5-Acetyl-1H-Pyrazole-3-carboxylic acid
- CAS NO.:1297537-45-1
- Empirical Formula: C6H6N2O3
- Molecular Weight: 154.12
- MDL number: MFCD05864511
- SAFETY DATA SHEET (SDS)
- Update Date: 2024-04-29 14:28:21
What is 5-Acetyl-1H-Pyrazole-3-carboxylic acid?
The Uses of 5-Acetyl-1H-Pyrazole-3-carboxylic acid
5-acetyl-1H-pyrazole-3-carboxylic acid can be used in the industrialization of substances such as polyurethanes. Impurities in this chemical are removed through filtration before it is used for synthesis.
Definition
5-Acetyl-1H-pyrazole-3-carboxylic acid can be considered a valuable building block for other types of organic and medicinal chemistry transformations and is the essential starting material for the preparation of Darolutamide, which is chemically known as N-{(2S)-1-[3-(3-chloro-4- cyanophenyl)-1H-pyrazol-1-yl]propan-2-yl}-5-(1-hydroxyethyl)-1H-pyrazole-3- 10 carboxamide. Orion Corporation and Bayer Health Care developed Darolutamide. It is an anti-androgen medication that is used for the treatment of prostate cancer in men. Recently, a safe and metal-free process using ethyl glycinate hydrochloride as the starting material has been developed to prepare 5-Acetyl-1H-Pyrazole-3-carboxylic acid[1-2].
Synthesis
5-Acetyl-1H-pyrazole-3-carboxylic acid is a chemical compound that is synthesized from hydrazine and acetyl chloride.
Potassium tert-butoxide (102 g) was added lot-wise to the pre-cooled mixture of 3,3-dimethoxybutane-2-one (100 g) in toluene (1000 ml) at 5-10°C and stirred for 45 minutes. Diethyl oxalate (132 g) was added to the mixture at 10-15°C and stirred for 4 hours. Filtered the solid. To the filtered solid water (3000 ml) was added and cooled to 5-10°C. Solution of Hydrazine monohydrochloride (51.8 g) was slowly added to the mixture at 5-10°C and stirred for 4 hrs. Dichloromethane (1000 ml) was added to the mixture at 5-10°C and stirred for 15 minutes. Allowed to heat the mixture to 25-30°C and stirred for 15 minutes. Filtered the mixture through hyflow. Organic layer was separated from the filtrate. Distilled-off the organic layer and co-distilled in n-heptane (50 ml). n-heptane (300 ml) was added to the mixture at 25-30°C. Heated the mixture at 45-50°C and stirred for 1 hrs. Allowed to cool the mixture to 25-30°C and stirred for 3 hours. Filtered the solid. THF (150 ml) was added to the obtained solid. aq. Sodium hydroxide solution was added to the mixture at 10-15°C. Heated the mixture to 55-60°C and stirred for 2 hrs. Allowed to cool the mixture to 25-30°C and stirred for 15 minutes. Separated the aqueous layer from organic layer. Water was added to the aqueous layer at 25-30°C. Cooled the mixture to 20-25°C. Treated the mixture with hydrochloric acid at 20-25°C. Allowed to heat the mixture to 25-30°C and stirred for 4 hours. Filtered the solid and dried. Tetrahydrofuran (300 ml) was added to the obtained solid at 25-30°C. Heated the mixture to 50-55°C and stirred for 60 minutes. Allowed to cool the mixture to 25-30°C and stirred for 3 hours. Filtered the solid and dried to get 5-Acetyl-1H-pyrazole-3-carboxylic acid, Yield: 63 gm Purity by HPLC: 99.93%.
References
[1] László Poszávácz. "New, Scalable Process for the Preparation of 5-Acetyl-1 H -pyrazole-3-carboxylic Acid, a Key Intermediate of Darolutamide." Synthesis-Stuttgart 33 2 (2023): 2061–2069.
