40187-51-7

Basic information

• Product Name: 5-Acetylsalicylamide
• Synonyms: 5-Acetylsalicyamide;LABOTEST-BB LT00012659;5-ACETYLSALICYLAMIDE;5-ACETYL-2-HYDROXYBENZAMIDE;5-Acetosalicylamide;5-Acetylsalicylamide/5-Acetosalicylamide;5-Acetyl;2-Hydroxy-5-acetylbenzamide
• CAS NO: 40187-51-7
• Molecular Formula: C₉H₉NO₃
• Molecular Weight: 179.17
• EINECS: 254-830-5
• Product Categories: Aromatic Carboxylic Acids, Amides, Anilides, Anhydrides & Salts
• Mol File: 40187-51-7.mol

Chemical Properties

• Melting Point: 220-222 °C(lit.)
• Boiling Point: 311.69°C (rough estimate)
• Flash Point: 181.4 °C
• Appearance: cream to beige powder
• Density: 1.2822 (rough estimate)
• Vapor Pressure: 3.38E-06mmHg at 25°C
• Refractive Index: 1.5600 (estimate)
• Storage Temp.: Sealed in dry,Room Temperature
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 6.57±0.18(Predicted)
• CAS DataBase Reference: 5-Acetylsalicylamide(CAS DataBase Reference)
• NIST Chemistry Reference: 5-Acetylsalicylamide(40187-51-7)
• EPA Substance Registry System: 5-Acetylsalicylamide(40187-51-7)

Safety Data

• Hazard Codes: Xn
• Statements: 20/21/22-36/37/38-22
• Safety Statements: 26-36-37/39
• WGK Germany: 3
• RTECS: CU8702280
• Hazardous Substances Data: 40187-51-7(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Synthesis:
5-Acetylsalicylamide is used as a reagent for the synthesis of Phosphotyrosine (P365000) peptidomimetic prodrugs. These prodrugs are designed to have a similar structure to small protein-like chains in order to mimic peptide activities, which can be beneficial for various therapeutic applications.
Additionally, 5-Acetylsalicylamide is used as a reagent to prepare 4-aminopiperidine ureas. These compounds act as human β3 adrenergic receptor agonists, which can be utilized in the development of medications targeting specific conditions related to the adrenergic system.

InChI:InChI=1/C9H9NO3/c1-5(11)6-2-3-8(12)7(4-6)9(10)13/h2-4,12H,1H3,(H2,10,13)

Synthetic route

acetyl chloride (75-36-5) + salicylamide (65-45-2) → 5-acetylsalicylamide (40187-51-7)

Conditions	Yield
With aluminum (III) chloride In nitromethane; dichloromethane at 0 - 20℃; Friedel-Crafts Acylation;	95%
With aluminum (III) chloride; sodium chloride at 140℃; for 0.666667h; Temperature; Reagent/catalyst;	92.2%
Stage #1: salicylamide With aluminum (III) chloride; sodium chloride In water at 180℃; for 3h; Stage #2: acetyl chloride In water at 180℃; for 4h;	88.5%
With aluminium trichloride

O-acetylsalicylamide (5663-71-8) → 5-acetylsalicylamide (40187-51-7)

Conditions	Yield
With aluminium trichloride

(3-Carbamoyl-4-hydroxy-benzyl)-carbamic acid tert-butyl ester → 5-acetylsalicylamide (40187-51-7)

5-acetylsalicylamide (40187-51-7) + (bromomethylcyclohexane) (2550-36-9) → 5-acetyl-2-(cyclohexylmethoxy)benzamide (189393-76-8)

Conditions	Yield
Stage #1: 5-acetylsalicylamide With caesium carbonate In methanol; water for 0.5h; Metallation; Stage #2: Cyclohexylmethyl bromide In N,N-dimethyl-formamide at 90℃; for 42h; Alkylation;	98%

5-acetylsalicylamide (40187-51-7) + benzyl bromide (100-39-0) → 5-acetyl-2-(phenylmethoxy)benzamide (75637-30-8)

Conditions	Yield
With potassium carbonate In acetonitrile Reflux;	98%
With potassium carbonate In acetonitrile Reflux;	98%
With sodium methylate In methanol	80%

5-acetylsalicylamide (40187-51-7) → 5-acetylbenzo[d]oxazol-2(3H)-one (54209-84-6)

Conditions	Yield
With [bis(acetoxy)iodo]benzene; potassium hydroxide In methanol at 0℃; for 1.08333h; Hofmann Rearrangement;	89%

