53137-27-2

Basic information

• Product Name: 2,4-Dimethylthiazole-5-carboxylic acid
• Synonyms: TIMTEC-BB SBB005433;RARECHEM AL BE 1354;AKOS BBS-00004449;AKOS BB-8977;2,4-DIMETHYL-1,3-THIAZOLE-5-CARBOXYLIC ACID;2,4-DIMETHYL-5-THIAZOLECARBOXYLIC ACID;2,4-DIMETHYLTHIAZOLE-5-CARBOXYLIC ACID;IFLAB-BB F1912-0028
• CAS NO: 53137-27-2
• Molecular Formula: C₆H₇NO₂S
• Molecular Weight: 157.19
• Product Categories: Aromatic Carboxylic Acids, Amides, Anilides, Anhydrides & Salts;Building Blocks;Heterocyclic Building Blocks;Thiazoles
• Mol File: 53137-27-2.mol
• Article Data: 4

Chemical Properties

• Melting Point: 235 °C (dec.)
• Boiling Point: 306.158 °C at 760 mmHg
• Flash Point: 138.96 °C
• Appearance: /
• Density: 1.341 g/cm³
• Vapor Pressure: 0.000342mmHg at 25°C
• Storage Temp.: 2-8°C
• CAS DataBase Reference: 2,4-Dimethylthiazole-5-carboxylic acid(CAS DataBase Reference)
• NIST Chemistry Reference: 2,4-Dimethylthiazole-5-carboxylic acid(53137-27-2)
• EPA Substance Registry System: 2,4-Dimethylthiazole-5-carboxylic acid(53137-27-2)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 22-24/25-37/39-26
• WGK Germany: 3
• HazardClass: IRRITANT
• Hazardous Substances Data: 53137-27-2(Hazardous Substances Data)

Usage

Uses

2,4-Dimethylthiazole-5-carboxylic acid is a highly functionalized and biased thiazole used for drug discovery. It is used as a heterocyclic building block to specifically modify lead compounds.

InChI:InChI=1/C6H7NO2S/c1-3-5(6(8)9)10-4(2)7-3/h1-2H3,(H,8,9)/p-1

Synthetic route

ethyl 2,4-dimethyl-1,3-thiazole-5-carboxylate (7210-77-7) → 2,4-dimethyl-thiazole-5-carboxylic acid (53137-27-2)

Conditions	Yield
With sodium hydroxide In ethanol; water for 4h; Reflux;	90%
With potassium hydroxide
With potassium hydroxide In methanol; water

5-bromo-2,4-dimethyl-1,3-thiazole (28599-52-2) → 2,4-dimethyl-thiazole-5-carboxylic acid (53137-27-2)

Conditions	Yield
With ethanol; phenyllithium Behandeln des Reaktionsgemisches mit CO2;

ethyl 2,4-dimethyl-1,3-thiazole-5-carboxylate (7210-77-7) → 2,4-dimethyl-thiazole-5-carboxylic acid (53137-27-2) + 2,4-dimethyl-thiazole-5-carboxylic acid amide (66806-33-5)

Conditions	Yield
With ammonia

2,4-dimethyl-thiazole-5-carboxylic acid methyl ester; hydrochloride → 2,4-dimethyl-thiazole-5-carboxylic acid (53137-27-2)

Conditions	Yield
With sodium hydroxide at 20℃; Hydrolysis;

2,4-dimethyl-thiazole-5-carboxylic acid (53137-27-2) + tert-butyl alcohol (75-65-0) → tert-butyl (2,4-dimethylthiazol-5-yl)carbamate

Conditions	Yield
With triethanolamine; diphenyl phosphoryl azide at 85℃; for 3h; Inert atmosphere;	96.5%
With diphenyl phosphoryl azide; triethylamine at 85℃; for 4h;	88.54%

1,4-dioxane (123-91-1) + 2,4-dimethyl-thiazole-5-carboxylic acid (53137-27-2) → 1,4-dioxan-2-yl 2,4-dimethylthiazole-5-carboxylate (1597710-80-9)

Conditions	Yield
With iron(III)-acetylacetonate; di-tert-butyl peroxide at 120℃; for 24h; Schlenk technique;	94%

2,4-dimethyl-thiazole-5-carboxylic acid (53137-27-2) + iodobenzene (591-50-4) → 2,4-dimethyl-5-phenylthiazole (19968-55-9)

Conditions	Yield
With silver (II) carbonate; triphenylphosphine; palladium dichloride In N,N-dimethyl acetamide; toluene at 135℃; for 16h; Sealed tube;	93%

