SOLID FORMS OF TERT-BUTYL (S)-2((2S,3R)-1-AMINO-3-HYDROXY-1-OXOBU TAN-2-YL)-1-OXO-2, 5-DIAZASPIRO [3.4] OCTAN E-5-CARBOXYLATE AND METHODS OF PREPARING THEM

1 . A method of preparing the solid crystalline Form I of compound A:

the method comprising:

dissolving compound A in ethyl acetate and heating the solution;

cooling the solution; and

adding a diisopropyl ether to the solution.

2 . The method of claim 1 , wherein the solution is heated to between about 65° C. and about 70° C.

3 . The method of claim 1 , wherein the solution is cooled to about 25° C.

4 . The method of any one of claims 1 to 3 , wherein the solid crystalline Form I of compound A has peaks (2θ) chosen from those having about the following values: 6.9, 8.4, 10.3, and 12.8 in a powder X-ray diffraction pattern.

5 . The method of claim 4 , wherein the solid crystalline Form I of compound A further has one or more peaks (2θ) chosen from those having about the following values: 13.7, 15.3, 15.7, 16.8, 17.3, 18.5, and 19.9 in a powder X-ray diffraction pattern.

6 . The of the method of any one of claims 1 to 3 , wherein the solid crystalline Form I of compound A has peaks (2θ) chosen from those having about the following values: 6.9, 8.4, 10.3, 12.8, and 13.7 in a powder X-ray diffraction pattern.

7 . The method on any one of claims 1 to 3 , wherein the solid crystalline Form I of compound A has peaks (2θ) chosen from those having about the following values 6.9, 8.4, 10.3, 12.8, 13.7, 15.3, and 15.7 in a powder X-ray diffraction pattern.

8 . The method of any one of claims 1 to 3 , having peaks (2θ) chosen from those having about the following values 6.9, 8.4, 10.3, 12.8, 13.7, 15.3, 15.7, and 16.8 in a powder X-ray diffraction pattern.

9 . The method of any one of claims 1 to 3 , wherein the solid crystalline Form I of compound A has peaks (2θ) chosen from those having about the following values 6.9, 8.4, 10.3, 12.8, 13.7, 15.3, 15.7, 16.8, and 17.3 in a powder X-ray diffraction pattern.

10 . The method of any one of claims 1 to 3 , wherein the solid crystalline Form I of compound A has peaks (2θ) chosen from those having about the following values 6.9, 8.4, 10.3, 12.8, 13.7, 15.3, 15.7, 16.8, 17.3, and 18.5 in a powder X-ray diffraction pattern.

11 . The method of any one of claims 1 to 3 , wherein the solid crystalline Form I of compound A has 3, 4 or 5 peaks (2θ) chosen from those having about the following values 6.9, 8.4, 10.3, 12.8, 13.7, 15.3, 15.7, 16.8, 17.3, 18.5, and 19.9 in a powder X-ray diffraction patterns.

12 . The method of any one of claims 1 to 3 , wherein the solid crystalline Form I of compound A has an XRPD pattern substantially similar to one of the XRPD patterns shown in FIG. 1 .

13 . The method of any one of claims 1 to 12 , wherein the solid crystalline Form I of compound A has a DSC with endothermic peaks at about 159° C.

14 . A solid crystalline form of Compound A:

wherein the solid crystalline form is crystalline Form II of Compound A.

15 . The solid crystalline form of claim 14 , having peaks (2θ) chosen from those having about the following values: 9.4, 10.8, 11.9, and 13.0 in a powder X-ray diffraction patterns.

16 . The solid crystalline form of claim 15 , further having one or more peaks (2θ) chosen from those having about the following values: 13.7, 15.5, 16.0, 20.0, 20.4, 21.3 and 23.3 in a powder X-ray diffraction pattern.

17 . The solid crystalline form of claim 14 , having peaks (2θ) chosen from those having about the following values: 9.4, 10.8, 11.9, 13.0, and 13.7 in a powder X-ray diffraction pattern.

18 . The solid crystalline form of claim 14 , having peaks (2θ) chosen from those having about the following values 9.4, 10.8, 11.9, 13.0, 13.7, 15.5, and 16.0 in a powder X-ray diffraction pattern.

19 . The solid crystalline form of claim 14 , having peaks (2θ) chosen from those having about the following values 9.4, 10.8, 11.9, 13.0, 13.7, 15.5, 16.0, 20.0, and 20.4 in a powder X-ray diffraction pattern.

20 . The solid crystalline form of claim 14 , having peaks (2θ) chosen from those having about the following values 9.4, 10.8, 11.9, 13.0, 13.7, 15.5, 16.0, 20.0, 20.4, and 21.3 in a powder X-ray diffraction pattern.

21 . The solid crystalline form of claim 14 , having peaks (2θ) chosen from those having about the following values 9.4, 10.8, 11.9, 13.0, 13.7, 15.5, 16.0, 20.0, 20.4, 21.3 and 23.3 in a powder X-ray diffraction pattern.