5-acetylsalicylamide (40187-51-7) + 4-fluorobenzaldehyde (459-57-4) → (E)-5-(3-(4-fluorophenyl)acryloyl)-2-hydroxybenzamide

Conditions	Yield
With thionyl chloride In ethanol at 25℃; for 14h;	83%
With thionyl chloride In ethanol at 25℃; for 24h; Claisen-Schmidt Condensation;

5-acetylsalicylamide (40187-51-7) → 5-(2-bromoacetyl)-2-hydroxybenzamide (73866-23-6)

Conditions	Yield
With hydrogen bromide; bromine In ethyl acetate at 5 - 10℃; for 18h;	69.4%
With phenyltrimethylammonium tribromide In methanol; dichloromethane at 20℃;	29%
Stage #1: 5-acetylsalicylamide With copper(I) bromide In ethyl acetate under 760.014 Torr; Inert atmosphere; Stage #2: under 760.014 Torr;

5-acetylsalicylamide (40187-51-7) + 2,2-dimethoxy-propane (77-76-9) → 6-Acetyl-2,2-dimethyl-2,3-dihydro-benzo[e][1,3]oxazin-4-one (142167-24-6)

Conditions	Yield
With toluene-4-sulfonic acid In acetone Heating;	36%

5-acetylsalicylamide (40187-51-7) + ethylene dibromide (106-93-4) → C11H12BrNO3

Conditions	Yield
With N-benzyl-N,N,N-triethylammonium chloride; potassium carbonate In ethyl acetate Reflux;	35%

5-acetylsalicylamide (40187-51-7) + benzyl chloride (100-44-7) → 5-acetyl-2-(phenylmethoxy)benzamide (75637-30-8)

Conditions	Yield
With sodium methylate 1.) DMF, 2.) DMF, heating, 7 h; Yield given. Multistep reaction;

trifluoromethylsulfonic anhydride (358-23-6) + 5-acetylsalicylamide (40187-51-7) → trifluoro-methanesulfonic acid 4-acetyl-2-carbamoyl-phenyl ester

Conditions	Yield
With triethylamine at -40℃;

5-acetylsalicylamide (40187-51-7) → 4-(2-furyl)-3-(carboxamido)phenyl-1-ethanone (343339-00-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: Et3N / -40 °C 2: Pd(PPh3)4; LiCl / dioxane / 110 °C View Scheme

5-acetylsalicylamide (40187-51-7) → 1-[4-(2-furyl)3-(carboxamido)phenyl]-4,4,4-trifluoro-1,3-butanedione (343339-01-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: Et3N / -40 °C 2: Pd(PPh3)4; LiCl / dioxane / 110 °C 3: NaOMe / 1,2-dimethoxy-ethane / 20 °C View Scheme

5-acetylsalicylamide (40187-51-7) → 2-furan-2-yl-5-[2-(5-methanesulfonyl-pyridin-2-yl)-5-trifluoromethyl-2H-pyrazol-3-yl]-benzamide

Conditions	Yield
Multi-step reaction with 4 steps 1: Et3N / -40 °C 2: Pd(PPh3)4; LiCl / dioxane / 110 °C 3: NaOMe / 1,2-dimethoxy-ethane / 20 °C 4: ethanol / Heating View Scheme

5-acetylsalicylamide (40187-51-7) → 2-furan-2-yl-5-[1-(5-methanesulfonyl-pyridin-2-yl)-5-trifluoromethyl-1H-pyrazol-3-yl]-benzamide

Conditions	Yield
Multi-step reaction with 4 steps 1: Et3N / -40 °C 2: Pd(PPh3)4; LiCl / dioxane / 110 °C 3: NaOMe / 1,2-dimethoxy-ethane / 20 °C 4: ethanol / Heating View Scheme

5-acetylsalicylamide (40187-51-7) → 2-hydroxy-5-(1,3-thiazol-5-yl)-benzamide

Conditions	Yield
Multi-step reaction with 2 steps 1: 69.4 percent / HBr; bromine / ethyl acetate / 18 h / 5 - 10 °C 2: 36 percent / ethanol / 6 h / Heating View Scheme

5-acetylsalicylamide (40187-51-7) → 2-hydroxy-5-(2-methyl-thiazol-5-yl)-benzamide (799280-24-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 69.4 percent / HBr; bromine / ethyl acetate / 18 h / 5 - 10 °C 2: 75 percent / ethanol / 6 h / Heating View Scheme