2,4-dimethyl-thiazole-5-carboxylic acid (53137-27-2) → potassium 2,4-dimethyl-1,3-thiazole-5-carboxylate (1227469-85-3)

Conditions	Yield
With potassium tert-butylate In ethanol at 20℃; for 3h; Inert atmosphere;	89%

2,4-dimethyl-thiazole-5-carboxylic acid (53137-27-2) + 1-(4-methoxyphenyl)-3-methylpiperazin-2-one hydrochloride → C18H21N3O3S

Conditions	Yield
Stage #1: 2,4-dimethyl-thiazole-5-carboxylic acid With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; Stage #2: 1-(4-methoxyphenyl)-3-methylpiperazin-2-one hydrochloride In N,N-dimethyl-formamide at 20℃; for 3h; Cooling with ice;	88%

2,4-dimethyl-thiazole-5-carboxylic acid (53137-27-2) + 6-(2-aminooxazol-4-yl)-3,4-dihydroquinolin-2(1H)-one → 2,4-dimethyl-N-(4-(2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)oxazol-2-yl)thiazole-5-carboxamide

Conditions	Yield
With pyridine; propylphosphonic anhydride In ethyl acetate; acetonitrile at 50℃; for 120h; Sealed tube;	87%

2,4-dimethyl-thiazole-5-carboxylic acid (53137-27-2) + dichloromethane (75-09-2) → C13H14N2O4S2

Conditions	Yield
With potassium carbonate In dimethyl sulfoxide at 130℃; for 5h;	84%

2,4-dimethyl-thiazole-5-carboxylic acid (53137-27-2) + 3-Methyl-5-pyridin-2-yl-3H-[1,2,3]-triazole-4-carbaldehyde (1374645-80-3) → 2-[2-hydroxy-2-(3-methyl-5-pyridin-2-yl-3H-[1,2,3]triazol-4-yl)-ethyl]-4-methyl-thiazole-5-carboxylic acid (1374645-81-4)

Conditions	Yield
Stage #1: 2,4-dimethyl-thiazole-5-carboxylic acid With n-butyllithium In tetrahydrofuran; hexanes at -75℃; for 2h; Inert atmosphere; Stage #2: 3-Methyl-5-pyridin-2-yl-3H-[1,2,3]-triazole-4-carbaldehyde In tetrahydrofuran; hexanes at -75℃; for 2h; Stage #3: With citric acid In tetrahydrofuran; hexanes; water	83%
Stage #1: 2,4-dimethyl-thiazole-5-carboxylic acid With n-butyllithium In tetrahydrofuran; hexane at -75℃; for 2h; Inert atmosphere; Stage #2: 3-Methyl-5-pyridin-2-yl-3H-[1,2,3]-triazole-4-carbaldehyde In tetrahydrofuran; hexane at -75℃; for 2h;	83%

2,4-dimethyl-thiazole-5-carboxylic acid (53137-27-2) + 6-(2-aminothiazol-4-yl)-3,4-dihydroquinazolin-2(1H)-one → 2,4-dimethyl-N-(4-(2-oxo-1,2,3,4-tetrahydroquinazolin-6-yl)thiazol-2-yl)thiazole-5-carboxamide

Conditions	Yield
With pyridine; propylphosphonic anhydride In ethyl acetate; acetonitrile at 50℃; for 120h; Sealed tube;	82%

2,4-dimethyl-thiazole-5-carboxylic acid (53137-27-2) + tetraethylammonium hydroxide (77-98-5) → tetraethylammonium 2,4-dimethylthiazole-5-carboxylate

Conditions	Yield
In methanol; water at 20℃;	81%

2,4-dimethyl-thiazole-5-carboxylic acid (53137-27-2) + 8-{3-[(2R,6S)-2,6-dimethylmorpholin-4-yl]propoxy}-7-methoxy-2,3-dihydroimidazo[1,2-c]quinazolin-5-amine (1032571-04-2) → N-(8-{3-[(2R,6S)-2,6-dimethylmorpholin-4-yl]propoxyl}-7-methoxy-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)-2,4-dimethyl-1,3-thiazole-5-carboxamide (1032568-41-4)

Conditions	Yield
With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃;	80%

2,4-dimethyl-thiazole-5-carboxylic acid (53137-27-2) + 8-(2-aminothiazol-4-yl)-1,2,5,6-tetrahydro-4H-pyrrolo[3,2,1-ij]quinolin-4-one → 2,4-dimethyl-N-(4-(4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo[3,2,1-ij]quinolin-8-yl)thiazol-2-yl)thiazole-5-carboxamide