22 . The solid crystalline form of claim 14 , having 3, 4 or 5 peaks (2θ) chosen from those having about the following values 9.4, 10.8, 11.9, 13.0, 13.7, 15.5, 16.0, 20.0, 20.4, 21.3 and 23.3 in a powder X-ray diffraction pattern.

23 . The solid crystalline form of claim 14 , having an XRPD pattern substantially similar to one of the two XRPD patterns shown in FIG. 3 .

24 . The solid crystalline form of any one of claims 14 to 23 , having a DSC with endothermic peaks at about 82° C. and at about 159° C.

25 . The solid crystalline form of any one of claims 14 to 24 , having a TGA showing dehydration approximately at above 60° C., with a loss of water of approximately 9.6% by weight.

26 . The solid crystalline form of any one of claims 14 to 25 , having a DVS showing about 11% change in mass at 0% RH and 25° C. and the mass does not lose water at or above 20% RH.

27 . A solid composition comprising the solid crystalline form of any one of claims 14 to 26 , wherein the solid composition is at least 99%, at least 95%, at least 90%, at least 80%, at least 70%, at least 60%, or at least 50%, by weight, free of any other solid forms of Compound A.

28 . A pharmaceutical composition comprising the solid crystalline form of any one of claims 14 to 26 and a pharmaceutically acceptable excipient.

29 . The pharmaceutical composition of claim 28 , wherein the solid crystalline form is at least 99%, at least 95%, at least 90%, at least 80%, at least 70%, at least 60%, or at least 50%, by weight, of the total amount of tert-butyl (S)-2-((2S,3R)-1-amino-3-hydroxy-1-oxobutan-2-yl)-1-oxo-2,5-diazaspiro[3.4]octane-5-carboxylate in the pharmaceutical composition.

30 . A solid amorphous form of Compound A:

31 . The solid amorphous form of claim 30 , having an amorphous halo in a powder X-ray diffraction pattern.

32 . The solid amorphous form of claim 30 , having an XRPD pattern that is substantially similar to FIG. 7 .

33 . A pharmaceutical composition comprising the amorphous form of any one of claims 30 to 32 and a pharmaceutically acceptable excipient.

34 . The pharmaceutical composition of claim 33 , wherein the amorphous form is at least 99%, at least 95%, at least 90%, at least 80%, at least 70%, at least 60%, or at least 50%, by weight, of the total amount of tert-butyl (S)-2-((2S,3R)-1-amino-3-hydroxy-1-oxobutan-2-yl)-1-oxo-2,5-diazaspiro[3.4]octane-5-carboxylate in the pharmaceutical composition.

35 . A method of treating a subject in recognized need of treatment for a disease or disorder responsive to NMDA modulation, comprising administering to said subject in need thereof a therapeutically effective amount of a pharmaceutical composition of any one of claims 28 , 29 , 33 , and 34 .

36 . The method of claim 35 , wherein the disease or disorder is selected from autism, anxiety, depression, bipolar disorder, attention deficit disorder, attention deficit hyperactivity disorder (ADHD), schizophrenia, a psychotic disorder, a psychotic symptom, social withdrawal, obsessive-compulsive disorder (OCD), phobia, post-traumatic stress syndrome, a behavior disorder, an impulse control disorder, a substance abuse disorder, a sleep disorder, a memory disorder, a learning disorder, urinary incontinence, multiple system atrophy, progressive supra-nuclear palsy, Friedrich's ataxia, Down's syndrome, fragile X syndrome, tuberous sclerosis, olivio-ponto-cerebellar atrophy, cerebral palsy, drug-induced optic neuritis, ischemic retinopathy, diabetic retinopathy, glaucoma, dementia, AIDS dementia, Alzheimer's disease, Huntington's chorea, spasticity, myoclonus, muscle spasm, Tourette's syndrome, epilepsy, cerebral ischemia, stroke, a brain tumor, traumatic brain injury, cardiac arrest, myelopathy, spinal cord injury, peripheral neuropathy, acute neuropathic pain, and chronic neuropathic pain.

37 . The method of claim 36 , wherein the substance abuse disorder is elected from a withdrawal symptom, opiate addiction, nicotine addiction, and ethanol addition.

38 . The method of claim 36 , wherein the memory disorder is selected from a deficit, loss, and reduced ability to make new memories.

39 . The method of claim 35 , wherein the disease or disorder is major depressive disorder.

40 . A crystal form of tert-butyl (S)-2-((2S,3R)-1-amino-3-hydroxy-1-oxobutan-2-yl)-1-oxo-2,5-diazaspiro[3.4]octane-5-carboxylate dihydrate having an Orthorhombic crystal system, a P2 1 2 1 2 1 space group, and the following unit cell dimensions: a=8.9035 (2)Å, b=10.5404 (2)Å, and c=21.3018 (5)Å, α=β=γ=90°, V=1999.10 (8)Å 3 , Z=4.

41 . A solid crystalline Form II of compound A:

substantially as described herein.

42 . A solid amorphous form of compound A:

substantially as described herein.