Crystalline form of a biphenyl compound
The invention provides a crystalline 1,2-ethanedisulfonic acid salt of biphenyl-2-ylcarbamic acid 1-[2-(2-chloro-4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-5-methoxyphenylcarbamoyl)ethyl]piperidin-4-yl ester or a solvate thereof. This invention also provides pharmaceutical compositions comprising such a salt or prepared using such a salt; processes and intermediates for preparing such a salt; and methods of using such a salt to treat a pulmonary disorder.
1. A crystalline 1,2-ethanedisulfonic acid salt of biphenyl-2-ylcarbamic acid 1-[2-(2-chloro-4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-5-methoxyphenylcarbamoyl)ethyl]piperidin-4-yl ester.
2. The compound of claim 1 , wherein the compound is characterized by a differential scanning calorimetry trace which shows a maximum endothermic heat flow in the range of about 215° C. to about 240° C.
3. The compound of claim 1 , wherein the compound is characterized by a differential scanning calorimetry trace which shows a maximum endothermic heat flow in the range of about 215° C. to about 229° C.
4. The compound of claim 1 , wherein the compound is characterized by a differential scanning calorimetry trace which shows a maximum endothermic heat flow in the range of about 230° C. to about 240° C.
5. The compound of claim 1 , wherein the compound is characterized by an differential scanning calorimetry trace which is substantially in accordance with that shown in FIG. 1 in the temperature range above 200° C.
6. The compound of claim 1 , wherein the compound is characterized by an differential scanning calorimetry trace which is substantially in accordance with that shown in FIG. 2 in the temperature range above 200° C.
7. The compound of claim 1 , wherein the compound is characterized by a powder x-ray diffraction pattern having diffraction peaks at 2θ values of 5.0±0.3 and 15.0±0.3.
8. The compound of claim 1 , wherein the compound 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. 3 .
9. The compound of claim 1 , wherein the compound 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. 4 .
10. The compound of claim 1 , wherein the compound has infrared absorption spectrum with significant absorption bands at about 704, 748, 768, 841, 900, 1055, 1104, 1166, 1218, 1294, 1408, 1522, 1609, 1655, and 1701 cm −1 .
11. The compound of claim 1 , wherein the compound is characterized by an infrared absorption spectrum substantially in accordance with that shown in FIG. 5 .
12. The compound of claim 1 , in micronized form.