4-((6bR,10aS)-3-methyl-2,3,6b,9,10,10a-hexahydro-1H-pyrido[3′,4′:4,5]pyrrolo[1,2,3-de]quinoxalin-8(7H)-yl)-1-(4-fluorophenyl)-1-butanone toluenesulfonic acid addition salt and salt crystals
AssigneeIntra-Cellular Therapies, Inc.
InventorsJohn Tomesch, Lawrence P. Wennogle
Life of this patent
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Abstract
The present invention relates to toluenesulfonic acid addition salt crystals of 4-((6bR,10aS)-3-Methyl-2,3,6b,9,10,10a-Hexahydro-1H-Pyrido[3′,4′:4,5]Pyrrolo[1,2,3-De]Quinoxalin-8(7H)-yl)-1-(4-Fluorophenyl)-1-Butanone, the method of making and using such crystals.
Claims27
A toluenesulfonic acid addition salt crystal of 4-((6bR,10aS)-3-methyl-2,3,6b,9,10,10a-hexahydro-1H-pyrido[3′,4′:4,5]pyrrolo[1,2,3-de]quinoxalin-8(7H)-yl)-1-(4-fluorophenyl)-1-butanone, wherein said salt crystal exhibits an X-ray powder diffraction pattern comprising at least two peaks having 2-theta values selected from the group consisting of 5.68°, 12.11°, 16.04°, 17.03°, 18.16°, 19.00°, 21.67°, 22.55°, 23.48° and 24.30°, wherein the X-ray powder diffraction data is collected on a diffractometer operating with a copper anode with a nickel filter.
A toluenesulfonic acid addition salt crystal of 4-((6bR,l0aS)-3-methyl-2,3,6b,9, 10,10a-hexahydro-1H-pyrido[3′,4′:
- 4,5]pyrrolo[1,2,3-de]quinoxalin-8(7H)-yl)-1-(4-fluorophenyl)-1-butanone, wherein said salt crystal exhibits an X-ray powder diffraction pattern comprising peaks having the following 2-theta values 8.559°, 11.411°, 12.198°, 13.354°, 16.076°, 17.093°, 18.209°, 19.031°, 19.998°, 22.611°, 23.495°, 24.335° and 29.710°, wherein the X-ray powder diffraction data is collected on a diffractometer operating with a copper anode with a nickel filter.
A toluenesulfonic acid addition salt crystal of 4-((6bR,10aS)-3- methyl-2,3,6b,9,10,10a-hexahydro-1H-pyridol[3′,4′:
- 4,5]pyrrolo[1,2,3-de]quinoxalin-8(7H)-yl)-1-(4-fluorophenyl)-1-butanone, wherein said salt crystal exhibits an X-ray powder diffraction pattern comprising the following peaks having 2-theta values:
- 4.1373°, 5.6541°, 8.2430°, 10.3839°, 11.3760°, 12.1103°, 13.3099°, 14.1235°, 14.4743°, 14.8763°, 15.3532°, 15.8535°, 16.4465°, 17.0544°, 17.9466°, 18.1622°, 18.6277°, 18.9621°, 19.8255°, 20.3507°, 20.6196°, 21.6034°, 22.4973°, 23.4609°, 24.3083°, 25.1377°, 26.0351°, 27.2489°, 29.0199°, 31.5733°, 35.0279°, 37.6449° and 39.4614°, wherein the X-ray powder diffraction data is collected on a diffractometer operating with a copper anode with a nickel filter;
- or an X-ray powder diffraction pattern comprising the following peaks having d-spacing values:
- 21.3573 Å, 15,63088 Å, 10.72658 Å, 8.51937 Å, 7.77853 Å, 7.30844 Å, 6.65232 Å, 6.27088 Å, 6.11969 Å, 5.95520 Å, 5.77130 Å, 5.59028 Å, 5.39000 Å, 5.19923 Å, 4.94274 Å, 4.88454 Å, 4.75350 Å, 4.68024 Å, 4.47833 Å, 4.36392 Å, 4.30762 Å, 4.11363 Å, 3.95215 Å, 3.79196 Å, 3.66167 Å, 3.54270 Å, 3.42260 Å, 3.27282 Å, 3.07701 Å, 2.83374 Å, 2.56178 Å, 2.38949 Å and 2.28359 Å.
A toluenesulfonic acid addition salt crystal of 4-((6bR,10aS)-3-methyl-2,3,6b,9,10,10a-hexahydro-1H-pyrido[3′,4′:4,5]pyrrolo[1,2,3-de]quinoxalin-8(7H)-yl)-1-(4-fluorophenyl)-1-butanone, wherein said salt crystal exhibits an X-ray powder diffraction pattern according to FIG. 7, FIG. 7A or FIG. 7B.
A toluenesulfonic acid addition salt crystal of 4-((6bR,10aS)-3-methyl-2,3,6b,9,10,10a-hexahydro-1H-pyrido[3′,4′:4,5]pyrrolo[1,2,3-de]quinoxalin-8(7H)-yl)-1-(4-fluorophenyl)-1-butanone, wherein said salt crystal exhibits a differential scanning calorimetry pattern according to FIG. 8.
A toluenesulfonic acid addition salt crystal of 4-((6bR,10aS)-3-methyl-2,3,6b,9,10,10a-hexahydro-1H-pyrido[3′,4′:4,5]pyrrolo[1,2,3-de]quinoxalin-
A toluenesulfonic acid addition salt crystal of 4-((6bR,10aS)-3-methyl-2,3,6b,9,10,10a-hexahydro-1H-pyrido[3′,4′:4,5]pyrrolo[1,2,3-de]quinoxalin-8(7H)-yl)-1-(4-fluorophenyl)-1-butanone, wherein said salt crystal exhibits an X-ray powder diffraction pattern according to FIG. 7, FIG. 7A or FIG. 7B and a differential scanning calorimetry pattern or a thermogravimetric analysis profile according to FIG. 8.
A toluenesulfonic acid addition salt crystal of 4-((6bR,10aS)-3-methyl-2,3,6b,9,10,10a-hexahydro-1H-pyrido[3′,4′:4,5]pyrrolo[1,2,3-de]quinoxalin-8(7H)-yl)-1-(4-fluorophenyl)-1-butanone, wherein said salt crystal exhibits an X-ray powder diffraction pattern according to FIG. 9 or FIG. 10.
Dependencies are inferred from the claim text.