Crystalline compounds

1. A pharmaceutical composition, wherein the pharmaceutical composition comprises 100 mg to 500 mg of Crystalline Form A of (1R,5S)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane hydrochloride and a pharmaceutically acceptable diluent or carrier, wherein the Crystalline Form A exhibits an X-ray powder diffraction (XRPD) pattern comprising d-spacing (Å) values of 5.7, 5.4, 5.2, 4.8, 4.6, 4.3, 3.9, and 3.5.

2. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition comprises 100 mg to 400 mg of Crystalline Form A.

3. The pharmaceutical composition of claim 2 , wherein the Crystalline Form A exhibits an X-ray powder diffraction (XRPD) pattern comprising d-spacing (Å) values of 7.2, 6.4, 5.7, 5.4, 5.2, 4.9, 4.8, 4.6, 4.3, 3.9, and 3.5.

4. The pharmaceutical composition of claim 2 , wherein the Crystalline Form A exhibits an X-ray powder diffraction (XRPD) pattern comprising d-spacing (Å) values of 12.9, 7.2, 6.4, 6.1, 5.7, 5.4, 5.2, 4.9, 4.8, 4.6, 4.4, 4.3, 4.2, 4.1, 3.9, 3.6, 3.5, 3.4, and 3.2.

5. The pharmaceutical composition of claim 1 , wherein the Crystalline Form A exhibits an X-ray powder diffraction (XRPD) pattern comprising 2-theta (°) values of 12.3, 13.8, 15.4, 16.6, 17.2, 18.2, 18.5, 19.5, 20.5, 20.7, 22.9, and 25.7, wherein the XRPD is measured using an incident beam of Cu Kα radiation of wavelength 1.54059 Å.

6. The pharmaceutical composition of claim 1 , wherein the Crystalline Form A exhibits an X-ray powder diffraction (XRPD) pattern comprising 2-theta (°) values of 6.9, 12.3, 13.8, 14.5, 15.4, 16.6, 17.2, 18.2, 18.5, 19.5, 20.1, 20.5, 20.7, 21.0, 21.5, 22.9, 24.7, 25.2, 25.4, 25.7, 26.4, 27.5, and 27.8, wherein the XRPD is measured using an incident beam of Cu Kα radiation of wavelength 1.54059 Å.

7. The pharmaceutical composition of claim 2 , wherein the Crystalline Form A exhibits an X-ray powder diffraction (XRPD) pattern measured using an incident beam of Cu Kα radiation of wavelength 1.54059 Å comprising five peaks selected from those shown in FIG. 1 .

8. The pharmaceutical composition of claim 2 , wherein the Crystalline Form A exhibits an X-ray powder diffraction (XRPD) pattern measured using an incident beam of Cu Kα radiation of wavelength 1.54059 Å comprising nine peaks selected from those shown in FIG. 1 .

9. The pharmaceutical composition of claim 2 , wherein the Crystalline Form A exhibits an X-ray powder diffraction (XRPD) pattern measured using an incident beam of Cu Kα radiation of wavelength 1.54059 Å substantially as shown in FIG. 1 .

10. The pharmaceutical composition of claim 1 , wherein the Crystalline Form A exhibits an X-ray powder diffraction (XRPD) pattern comprising d-spacing (Å) values selected from Table A, B, and C below:

TABLE A

°2θ

d space (Å)

Intensity (%)

15.42 ± 0.20

5.741 ± 0.074

26

16.55 ± 0.20

5.352 ± 0.064

40

17.15 ± 0.20

5.167 ± 0.060

29

18.50 ± 0.20

4.792 ± 0.051

100

19.45 ± 0.20

4.560 ± 0.046

38

20.46 ± 0.20

4.338 ± 0.042

43

20.68 ± 0.20

4.291 ± 0.041

80

22.90 ± 0.20

3.880 ± 0.033

22

25.69 ± 0.20

3.466 ± 0.027

70

TABLE B

°2θ

d space (Å)