Conditions	Yield
With pyridine; propylphosphonic anhydride In ethyl acetate; acetonitrile at 50℃; for 120h; Sealed tube;	79%

2,4-dimethyl-thiazole-5-carboxylic acid (53137-27-2) + 6-(2'-Amino-5'-Methylthiazol-4'-Yl)-3,4-Dihydrocarbostyril → 2,4-dimethyl-N-(5-methyl-4-(2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)thiazol-2-yl)thiazole-5-carboxamide

Conditions	Yield
With pyridine; propylphosphonic anhydride In ethyl acetate; acetonitrile at 50℃; for 144h; Sealed tube;	78%

2,4-dimethyl-thiazole-5-carboxylic acid (53137-27-2) + 4-methylthiosemicarbazide (6610-29-3) → 5-(2,4-dimethyl-1,3-thiazol-5-yl)-4-methyl-2,4-dihydro-3H-1,2,4-triazole-3-thione

Conditions	Yield
Stage #1: 2,4-dimethyl-thiazole-5-carboxylic acid; 4-methylthiosemicarbazide With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; Stage #2: With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide In ethyl acetate; N,N-dimethyl-formamide at 0 - 20℃; for 2h; Stage #3: With hydrogenchloride; sodium hydroxide more than 3 stages;	77%

2,4-dimethyl-thiazole-5-carboxylic acid (53137-27-2) + 5-(4-Fluoro-phenyl)-3-methyl-3H-[1,2,3]-triazole-4-carbaldehyde (1374645-74-5) → 2-{2-[5-(4-fluoro-phenyl)-3-methyl-3H-[1,2,3]triazol-4-yl]-2-hydroxy-ethyl}-4-methyl-thiazole-5-carboxylic acid (1374645-83-6)

Conditions	Yield
Stage #1: 2,4-dimethyl-thiazole-5-carboxylic acid With n-butyllithium In tetrahydrofuran; hexanes at -75℃; for 2h; Inert atmosphere; Stage #2: 5-(4-Fluoro-phenyl)-3-methyl-3H-[1,2,3]-triazole-4-carbaldehyde In tetrahydrofuran; hexanes at -75℃; for 2h; Stage #3: With citric acid In tetrahydrofuran; hexanes; water	77%
Stage #1: 2,4-dimethyl-thiazole-5-carboxylic acid With n-butyllithium In tetrahydrofuran; hexane at -75℃; for 2h; Inert atmosphere; Stage #2: 5-(4-Fluoro-phenyl)-3-methyl-3H-[1,2,3]-triazole-4-carbaldehyde In tetrahydrofuran; hexane at -75℃; for 2h;	77%

2,4-dimethyl-thiazole-5-carboxylic acid (53137-27-2) + 1-(4-methoxyphenyl)-3-phenylpiperazin-2-one → 4-(2,4-dimethyl-1,3-thiazole-5-carbonyl)-1-(4-methoxyphenyl)-3-phenylpiperazin-2-one

Conditions	Yield
Stage #1: 2,4-dimethyl-thiazole-5-carboxylic acid With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 0.5h; Stage #2: 1-(4-methoxyphenyl)-3-phenylpiperazin-2-one In N,N-dimethyl-formamide at 20℃; for 3h; Cooling with ice;	76%

2,4-dimethyl-thiazole-5-carboxylic acid (53137-27-2) + benzylamine (100-46-9) → N-benzyl-2,4-dimethylthiazole-5-carboxamide

Conditions	Yield
Stage #1: 2,4-dimethyl-thiazole-5-carboxylic acid With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 0.5h; Stage #2: benzylamine In N,N-dimethyl-formamide at 20℃; Inert atmosphere;	75.6%

2,4-dimethyl-thiazole-5-carboxylic acid (53137-27-2) + 1-Adamantanamine (768-94-5) → N-(adamantan-1-yl)-2,4-dimethylthiazole-5-carboxamide

Conditions	Yield
Stage #1: 2,4-dimethyl-thiazole-5-carboxylic acid With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 0.5h; Inert atmosphere; Stage #2: 1-Adamantanamine In N,N-dimethyl-formamide at 20℃; Inert atmosphere;	75.2%

2,4-dimethyl-thiazole-5-carboxylic acid (53137-27-2) + 2-(3-aminophenyl)ethan-1-ol (52273-77-5) → N-[3-(2-hydroxyethyl)phenyl]-2,4-dimethyl-1,3-thiazole-5-carboxamide (844904-20-7)

