Claims for Patent: 11,707,456

Summary for Patent: 11,707,456

Title:	Processes for preparing arimoclomol citrate and intermediates thereof
Abstract:	The present disclosure relates to a process for preparing arimoclomol, arimoclomol citrate and key intermediates, such as ORZY-01, thereof. The disclosure further relates to a process for preparing high purity arimoclomol citrate and methods of using the same.
Inventor(s):	Zhe Zhang, Mark Read, Elisabeth Vang CARSTENSEN, Marco POPPE, Andreas Pelz
Assignee:	Zevra Denmark AS
Application Number:	US17/691,989
Patent Claims:	1. A composition comprising: a) at least 98.0% N-{[(2R)-2-hydroxy-3-piperidin-1-ylpropyl]oxy}pyridine-3-carboximidoyl chloride 1-oxide citrate; b) about 1.0% to about 1.9% N-{[(2S)-2-hydroxy-3-piperidin-1-ylpropyl]oxy}pyridine-3-carboximidoyl chloride 1-oxide, or pharmaceutically acceptable salt thereof; and c) about 0.05% to about 0.1% methyl (Z)—N-(2-hydroxy-3-(piperidin-1-yl)propoxy)nicotinimidate 1-oxide, or a pharmaceutically acceptable salt thereof. 2. The composition of claim 1, wherein the composition is a pharmaceutical composition. 3. The pharmaceutical composition of claim 2, wherein the composition further comprises less than 2 ppm N-nitrosopiperidine. 4. The pharmaceutical composition of claim 3, wherein the composition comprises about 0.8 to about 2 ppm N-nitrosopiperidine. 5. An oral formulation comprising the composition of claim 1 and at least one pharmaceutically acceptable excipient. 6. The oral formulation of claim 5, wherein the N-{[(2R)-2-hydroxy-3-piperidin-1-ylpropyl]oxy}pyridine-3-carboximidoyl chloride 1-oxide citrate is present at a dosage from about 50 mg to about 500 mg. 7. The oral formulation of claim 5, wherein the oral formulation comprises from about 20% to about 60% w/w of N-{[(2R)-2-hydroxy-3-piperidin-1-ylpropyl]oxy}pyridine-3-carboximidoyl chloride 1-oxide citrate. 8. The oral formulation of claim 5, comprising N-{[(2R)-2-hydroxy-3-piperidin-1-ylpropyl]oxy}pyridine-3-carboximidoyl chloride 1-oxide citrate at a dosage of about 47 mg, about 62 mg, about 93 mg, or about 124 mg. 9. A unit dosage form of the composition of claim 1 and a pharmaceutically acceptable carrier or excipient. 10. The unit dosage form of claim 9, comprising N-{[(2R)-2-hydroxy-3-piperidin-1-ylpropyl]oxy}pyridine-3-carboximidoyl chloride 1-oxide citrate at a dosage from about 50 mg to about 500 mg. 11. The unit dosage form of claim 9, comprising N-{[(2R)-2-hydroxy-3-piperidin-1-ylpropyl]oxy}pyridine-3-carboximidoyl chloride 1-oxide citrate at a dosage of about 47 mg, about 62 mg, about 93 mg, or about 124 mg. 12. A method of treating Niemann Pick disease, type C in a subject in need thereof, wherein the subject is administered a pharmaceutical composition of claim 2. 13. A method of treating Niemann Pick disease, type C in a subject in need thereof, wherein the subject is administered an oral formulation of claim 5. 14. A method of treating Niemann Pick disease, type C in a subject in need thereof, wherein the subject is administered a unit dosage form of claim 9. 15. A composition comprising: a) at least 98.0% N-{[(2R)-2-hydroxy-3-piperidin-1-ylpropyl]oxy}pyridine-3-carboximidoyl chloride 1-oxide citrate; b) about 1.0% to about 1.9% N-{[(2S)-2-hydroxy-3-piperidin-1-ylpropyl]oxy}pyridine-3-carboximidoyl chloride 1-oxide, or pharmaceutically acceptable salt thereof; and c) about 0.8 to about 2 ppm N-nitrosopiperidine, or a pharmaceutically acceptable salt thereof. 16. The composition of claim 15, wherein the composition is a pharmaceutical composition. 17. The pharmaceutical composition of claim 16, wherein the composition further comprises less than about 0.1% methyl (Z)—N-(2-hydroxy-3-(piperidin-1-yl)propoxy)nicotinimidate 1-oxide, or a pharmaceutically acceptable salt thereof. 18. The pharmaceutical composition of claim 17, wherein the composition comprises about 0.05% to about 0.1% methyl (Z)—N-(2-hydroxy-3-(piperidin-1-yl)propoxy)nicotinimidate 1-oxide, or a pharmaceutically acceptable salt thereof. 19. An oral formulation comprising the composition of claim 15, and at least one pharmaceutically acceptable excipient. 20. The oral formulation of claim 19, wherein the N-{[(2R)-2-hydroxy-3-piperidin-1-ylpropyl]oxy}pyridine-3-carboximidoyl chloride 1-oxide citrate is present at a dosage from about 50 mg to about 500 mg. 21. The oral formulation of claim 19, wherein the oral formulation comprises from about 20% to about 60% w/w of N-{[(2R)-2-hydroxy-3-piperidin-1-ylpropyl]oxy}pyridine-3-carboximidoyl chloride 1-oxide citrate. 22. The oral formulation of claim 19, comprising N-{[(2R)-2-hydroxy-3-piperidin-1-ylpropyl]oxy}pyridine-3-carboximidoyl chloride 1-oxide citrate at a dosage of about 47 mg, about 62 mg, about 93 mg, or about 124 mg. 23. A unit dosage form of the composition of claim 15, and a pharmaceutically acceptable carrier or excipient. 24. The unit dosage form of claim 23, comprising N-{[(2R)-2-hydroxy-3-piperidin-1-ylpropyl]oxy}pyridine-3-carboximidoyl chloride 1-oxide citrate at a dosage from about 50 mg to about 500 mg. 25. The unit dosage form of claim 23, comprising N-{[(2R)-2-hydroxy-3-piperidin-1-ylpropyl]oxy}pyridine-3-carboximidoyl chloride 1-oxide citrate at a dosage of about 47 mg, about 62 mg, about 93 mg, or about 124 mg. 26. A method of treating Niemann Pick disease, type C in a subject in need thereof, wherein the subject is administered a pharmaceutical composition of claim 16. 27. A method of treating Niemann Pick disease, type C in a subject in need thereof, wherein the subject is administered an oral formulation of claim 19. 28. A method of treating Niemann Pick disease, type C in a subject in need thereof, wherein the subject is administered a unit dosage form of claim 23.