Crystalline solid forms of the acetate salt of (1S,3S,4R)-4-((3AS,4R,5S,7AS)-4-(aminomethyl)-7A-methyl-1-methyleneoctahydro-1H-inden-5-YL)-3- (hydroxymethyl)-4-methylcyclohexanol
The present invention is generally directed to novel crystalline forms of the acetate salt of (1S,3S,4R)-4-((3aS,4R,5S,7aS)-4-(aminomethyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-yl)-3-(hydroxymethyl)-4-methylcyclohexanol and processes for their preparation.
1. A crystalline form of the acetate salt of (1S,3S,4R)-4-((3aS,4R,5S,7aS)-4-(aminomethyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-yl)-3-(hydroxymethyl)-4-methylcyclohexanol, designated as Compound 1 Form B, characterized by an X-ray powder diffraction pattern containing the following peaks: 5.5, 9.4 and 12.2 degrees 2Θ±0.3 degrees 2Θ.
2. The crystalline form of claim 1 further characterized by an X-ray powder diffraction pattern containing one or more of the following additional peaks: 9.0, 12.2, 12.9, 13.2, 14.0, 14.3, 15.4, 16.1, 16.6, 17.0, 18.0, 18.3, 19.0, 20.0, 21.3, 22.8, 24.4, 25.0, 25.8, 26.8, 27.3, 28.1, 28.9, 31.1, 32.5, 33.5, 34.3 and 36.3 degrees 2Θ±0.3 degrees 2Θ.
3. The crystalline form of claim 1 characterized by a DSC with an endothermic event with an onset at 170.4° C.±0.3° C. and a characterizing endothermic peak at 186.6° C.±0.3° C.
4. The crystalline form of claim 1 characterized by one or more of:
XRPD pattern substantially set out in Table 5 and/or FIG. 10 ;
DSC thermogram substantially set out in FIG. 11 ; and
TGA thermogram substantially set out in FIG. 12 .
5. A method for preparing the crystalline form of claim 1 comprising the steps of mixing the amorphous form of the acetate salt of (1S,3S,4R)-4-((3aS,4R,5S,7aS)-4-(aminomethyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-yl)-3-(hydroxymethyl)-4-methylcyclohexanol with solvents of mixtures thereof selected from the group consisting of water and tetrahydrofuran.