# US 2021/0332001 A1 · Synthesis and anti-tumor activities of acyl-para-aminophenol derivatives > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2021/0332001 A1 - Document ID: US20210332001A1 - Status: Published application - Kind: A1 - Application number: 17/308,507 - Filed: 2021-05-05 - Published: 2021-10-28 - Earliest claimed: 2018-11-05 - Assignees: Montefiore Medical Center - Applicants: Montefiore Medical Center - Inventors: Parviz LALEZARI; Rukmani LEKHARJ; Alex LUNA; Diana CASPER - Web page: https://patentgrep.com/patent/US20210332001A1 ## CPC - C07C 231/02: from carboxylic acids or from esters, anhydrides, or halides thereof by reaction with ammonia or amines - C07C 231/24: Separation; Purification - C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS ## Abstract Method are disclosed for synthesizing derivatives of acyl-para-aminophenol and for the use of the compounds for treating lymphomas and tumors of the brain and spinal cord. ## Claims ### Claim 1 A method of synthesizing an acyl-para-aminophenol derivative, the method comprising: i) dissolving para-aminophenol (PAP) in a solvent to form a PAP solution; ii) adding a base to the PAP solution to form a PAP-base solution; iii) adding an acylating agent to the PAP-base solution to form a solution comprising base and PAP precipitates and the acyl-para-aminophenol derivative; iv) removing the base and PAP precipitates from the solution; and v) retrieving the acyl-para-aminophenol derivatives from the solution. ### Claim 2 (depends on 1) The method of claim 1, further comprising crystallizing the acyl-para-aminophenol derivatives. ### Claim 3 (depends on 2) The method of claim 2, wherein the crystallizing comprises suspending the acyl-para-aminophenol derivative in water, then solubilizing the acyl-para-aminophenol derivative by adding an organic solvent to generate crystals of the acyl-para-aminophenol derivative. ### Claim 4 (depends on 3) The method of claim 3, wherein the crystals of the acyl-para-aminophenol derivative are formed by gradual cooling. ### Claim 5 (depends on 3) The method of claim 3, further comprising separating the crystals from the organic solvent and water. ### Claim 6 (depends on 3) The method of claim 3, wherein the organic solvent is an alcohol-based solvent. ### Claim 7 (depends on 6) The method of claim 6, wherein the alcohol-based solvent is selected from the group consisting of ethanol, methanol, and isopropanol. ### Claim 8 (depends on 1) The method of claim 1, wherein the base is an amine. ### Claim 9 (depends on 8) The method of claim 8, wherein the amine is a tertiary amine. ### Claim 10 (depends on 9) The method of claim 9, wherein the tertiary amine is triethylamine (TEA) or diisopropylethylamine (DIPEA). ### Claim 11 (depends on 1) The method of claim 1, wherein the solvent of step i) is an organic solvent. ### Claim 12 (depends on 11) The method of claim 11, wherein the organic solvent is an ether. ### Claim 13 (depends on 12) The method of claim 12, wherein the ether is selected from the group consisting of tetrahydrofuran (THF), diethyl ether, and 1,4-dioxane. ### Claim 14 (depends on 1) The method of claim 1, wherein the PAP is dissolved in about 60 ml to about 80 ml of solvent. ### Claim 15 (depends on 1) The method of claim 1, further comprising stirring the PAP and the solvent at room temperature for about 5 minutes to about 10 minutes. ### Claim 16 (depends on 1) The method of claim 1, wherein about 4 mM to about 10 mM of PAP is dissolved in the solvent. ### Claim 17 (depends on 1) The method of claim 1, wherein about 2 mM to about 3 mM of base is added to the PAP solution. ### Claim 18 (depends on 1) The method