Polymorph form of (r)-2-[2-amino-3-(indol-3-yl)propionylamino]-2- methylpropionic acid and uses thereof
AssigneeGalimedix Therapeutics, Inc.
InventorsJozsef Repasi, Andras Szabo, Markus Henrich
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Abstract
This intention relates to a novel polymorph form of compound (R)-2-[2-amino-3-(indol-3-yl)propionylamino]-2-methylpropionic acid, a process for making the novel polymorph form of the compound, and uses thereof for making other polymorph forms of the compound. The invention further relates to composition comprising novel polymorph form of the compound and a pharmaceutically acceptable carrier or excipient.
Claims14
Form II of (R)-2-[2-amino-3-(indol-3-yl)propionylamino]-2-methylpropionic acid, characterized by an X-ray powder diffraction pattern displaying peaks at °2θ (d value Å) angles of 5.87 (15.067), 11.91(7.432), 17.99 (4.931), 30.35 (2.945).
Form II of (R)-2-[2-amino-3-(indol-3-yl)propionylamino]-2-methylpropionic acid, characterized by a single crystal X-ray diffraction pattern having an orthorhombic crystal system and a space group of P 212121.
A method of preparing ultrapure Form I of compound (R)-2-[2-amino-3-(indol-3-yl)propionylamino]-2-methylpropionic acid, characterized by an X-ray powder diffraction pattern displaying peaks at °2θ (d value Å) angles 6.75 (13.095), 10.19 (8.678), 11.76 (7.524), 13.56 (6.531), 17.68 (5.017), 18.63 (4.764), 20.15 (4.407), 22.08 (4.026), wherein the purity of the ultrapure Form I of the compound is from about 99.70 area % to about 99.999 area % by IPC-HPLC, the method comprising
- (a) mixing Form II of the compound with water to prepare a solution of Form II of the compound;
- (b) heating the solution of Form II to about 30-35° C. and cooling to room temperature to produce a precipitate;
- and
- (c) isolating and washing the precipitate to give ultrapure Form I of compound (R)-2-[2-amino-3-(indol-3-yl)propionylamino]-2-methylpropionic acid;
- (d) optionally drying the precipitate at about 45-50° C.
- wherein the purity of the ultrapure Form I of the compound is from about 99.70 area % to about 99.999 area % by IPC-HPLC.
A method for preparing ultrapure Form I of (R)-2-[2-amino-3-(indol-3-yl)propionylamino]-2-methylpropionic acid, characterized by an X-ray powder diffraction pattern displaying peaks at °2θ (d value Å) angles 6.75 (13.095), 10.19 (8.678), 11.76 (7.524), 13.56 (6.531), 17.68 (5.017), 18.63 (4.764), 20.15 (4.407), 22.08 (4.026), wherein said ultrapure Form I of the compound has a purity of from about 99.70 area % to about 99.999 area % by IPC-HPLC, the method comprising
- (a) mixing compound (R)-2-[2-amino-3-(indol-3-yl)propionylamino]-2-methylpropionic acid with an aqueous HCl to provide a solution of the compound;
- (b) cooling the solution to about 5-10° C., followed by adjusting the pH of the solution to about 5.6 with a base;
- (c) stirring the solution at about 0-5° C. until precipitation is complete;
- (d) isolating the resulting precipitate to obtain Form II of the compound;
- (e) mixing the Form II of the compound of step (d) with water to prepare a solution of Form II of the compound;
- (f) heating the solution of Form II of step (e) to about 30-35° C. and cooling to room temperature to produce a precipitate;
- and
- (g) isolating and washing the precipitate to give an ultrapure Form I of the compound;
- wherein the washing step is optionally repeated for two or three times;
- (h) optionally drying at about 45-50° C.;
- and
- (i) optionally repeating steps (a) to (h).
Dependencies are inferred from the claim text.