[2] Bence Szilágyi. "Safe and Efficient Continuous-Flow Synthesis and Batchwise Hydrolysis of Ethyl 5-Acetyl-1 H -pyrazole-3-carboxylate: A Key Synthon of Darolutamide." Synthesis-Stuttgart 212 1 (2022): 959–966.
Properties of 5-Acetyl-1H-Pyrazole-3-carboxylic acid
Melting point: | 257-269 °C (decomp)(Solv: ethanol (64-17-5); benzene (71-43-2)) |
Boiling point: | 479.2±30.0 °C(Predicted) |
Density | 1.467±0.06 g/cm3(Predicted) |
storage temp. | 2-8°C |
pka | 3.60±0.10(Predicted) |
InChI | InChI=1S/C6H6N2O3/c1-3(9)4-2-5(6(10)11)8-7-4/h2H,1H3,(H,7,8)(H,10,11) |
Safety information for 5-Acetyl-1H-Pyrazole-3-carboxylic acid
Signal word | Warning |
Pictogram(s) |
Exclamation Mark Irritant GHS07 |
GHS Hazard Statements |
H302:Acute toxicity,oral H315:Skin corrosion/irritation H319:Serious eye damage/eye irritation H335:Specific target organ toxicity, single exposure;Respiratory tract irritation |
Precautionary Statement Codes |
P261:Avoid breathing dust/fume/gas/mist/vapours/spray. P280:Wear protective gloves/protective clothing/eye protection/face protection. P301+P312:IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell. P302+P352:IF ON SKIN: wash with plenty of soap and water. P305+P351+P338:IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing. |
Computed Descriptors for 5-Acetyl-1H-Pyrazole-3-carboxylic acid
InChIKey | HFBWRCZRDIVAMQ-UHFFFAOYSA-N |
SMILES | N1C(C(C)=O)=CC(C(O)=O)=N1 |
New Products
6-Bromo 2-Iodo Indole Pyridine 2,4,6-Tricarboxaldehyde Fosfomycin EP impurity D Ivermectin EP Impurity B Rimegepant Impurity 3 Tubulysin D 2,2-diethoxyethanethioamide (R)-tert-butyl (4-methyl-1-oxopentan-3-yl)carbamate Tubulysin E Tubulysin C 2,3-Dibromo-5,6-dimethylpyridine 4-(Chloromethyl)-7-Hydroxy-2H-chromen-2-one QUINUCLIDINE-2-CARBONITRILE quinuclidine-2-carboxylicacid HCl 2-fluoro-5-(Methylsurfonyl)benzoic acid 2-chloro-4-fluoro-5-Iodobenzophenon Imeglimin Hydrochloride IH 2-[[(3aR,4S,6R,6aS)-6-Aminotetrahydro-2,2-dimethyl-4H-cyclopenta-1,3-dioxol-4-yl]oxy]ethanol ethanedioate Calcium Sodium Phosphosilicate IH Fuel shell 2-(1-(Mercaptomethyl) cyclopropyl) acetonitrile 2-[2-[3(S)-3[2-(7-chloro-2-quinolinyl) ethenyl] phenyl-3- hydroxyl propyl] phenyl]-2-propanol 4-Bromo-N,N-bis(4-iodophenyl)aniline 3,6-Bis(4-bromophenyl)pyrrolo[3,4-c]pyrrole-1,4(2H,5H)-dioneYou may like
-
1297537-45-1 5-ACETYL-1H-PYRAZOLE-3-CARBOXYLIC ACID 99%View Details
1297537-45-1 -
51-80-9 Bis(dimethylamino)mathane 98%View Details
51-80-9 -
42437-96-7 98%View Details
42437-96-7 -
2-bromo-3-methoxy-6-methylpyridine 98%View Details
24207-22-5 -
591-31-1 98%View Details
591-31-1 -
21739-92-4 2-chloro-5-Bromo benzoic acid 98%View Details
21739-92-4 -
R(+)2-(Di phenyl methyl)Pyrrolidine 22348-31-8 98%View Details
22348-31-8 -
228410-90-0 5-bromo-4-methyl-3-nitropyridin-2-ol 98%View Details
228410-90-0