 1 ,  FIG. 2  or  FIG. 3 . 
     
     
         29 . The method of  claim 23  or  24 , wherein the crystalline free base form is characterized by a differential scanning calorimetry trace which is substantially in accordance with that shown in  FIG. 4 ,  FIG. 5  or  FIG. 6 .