5-acetylsalicylamide (40187-51-7) → 5-(2-amino-thiazol-5-yl)-2-hydroxy-benzamide (799280-23-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: 69.4 percent / HBr; bromine / ethyl acetate / 18 h / 5 - 10 °C 2: 65 percent / ethanol / 6 h / Heating View Scheme

5-acetylsalicylamide (40187-51-7) → 2-hydroxy-5-(2-isopropyl-1,3-thiazol-5-yl)-benzamide

Conditions	Yield
Multi-step reaction with 2 steps 1: 69.4 percent / HBr; bromine / ethyl acetate / 18 h / 5 - 10 °C 2: 46 percent / ethanol / 6 h / Heating View Scheme

5-acetylsalicylamide (40187-51-7) → 5-(2-methyl-thiazol-5-yl)-2-propoxy-benzamide

Conditions	Yield
Multi-step reaction with 3 steps 1: 69.4 percent / HBr; bromine / ethyl acetate / 18 h / 5 - 10 °C 2: 75 percent / ethanol / 6 h / Heating 3: 90 percent / potassium carbonate / dimethylformamide / 60 °C View Scheme

5-acetylsalicylamide (40187-51-7) → 5-(2-amino-thiazol-5-yl)-2-propoxy-benzamide

Conditions	Yield
Multi-step reaction with 3 steps 1: 69.4 percent / HBr; bromine / ethyl acetate / 18 h / 5 - 10 °C 2: 65 percent / ethanol / 6 h / Heating 3: 92 percent / potassium carbonate / dimethylformamide / 60 °C View Scheme

5-acetylsalicylamide (40187-51-7) → 2-butoxy-5-(2-methyl-thiazol-5-yl)-benzamide

Conditions	Yield
Multi-step reaction with 3 steps 1: 69.4 percent / HBr; bromine / ethyl acetate / 18 h / 5 - 10 °C 2: 75 percent / ethanol / 6 h / Heating 3: 94 percent / potassium carbonate / dimethylformamide / 60 °C View Scheme

5-acetylsalicylamide (40187-51-7) → 2-hydroxy-5-[2-(pyridin-2-ylamino)-thiazol-5-yl]-benzamide

Conditions	Yield
Multi-step reaction with 2 steps 1: 69.4 percent / HBr; bromine / ethyl acetate / 18 h / 5 - 10 °C 2: 57 percent / ethanol / 6 h / Heating View Scheme

5-acetylsalicylamide (40187-51-7) → 2-hydroxy-5-(2-phenylamino-thiazol-5-yl)-benzamide (799280-05-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: 69.4 percent / HBr; bromine / ethyl acetate / 18 h / 5 - 10 °C 2: 65 percent / ethanol / 6 h / Heating View Scheme

5-acetylsalicylamide (40187-51-7) → 2-hydroxy-5-(2-o-tolylamino-thiazol-5-yl)-benzamide

Conditions	Yield
Multi-step reaction with 2 steps 1: 69.4 percent / HBr; bromine / ethyl acetate / 18 h / 5 - 10 °C 2: 62 percent / ethanol / 6 h / Heating View Scheme

5-acetylsalicylamide (40187-51-7) → 2-hydroxy-5-(2-p-tolylamino-thiazol-5-yl)-benzamide (799280-07-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: 69.4 percent / HBr; bromine / ethyl acetate / 18 h / 5 - 10 °C 2: 61 percent / ethanol / 6 h / Heating View Scheme

5-acetylsalicylamide (40187-51-7) → 5-[2-(3-chloro-phenylamino)-thiazol-5-yl]-2-hydroxy-benzamide (799280-09-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: 69.4 percent / HBr; bromine / ethyl acetate / 18 h / 5 - 10 °C 2: 52 percent / ethanol / 6 h / Heating View Scheme

5-acetylsalicylamide (40187-51-7) → 5-(2-phenylamino-thiazol-5-yl)-2-propoxy-benzamide

Conditions	Yield
Multi-step reaction with 3 steps 1: 69.4 percent / HBr; bromine / ethyl acetate / 18 h / 5 - 10 °C 2: 65 percent / ethanol / 6 h / Heating 3: 95 percent / potassium carbonate / dimethylformamide / 60 °C View Scheme

5-acetylsalicylamide (40187-51-7) → 5-[2-(4-chloro-phenylamino)-thiazol-5-yl]-2-hydroxy-benzamide

Conditions	Yield
Multi-step reaction with 2 steps 1: 69.4 percent / HBr; bromine / ethyl acetate / 18 h / 5 - 10 °C 2: 49 percent / ethanol / 6 h / Heating View Scheme