of claim 1, further comprising stirring the PAP solution and TEA at room temperature for about 2 minutes to about 5 minutes. ### Claim 19 (depends on 1) The method of claim 1, wherein about 4 mM to about 10 mM of the acylating agent is added to the PAP-base solution. ### Claim 20 (depends on 1) The method of claim 1, further comprising stirring the acylating agent in the PAP-base solution for about 20 minutes to about 40 minutes. ### Claim 21 (depends on 1) The method of claim 1, wherein the acylating agent and PAP-base solution are stirred at room temperature or at about 40° C. to about 70° C. ### Claim 22 (depends on 1) The method of claim 1, wherein the acyl-para-aminophenol derivative is a solid when retrieved from the solution. ### Claim 23 (depends on 1) The method of claim 1, wherein the acylating agent comprises 6-16 carbons and step iii) is carried out at about 60° C. ### Claim 24 (depends on 1) The method of claim 1, wherein the acylating agent is an acetyl, propionyl, butyric, or valéry structure, and step iii) is carried out at room temperature. ### Claim 25 (depends on 1) The method of claim 1, wherein the base is TEA and the base and PAP precipitates are TEA-HCl and PAP-HCl salt precipitates. ### Claim at position 26 26-33. (canceled) ### Claim 34 (depends on 1) The method of claim 1, wherein the acylating agent is selected from the group consisting of acetyl, propionyl, butyryl, isobutyryl, valeryl, hexanoyl, heptanoyl, octanoyl, nonanoyl, decanoyl, dodecanoyl, miristyl, benzoyl, naphthoyl, hexadecanoyl and oleoyl chlorides. ### Claim 35 (depends on 1) The method of claim 1, wherein the acyl-para-aminophenol derivative of acyl-para-aminophenol is selected from the group consisting of acetyl-para-aminophenol, N-(4-hydroxyphenyl)propanamide, N-(4-hydroxyphenyl)-2-methylpropanamide, 4′-Hydroxybutyranilide, N-(4-hydroxyphenyl)pentanamide, N-(4-hydroxyphenyl)benzamide, N-(4-hydroxyphenyl)hexanamide, N-(4-hydroxyphenyl)heptanamide, N-(4-hydroxyphenyl)octanamide, N-(4-hydroxyphenyl)nonanamide, N-(4-hydroxyphenyl)decanamide, N-(4-hydroxyphenyl)-1-naphthamide, N-(4-hydroxyphenyl)-2-naphthamide, N-(4-hydroxyphenyl)dodecanamide, N-(4-hydroxyphenyl)tetradecanamide or N-(4-Hydroxyphenyl)hexadecanamide. ### Claim 36 (canceled) ### Claim 37 A method of treating a brain or spinal cord tumor or a lymphoma in a subject comprising administering to the subject a compound of formula (I) in an amount and manner effective to inhibit the growth of the tumor cells, wherein the compound of formula (I) has the structure: wherein R is a C2-C15 straight chain or branched alkyl, alkenyl, or alkynyl, or a cycloalkyl, heterocycloalky, aryl, heteroaryl, aralkyl, or heteroaralkyl. ### Claim 38 (depends on 37) The method of claim 37, wherein R is a straight chain C6-C8 alkyl. ### Claim 39 (depends on 37) The method of claim 37, wherein the compound is N-(4-hydroxyphenyl)-2-methylpropanamide, 4′-Hydroxybutyranilide, N-(4-hydroxyphenyl)pentanamide, N-(4-hydroxyphenyl)benzamide, N-(4-hydroxyphenyl)hexanamide, N-(4-hydroxyphenyl)heptanamide, N-(4-hydroxyphenyl)octanamide, N-(4-hydroxyphenyl)nonanamide, N-(4-hydroxyphenyl)decanamide, N-(4-hydroxyphenyl)-1-naphthamide, N-(4-hydroxyphenyl)-2-naphthamide, N-(4-hydroxyphenyl)dodecanamide, N-(4-hydroxyphenyl)tetradecanamide or N-(4-Hydroxyphenyl)hexadecanamide. ### Claim 40 (depends on 37) The method of claim 37, wherein the tumor is a glioblastoma multiforme. ### Claim at position 34 41-44. (canceled) ### Claim 45 (depends on 37) The method of claim 37, wherein the compound is used in combination with radiotherapy and/or one or more other chemotherapeutic agents. ### Claim at position 36 46-47. (canceled)