# US 11,078,231 B2 · Process for purification of carfilzomib intermediate > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,078,231 B2 - Document ID: US11078231B2 - Status: Granted - Kind: B2 - Application number: 16/332,717 - Filed: 2017-09-13 - Published: 2019-07-18 - Granted: 2021-08-03 - Earliest claimed: 2016-09-14 - Assignees: Fresenius Kabi Oncology Limited - Applicants: Fresenius Kabi Oncology Limited - Inventors: Walter Cabri; Saswata Lahiri; Govind Singh; Sarbjot Singh Sokhi; Maneesh Kumar Pandey; Raj Narayan Tiwari; Sonu Prasad Shukla - Web page: https://patentgrep.com/patent/US11078231B2 ## CPC - C07K 1/22: Affinity chromatography or related techniques based upon selective absorption processes - C07C 53/18: containing fluorine - C07D 303/32: by aldehydo- or ketonic radicals - C07K 5/0812: {and aromatic or cycloaliphatic} - C07K 5/1008: {the side chain containing 0 or 1 carbon atoms, i.e. Gly, Ala} - C07K 5/1016: {and aromatic or cycloaliphatic} - A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) - A61P 35/00: Antineoplastic agents - C07B 2200/13: Crystalline forms, e.g. polymorphs - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) - C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS - C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08) - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C07B: GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR (preparation of carboxylic acid esters by telomerisation C07C67/47; telomerisation C08F) ## Abstract The present invention relates to a process for the purification of compound of formula II, wherein X may be independently selected from trifluoroacetic acid, hydrochloric acid, hydrobromic acid, p-toluene sulfonic acid and phosphoric acid; its isolation as solid and use for the preparation of carfilzomib. ## Claims ### Claim 1 A process for purifying a compound of formula II, comprising an impurity of formula III: wherein X is independently trifluoroacetic acid, hydrochloric acid, hydrobromic acid, p-toluene sulfonic acid or phosphoric acid, the process comprising: a) treating the compound of formula II with an alkali metal perhalate in a solvent to reduce the amount of the impurity of Formula III in the compound of Formula II; b) adding an anti-solvent to precipitate the compound of formula II; and c) isolating a substantially pure compound of formula II. ### Claim 2 (depends on 1) The process according to claim 1, wherein the alkali metal perhalate is lithium periodate, sodium periodate, potassium periodate, lithium perbromate, sodium perbromate, potassium perbromate, lithium perchlorate, sodium perchlorate or potassium perchlorate. ### Claim 3 (depends on 1) The process according to claim 1, wherein the solvent is tetrahydrofuran, dioxane, dimethoxyethane, methanol, ethanol, propanol, isopropyl alcohol, n-butanol, ethyl acetate, acetonitrile, propionitrile, dimethylformamide, dimethylacetamide or dimethyl sulfoxide. ### Claim 4 (depends on 1) The process according to claim 1, wherein the anti-solvent is water, n-heptane, n-hexane, methyl tert-butyl ether or diisopropyl ether. ### Claim 5 (depends on 1) The process according to claim 1, wherein ‘X’ is trifluoroacetic acid. ### Claim 6 (depends on 1) The process according to claim 1, further comprising converting the substantially pure compound of formula II into carfilzomib of formula I, ### Claim 7 (depends on 6) The process according to claim 6, further comprising isolating the carfilzomib. ### Claim 8 (depends on 7) The process according to claim 7, wherein the isolated carfilzomib contains less than 0.15 area-% of diol carfilzomib impurity as measured by high performance liquid chromatography (HPLC). ### Claim 9 (depends on 1) The process of claim 1, comprising: i) treating the compound of formula II, wherein X is trifluoroacetic acid (Formula IIa), with an alkali metal perhalate comprising sodium periodate in a solvent comprising tetrahydrofuran, to reduce the amount of the impurity of Formula III in the compound of Formula II; ii) adding water as an anti-solvent to precipitate the compound of formula IIa; and iii) isolating substantially pure compound of formula IIa. ### Claim 10 (depends on 1) The process of claim 1, wherein: the alkali metal perhalate comprises lithium periodate, sodium periodate, potassium periodate, lithium perbromate, sodium perbromate, potassium perbromate, lithium perchlorate, sodium perchlorate or potassium perchlorate; the solvent comprises tetrahydrofuran, dioxane, dimethoxyethane, methanol, ethanol, propanol, isopropyl alcohol, n-butanol, ethyl acetate, acetonitrile, propionitrile, dimethylformamide, dimethylacetamide, or dimethyl sulfoxide; and the anti-solvent comprises water, n-heptane, n-hexane, methyl tert-butyl ether or diisopropyl ether. ### Claim 11 (depends on 7) The process of claim 7, wherein the carfilzomib comprises less than 0.15 area-% of the impurity of formula III as measured by high performance liquid chromatography (HPLC). ### Claim 12 (depends on 7) The process of claim 7, wherein the carfilzomib comprises less than 0.10 area-% of the impurity of formula III as measured by high performance liquid chromatography (HPLC). ### Claim 13 (depends on 7) The process of claim 7, wherein the carfilzomib comprises less than 0.05 area-% of the impurity of formula III as measured by high performance liquid chromatography (HPLC).