Intensity (%)

12.26 ± 0.20

7.211 ± 0.117

22

13.78 ± 0.20

6.421 ± 0.093

36

15.42 ± 0.20

5.741 ± 0.074

26

16.55 ± 0.20

5.352 ± 0.064

40

17.15 ± 0.20

5.167 ± 0.060

29

18.19 ± 0.20

4.873 ± 0.053

100

18.50 ± 0.20

4.792 ± 0.051

100

19.45 ± 0.20

4.560 ± 0.046

38

20.46 ± 0.20

4.338 ± 0.042

43

20.68 ± 0.20

4.291 ± 0.041

80

22.90 ± 0.20

3.880 ± 0.033

22

25.69 ± 0.20

3.466 ± 0.027

70

TABLE C

°2θ

d space (Å)

Intensity (%)

 6.87 ± 0.20

12.859 ± 0.374 

6

12.26 ± 0.20

7.211 ± 0.117

22

13.78 ± 0.20

6.421 ± 0.093

36

14.49 ± 0.20

6.106 ± 0.084

6

15.42 ± 0.20

5.741 ± 0.074

26

16.55 ± 0.20

5.352 ± 0.064

40

17.15 ± 0.20

5.167 ± 0.060

29

18.19 ± 0.20

4.873 ± 0.053

100

18.50 ± 0.20

4.792 ± 0.051

100

19.45 ± 0.20

4.560 ± 0.046

38

20.06 ± 0.20

4.422 ± 0.044

9

20.46 ± 0.20

4.338 ± 0.042

43

20.68 ± 0.20

4.291 ± 0.041

80

20.96 ± 0.20

4.236 ± 0.040

11

21.54 ± 0.20

4.123 ± 0.038

10

22.90 ± 0.20

3.880 ± 0.033

22

24.69 ± 0.20

3.602 ± 0.029

3

25.17 ± 0.20

3.535 ± 0.028

14

25.44 ± 0.20

3.499 ± 0.027

13

25.69 ± 0.20

3.466 ± 0.027

70

26.36 ± 0.20

3.378 ± 0.025

13

27.52 ± 0.20

3.239 ± 0.023

23

27.76 ± 0.20

3.211 ± 0.023

7.

11. The pharmaceutical composition of claim 2 , wherein the Crystalline Form A exhibits an X-ray powder diffraction (XRPD) pattern measured using an incident beam of Cu Kα radiation of wavelength 1.54059 Å comprising five peaks selected from those shown in FIG. 35 , FIG. 37 , or FIG. 47 .

12. The pharmaceutical composition of claim 2 , wherein the Crystalline Form A exhibits an X-ray powder diffraction (XRPD) pattern measured using an incident beam of Cu Kα radiation of wavelength 1.54059 Å comprising nine peaks selected from those shown in FIG. 35 , FIG. 37 , or FIG. 47 .

13. The pharmaceutical composition of claim 2 , wherein the Crystalline Form A exhibits an X-ray powder diffraction (XRPD) pattern measured using an incident beam of Cu Kα radiation of wavelength 1.54059 Å substantially as shown in FIG. 35 , FIG. 37 , or FIG. 47 .

14. A pharmaceutical composition, wherein the pharmaceutical composition comprises 100 mg to 500 mg of Crystalline Form B of (1R,5S)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane hydrochloride and a pharmaceutically acceptable diluent or carrier, wherein the Crystalline Form B exhibits an X-ray powder diffraction (XRPD) pattern comprising d-spacing (Å) values of 14.6, 5.1, 4.7, 4.6, and 3.6.

15. The pharmaceutical composition of claim 14 , wherein the pharmaceutical composition comprises 100 mg to 400 mg of Crystalline Form B.

16. The pharmaceutical composition of claim 15 , wherein the Crystalline Form B exhibits an X-ray powder diffraction (XRPD) pattern comprising d-spacing (Å) values of 14.6, 6.7, 5.1, 4.7, 4.6, 3.8, 3.7, 3.6, and 3.2.