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In DMF (N,N-dimethyl-formamide) for 14h;	73%

2,4-dimethyl-thiazole-5-carboxylic acid (53137-27-2) + 6-(2'-Amino-5'-ethylthiazol-4'-yl)-3,4-dihydrocarbostyril → N-(5-ethyl-4-(2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)thiazol-2-yl)-2,4-dimethylthiazole-5-carboxamide

Conditions	Yield
With pyridine; propylphosphonic anhydride In ethyl acetate; acetonitrile at 50℃; for 144h; Sealed tube;	73%

2,4-dimethyl-thiazole-5-carboxylic acid (53137-27-2) + 1,2,3,4-tetrahydronaphthalen-1-amine (2217-40-5) → 2,4-dimethyl-N-(1,2,3,4-tetrahydronaphthalen-1-yl)thiazole-5-carboxamide

Conditions	Yield
Stage #1: 2,4-dimethyl-thiazole-5-carboxylic acid With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 0.5h; Inert atmosphere; Stage #2: 1,2,3,4-tetrahydronaphthalen-1-amine In N,N-dimethyl-formamide at 20℃; Inert atmosphere;	71.4%

1H-imidazole (288-32-4) + 2,4-dimethyl-thiazole-5-carboxylic acid (53137-27-2) + 2-(thien-3-yl)aminoacetonitrile → 2-(2,4-dimethylthiazole-5-carboxamido)-2-(3-thienyl)acetonitrile (119778-31-3)

Conditions	Yield
With thionyl chloride In tetrahydrofuran; water	70%

2,4-dimethyl-thiazole-5-carboxylic acid (53137-27-2) + 4-iodopyridine (15854-87-2) → 2,4-dimethyl-5-pyridinylthiazole

Conditions	Yield
With silver (II) carbonate; triphenylphosphine; palladium dichloride In N,N-dimethyl acetamide; toluene at 135℃; for 16h; Sealed tube;	70%

2,4-dimethyl-thiazole-5-carboxylic acid (53137-27-2) + Ethyl isocyanoacetate (2999-46-4) → ethyl 5-(2,4-dimethyl-1,3-thiazol-5-yl)-1,3-oxazole-4-carboxylate

Conditions	Yield
Stage #1: 2,4-dimethyl-thiazole-5-carboxylic acid With 1,1'-carbonyldiimidazole In tetrahydrofuran at 20℃; for 2h; Stage #2: Ethyl isocyanoacetate With lithium hexamethyldisilazane In tetrahydrofuran at 0 - 20℃; for 1h;	70%

2,4-dimethyl-thiazole-5-carboxylic acid (53137-27-2) + 3-butyl-4-chloromethyl-5-methyl-isoxazole (1254962-92-9) → 2-[2-(3-butyl-5-methyl-isoxazol-4-yl)-ethyl]-4-methyl-thiazole-5-carboxylic acid (1254970-01-8)

Conditions	Yield
Stage #1: 2,4-dimethyl-thiazole-5-carboxylic acid With lithium diisopropyl amide In tetrahydrofuran at -78℃; Inert atmosphere; Stage #2: 3-butyl-4-chloromethyl-5-methyl-isoxazole In tetrahydrofuran for 1h; Stage #3: With hydrogenchloride In tetrahydrofuran; water	68%
Stage #1: 2,4-dimethyl-thiazole-5-carboxylic acid With n-butyllithium In tetrahydrofuran; hexanes at -78℃; Inert atmosphere; Stage #2: 3-butyl-4-chloromethyl-5-methyl-isoxazole In tetrahydrofuran; hexanes at -75℃; Stage #3: With citric acid In tetrahydrofuran; hexanes

2,4-dimethyl-thiazole-5-carboxylic acid (53137-27-2) + 6-(2-aminothiazol-4-yl)chroman-2-one → 2,4-dimethyl-N-(4-(2-oxochroman-6-yl)thiazol-2-yl)thiazole-5-carboxamide

Conditions	Yield
With pyridine; propylphosphonic anhydride In ethyl acetate; acetonitrile at 48.5℃; for 120h; Sealed tube;	67%

1H-imidazole (288-32-4) + 2,4-dimethyl-thiazole-5-carboxylic acid (53137-27-2) + α-(2-thienyl)aminoacetonitrile (779315-19-4) → 2-(2,4-dimethylthiazole-5-carboxamido)-2-(2-thienyl)acetonitrile (119778-30-2)