5-acetylsalicylamide (40187-51-7) → 2-hydroxy-5-[2-(6-methyl-pyridin-2-ylamino)-thiazol-5-yl]-benzamide

Conditions	Yield
Multi-step reaction with 2 steps 1: 69.4 percent / HBr; bromine / ethyl acetate / 18 h / 5 - 10 °C 2: 68 percent / ethanol / 6 h / Heating View Scheme

Upstream product

• 5663-71-8 O-acetylsalicylamide 
• 75-36-5 acetyl chloride 
• 65-45-2 salicylamide 

Downstream Products

• 75637-30-8 5-acetyl-2-(phenylmethoxy)benzamide 
• 189393-76-8 5-acetyl-2-(cyclohexylmethoxy)benzamide 
• 73866-23-6 5-(2-bromoacetyl)-2-hydroxybenzamide 
• 343339-00-4 4-(2-furyl)-3-(carboxamido)phenyl-1-ethanone 
• 343339-01-5 1-[4-(2-furyl)3-(carboxamido)phenyl]-4,4,4-trifluoro-1,3-butanedione 
• 799280-24-3 2-hydroxy-5-(2-methyl-thiazol-5-yl)-benzamide 
• 799280-23-2 5-(2-amino-thiazol-5-yl)-2-hydroxy-benzamide 
• 799280-05-0 2-hydroxy-5-(2-phenylamino-thiazol-5-yl)-benzamide 
• 799280-07-2 2-hydroxy-5-(2-p-tolylamino-thiazol-5-yl)-benzamide 
• 799280-09-4 5-[2-(3-chloro-phenylamino)-thiazol-5-yl]-2-hydroxy-benzamide 

Relevant articles and documents

Technology for synthesizing 5-acetylsalicylamide

The invention discloses a technology for synthesizing 5-acetylsalicylamide. Methyl salicylate, methyl alcohol, acetylchloride, a self-made modified nano-scale solid acid catalyst and the like are subjected to recrystallization, magnetic stirring, acid treatment and other operation means to prepare the 5-acetylsalicylamide.

5 - acetyl salicylic amide synthesis method

The invention discloses a synthetic method for 5-acetylsalicylamide. The method comprises the following steps: putting anhydrous aluminum chloride and sodium chloride into a container, and performing heating and stirring until both anhydrous aluminum chloride and sodium chloride are fused to obtain low-melting-point NaCl-AlCl3 mixed fused salt; adding salicylamide into the low-melting-point NaCl-AlCl3 mixed fused salt, and stirring until salicylamide is fused; dropwise adding an acylation reagent, and after finishing the dropwise-adding process, producing a heat preservation reaction; immediately and slowly adding acid liquor into an obtained reaction product, and after finishing the process of adding the acid liquor, continuously stirring at the room temperature until no new solids are generated; filtering obtained turbid liquid to obtain a filter cake, and performing washing and drying on the filter cake to obtain a crude product of 5-acetylsalicylamide; purifying the crude product to obtain 5-acetylsalicylamide. The synthetic method for 5-acetylsalicylamide has the advantages of high yield, simple post-treatment, elimination of organic solvents and the like.

New heterocyclic chalcones. Part 6. Synthesis and cytotoxic activities of 5- or 6-(3-aryl- 2-propenoyl)-2(3H)-benzoxazolones

A number of chalcones bearing an oxazole cycle were synthesized by Claisen-Schmidt condensation of 5-acetyl-2(3 H )-benzoxazolone or 6-acetyl-2(3 H )-benzoxazolone and the appropriate aldehydes. The chalcones were evaluated for cytotoxic activity against several tumor cell lines - BV-173 (human B cell precursor leukemia), MCF-7 and MDA-MB-231 (human breast adenocarcinoma) using the MTT-dye reduction assay. The tested compounds exhibit concentration- dependent cytotoxic effects at micromolar concentrations. Exposure of the BV-173 tumor cell line to compound 3f results in strong monoand oligonucleosomal fragmentation of genomic DNA, as evidenced by a 'cell death detection' ELISA kit, which unambiguously indicates that the induction of apoptosis is implicated in the cytotoxic mode of action of the tested compound.

2-aminopyridine derivatives and combinatorial libraries thereof

The present invention relates to novel 2-aminopyridine derivative compounds of the following formula: wherein R1to R5have the meanings provided herein. The invention further relates to combinatorial libraries containing two or more such compounds, as well as methods of preparing 2-aminopyridine derivative compounds.