17. The pharmaceutical composition of claim 15 , wherein the Crystalline Form B exhibits an X-ray powder diffraction (XRPD) pattern comprising d-spacing (Å) values of 14.6, 7.3, 6.7, 6.0, 5.9, 5.5, 5.2, 5.1, 4.9, 4.7, 4.6, 4.5, 4.2, 4.1, 3.9, 3.8, 3.7, 3.6, 3.5, 3.4, 3.3, 3.2, 3.1, and 3.0.

18. The pharmaceutical composition of claim 15 , wherein the Crystalline Form B exhibits an X-ray powder diffraction (XRPD) pattern comprising d-spacing (Å) values selected from Table D, E, and F below:

TABLE D

°2θ

d space (Å)

Intensity (%)

 6.04 ± 0.20

14.620 ± 0.484 

13

17.41 ± 0.20

5.089 ± 0.058

14

18.94 ± 0.20

4.681 ± 0.049

79

19.19 ± 0.20

4.622 ± 0.048

100

24.39 ± 0.20

3.646 ± 0.029

23

TABLE E

°2θ

d space (Å)

Intensity (%)

 6.04 ± 0.20

14.620 ± 0.484 

13

13.21 ± 0.20

6.699 ± 0.101

21

17.41 ± 0.20

5.089 ± 0.058

14

18.94 ± 0.20

4.681 ± 0.049

79

19.19 ± 0.20

4.622 ± 0.048

100

23.59 ± 0.20

3.769 ± 0.032

16

23.79 ± 0.20

3.737 ± 0.031

43

24.39 ± 0.20

3.646 ± 0.029

23

28.15 ± 0.20

3.168 ± 0.022

24

TABLE F

°2θ

d space (Å)

Intensity (%)

 6.04 ± 0.20

14.620 ± 0.484 

13

12.12 ± 0.20

7.296 ± 0.120

6

13.21 ± 0.20

6.699 ± 0.101

21

14.86 ± 0.20

5.958 ± 0.080

8

15.13 ± 0.20

5.853 ± 0.077

5

16.02 ± 0.20

5.529 ± 0.069

1

16.90 ± 0.20

5.242 ± 0.062

4

17.41 ± 0.20

5.089 ± 0.058

14

18.23 ± 0.20

4.861 ± 0.053

10

18.94 ± 0.20

4.681 ± 0.049

79

19.19 ± 0.20

4.622 ± 0.048

100

19.91 ± 0.20

4.457 ± 0.044

4

21.05 ± 0.20

4.217 ± 0.040

11

21.27 ± 0.20

4.173 ± 0.039

2

21.74 ± 0.20

4.085 ± 0.037

4

22.55 ± 0.20

3.939 ± 0.034

6

23.59 ± 0.20

3.769 ± 0.032

16

23.79 ± 0.20

3.737 ± 0.031

43

24.39 ± 0.20

3.646 ± 0.029

23

25.34 ± 0.20

3.512 ± 0.027

1

26.06 ± 0.20

3.416 ± 0.026

2

26.61 ± 0.20

3.347 ± 0.025

1

27.15 ± 0.20

3.282 ± 0.024

2

28.15 ± 0.20

3.168 ± 0.022

24

28.66 ± 0.20

3.112 ± 0.021

13

29.47 ± 0.20

3.028 ± 0.020

13.

19. The pharmaceutical composition of claim 15 , wherein the Crystalline Form B exhibits an X-ray powder diffraction (XRPD) pattern measured using an incident beam of Cu Kα radiation of wavelength 1.54059 Å comprising five peaks selected from those shown in FIG. 40 or FIG. 48 .

20. The pharmaceutical composition of claim 15 , wherein the Crystalline Form B exhibits an X-ray powder diffraction (XRPD) pattern measured using an incident beam of Cu Kα radiation of wavelength 1.54059 Å substantially as shown in FIG. 40 or FIG. 48 .

