Solid forms of APOL1 inhibitor and methods of using same
AssigneeVertex Pharmaceuticals Incorporated
InventorsKevin James Gagnon, Jicong Li, Ales Medek, Jack Raphael Minchom, Yi Shi, Muna Shrestha, Faith Witkos
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Abstract
The disclosure provides novel solid state forms of Compound I selected from ethanol solvate Form A, ethanol solvate Form B, citric acid cocrystal Form A, and Form B, compositions comprising the same, and methods of making and using the same, including use in treating APOL1 mediated kidney disease. (I).
Claims28
A solid form of Compound I:
- wherein the solid form is selected from:
- (a) Ethanol solvate Form A;
- (b) Ethanol solvate Form B;
- (c) Citric acid cocrystal Form A;
- and
- (d) Form B.
A method of preparing ethanol solvate Form A of Compound I:
- comprising:
- mixing Compound I Form A with anhydrous ethanol;
- cooling to 5° C. and stirring for about 2 weeks;
- and
- isolating ethanol solvate Form A of Compound I.
A method of preparing ethanol solvate Form B of Compound I:
- comprising:
- mixing Compound I Form A with anhydrous ethanol;
- cooling to 5° C. and stirring for about 2 weeks;
- isolating a wet cake;
- drying under vacuum at 45° C.;
- and
- isolating ethanol solvate Form B of Compound I.
A method of preparing citric acid cocrystal Form A of Compound I:
- comprising:
- combining Compound I Form A and citric acid in a ball mill vessel with propanol/water;
- shaking at 15 Hz for about 30 minutes;
- and
- isolating citric acid cocrystal Form A of Compound I.
A method of preparing Form A of Compound I:
- selected from:
- (a) a method comprising:
- repeated distillation of Compound I in 2-methyltetrahydrofuran;
- heating to 62.5° C. in a solvent comprising methanol for about 35 minutes;
- cooling to 25° C.;
- and
- isolating Form A of Compound I;
- (b) a method comprising:
- mixing Compound I in 2-methyltetrahydrofuran and a solvent comprising methanol;
- heating to 62.5° C. for about 20 minutes;
- charging with heptane over about 1 hour;
- adding seed crystals of Form A of Compound I;
- holding at 62.5° C. for about 1 hour;
- charging with heptane over about 5.5 hours;
- cooling to 25° C.;
- and
- isolating Form A of Compound I;
- or
- (c) a method comprising:
- mixing Compound I in 2-methyltetrahydrofuran and a solvent comprising ethanol;
- heating to 62.5° C. for about 20 minutes;
- charging with heptane over about 5 minutes;
- adding seed crystals of Form A of Compound I;
- holding at 62.5° C. for about 1 hour;
- charging with heptane over about 12 hours;
- cooling to 25° C.;
- and
- isolating Form A of Compound I.
A method of preparing Form B of Compound I:
- comprising:
- exposing Compound I Amorphous Form to heptane vapor at ambient temperature for about 1 month;
- and
- isolating Form B of Compound I.
Dependencies are inferred from the claim text.