Conditions	Yield
With thionyl chloride In tetrahydrofuran; water	65%

2,4-dimethyl-thiazole-5-carboxylic acid (53137-27-2) + (6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-4-yl)-quinolin-3-yl-amine dihydrochloride → (2,4-dimethyl-thiazol-5-yl)-[4-(quinolin-3-ylamino)-5,7-dihydro-pyrrolo[3,4-d]pyrimidin-6-yl]-methanone (1227460-58-3)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; HATU In 1-methyl-pyrrolidin-2-one at 20℃; for 0.0833333h;	64%

2,4-dimethyl-thiazole-5-carboxylic acid (53137-27-2) + 4-chloromethyl-5-methyl-3-phenyl-isoxazole (18718-83-7) → 4-methyl-2-[2-(5-methyl-3-phenyl-isoxazol-4-yl)-ethyl]-thiazole-5-carboxylic acid (1254969-88-4)

Conditions	Yield
Stage #1: 2,4-dimethyl-thiazole-5-carboxylic acid With lithium diisopropyl amide In tetrahydrofuran at -78℃; Inert atmosphere; Stage #2: 4-chloromethyl-5-methyl-3-phenyl-isoxazole In tetrahydrofuran for 1h; Stage #3: With hydrogenchloride In tetrahydrofuran; water	60%

Upstream product

• 28599-52-2 5-bromo-2,4-dimethyl-1,3-thiazole 
• 7210-77-7 ethyl 2,4-dimethyl-1,3-thiazole-5-carboxylate 

Downstream Products

• 113391-64-3 4-methyl-2-propylthiazole-5-carboxylic acid 
• 113366-46-4 2-ethyl-4-methyl-1,3-thiazole-5-carboxylic acid 
• 173841-81-1 methyl 2,4-dimethylthiazole-5-carboxylate 
• 258261-50-6 (2,4-dimethyl-thiazol-5-yl)-(1-trityl-1H-imidazol-4-yl)-methanone 
• 844904-20-7 N-[3-(2-hydroxyethyl)phenyl]-2,4-dimethyl-1,3-thiazole-5-carboxamide 
• 21452-18-6 metsulfovax 
• 637336-36-8 2,4-dimethyl-thiazole-5-carboxylic acid {4-[3-cyclopropylmethyl-1-(2-fluorobenzyl)-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-ylmethyl]-phenyl}-methyl-amide 
• 288080-95-5 C₂₆H₃₄N₆O₃S 
• 288081-17-4 C₂₆H₃₄N₆O₄S 
• 1005784-44-0 N-[2-chloro-5-({2-[(cyclopropylcarbonyl)amino]imidazo[1,2-b]pyridazin-6-yl}oxy)phenyl]-2,4-dimethyl-1,3-thiazole-5-carboxamide 
• 519028-77-4 C₂₃H₂₄FN₅O₄S 
• 519033-06-8 C₂₄H₂₆FN₅O₄S 
• 1186415-57-5 C₁₆H₁₇ClN₂O₃S 

Relevant articles and documents

Structure-activity relationships of thiazole and benzothiazole derivatives as selective cannabinoid CB2 agonists with in vivo anti-inflammatory properties

The strong therapeutic potential of CB2 receptor agonists for use as anti-inflammatory agents that lack psychiatric side effects has attracted substantial interest. We herein describe the rational design and synthesis of novel thiazole and benzothiazole derivatives and the evaluation of their binding affinity and functional activity on CB1 and CB2 receptors. The series with the general formula N-(3-pentylbenzo [d]thiazol-2(3H)-ylidene) carboxamide (compounds 6a-6d) exhibited the highest affinity and selectivity towards CB2 receptors with Kis in the picomolar or low nanomolar range, and selectivity indices (Ki hCB1/Ki hCB2) reaching up to 429 fold. Notably, these compounds also demonstrated an agonistic functional activity in cellular assays with EC50s in the low nanomolar range. More interestingly, compound 6d, the 3-(trifluoromethyl)benzamide derivative, exhibited remarkable protection against DSS-induced acute colitis in mice model.

α2 Adrenoceptor agonists as potential analgesic agents. 1. (Imidazolylmethyl)oxazoles and -thiazoles

A series of (imidazolylmethyl)oxazoles and -thiazoles were prepared and evaluated as α2 adrenoceptor agonists. These compounds were also tested in in vivo paradigms that are predictive of analgesic activity. Variations in both the imidazole and thiazole portions of the molecule were investigated. Some of the more potent compounds such as 22, 26, 45, and 53 displayed α2 receptor binding in the 10-20 nM range and also had significant antinociceptive activity in the mouse abdominal irritant test (MAIT).