21. A method for treatment of attention deficit hyperactivity disorder in a patient in need thereof, wherein the method comprises administering to the patient a therapeutically effective amount of a pharmaceutical composition, wherein the pharmaceutical composition comprises 100 mg to 500 mg of Crystalline Form A of (1R,5S)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane hydrochloride and a pharmaceutically acceptable diluent or carrier, wherein the Crystalline Form A exhibits an X-ray powder diffraction (XRPD) pattern comprising d-spacing (Å) values of 5.7, 5.4, 5.2, 4.8, 4.6, 4.3, 3.9, and 3.5.

22. The method of claim 21 , wherein the pharmaceutical composition comprises 100 mg to 400 mg of Crystalline Form A.

23. The method of claim 22 , wherein the attention deficit hyperactivity disorder is co-morbid with depression, substance abuse, or anxiety.

24. The method of claim 23 , wherein the attention deficit hyperactivity disorder is co-morbid with substance abuse.

25. A method for treatment of attention deficit hyperactivity disorder in a patient in need thereof, wherein the method comprises administering to the patient a therapeutically effective amount of a pharmaceutical composition, wherein the pharmaceutical composition comprises 100 mg to 500 mg of Crystalline Form B of (1R,5S)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane hydrochloride and a pharmaceutically acceptable diluent or carrier, wherein the Crystalline Form B exhibits an X-ray powder diffraction (XRPD) pattern comprising d-spacing (Å) values of 14.6, 5.1, 4.7, 4.6, and 3.6.

26. The method of claim 25 , wherein the pharmaceutical composition comprises 100 mg to 400 mg of Crystalline Form B.

27. The method of claim 26 , wherein the attention deficit hyperactivity disorder is co-morbid with depression, substance abuse, or anxiety.

28. The method of claim 27 , wherein the attention deficit hyperactivity disorder is co-morbid with substance abuse.

29. The pharmaceutical composition of claim 1 , wherein the Crystalline Form A comprises less than 5 wt. % of any other crystalline form of (1R,5S)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane hydrochloride.

30. The pharmaceutical composition of claim 1 , wherein the Crystalline Form A comprises less than 1 wt. % of any other crystalline form of (1R,5S)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane hydrochloride.

31. The pharmaceutical composition of claim 4 , wherein the Crystalline Form A comprises less than 5 wt. % of any other crystalline form of (1R,5S)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane hydrochloride.

32. The pharmaceutical composition of claim 4 , wherein the Crystalline Form A comprises less than 1 wt. % of any other crystalline form of (1R,5S)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane hydrochloride.

33. The pharmaceutical composition of claim 5 , wherein the Crystalline Form A comprises less than 5 wt. % of any other crystalline form of (1R,5S)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane hydrochloride.

34. The pharmaceutical composition of claim 5 , wherein the Crystalline Form A comprises less than 1 wt. % of any other crystalline form of (1R,5S)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane hydrochloride.

35. The pharmaceutical composition of claim 14 , wherein the Crystalline Form B comprises less than 5 wt. % of any other crystalline form of (1R,5S)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane hydrochloride.

36. The pharmaceutical composition of claim 14 , wherein the Crystalline Form B comprises less than 1 wt. % of any other crystalline form of (1R,5S)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane hydrochloride.

37. The method of claim 21 , wherein the Crystalline Form A comprises less than 5 wt. % of any other crystalline form of (1R,5S)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane hydrochloride.

38. The method of claim 21 , wherein the Crystalline Form A comprises less than 1 wt. % of any other crystalline form of (1R,5S)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane hydrochloride.

39. The method of claim 25 , wherein the Crystalline Form B comprises less than 5 wt. % of any other crystalline form of (1R,5S)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane hydrochloride.

40. The method of claim 25 , wherein the Crystalline Form B comprises less than 1 wt. % of any other crystalline form of (1R,5S)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane hydrochloride.