4492-02-8

Basic information

• Product Name: 4,5,6,7-TETRAHYDRO-1H-INDAZOLE-3-CARBOXYLIC ACID ETHYL ESTER
• Synonyms: AKOS PAO-0218;4,5,6,7-TETRAHYDRO-1H-INDAZOLE-3-CARBOXYLIC ACID ETHYL ESTER;ETHYL 4,5,6,7-TETRAHYDRO-1H-INDAZOLE-3-CARBOXYLATE
• CAS NO: 4492-02-8
• Molecular Formula: C₁₀H₁₄N₂O₂
• Molecular Weight: 194.23
• Mol File: 4492-02-8.mol
• Article Data: 16

Chemical Properties

• Melting Point: 88 °C(Solv: ligroine (8032-32-4))
• Boiling Point: 403.5±45.0 °C(Predicted)
• Appearance: /
• Density: 1 +-.0.06 g/cm3(Predicted)
• Storage Temp.: 2-8°C
• PKA: 12.36±0.20(Predicted)
• CAS DataBase Reference: 4,5,6,7-TETRAHYDRO-1H-INDAZOLE-3-CARBOXYLIC ACID ETHYL ESTER(CAS DataBase Reference)
• NIST Chemistry Reference: 4,5,6,7-TETRAHYDRO-1H-INDAZOLE-3-CARBOXYLIC ACID ETHYL ESTER(4492-02-8)
• EPA Substance Registry System: 4,5,6,7-TETRAHYDRO-1H-INDAZOLE-3-CARBOXYLIC ACID ETHYL ESTER(4492-02-8)

Safety Data

• Hazardous Substances Data: 4492-02-8(Hazardous Substances Data)

Usage

General Description

4,5,6,7-Tetrahydro-1H-indazole-3-carboxylic acid ethyl ester is a chemical compound with the molecular formula C11H14N2O2. It is an ester derivative of indazole-3-carboxylic acid, with an ethyl group attached to the carboxylic acid functional group. 4,5,6,7-TETRAHYDRO-1H-INDAZOLE-3-CARBOXYLIC ACID ETHYL ESTER is commonly used in organic synthesis as a building block for the preparation of various pharmaceuticals and drug candidates. It is also known for its potential pharmacological properties, including its ability to modulate the activity of certain biological targets, making it a subject of interest for medicinal chemistry research. Due to its versatile applications in chemical and pharmaceutical industries, 4,5,6,7-Tetrahydro-1H-indazole-3-carboxylic acid ethyl ester is considered an important intermediate in organic chemistry.

Synthetic route

ethyl 2-oxo-2-(2-oxocyclohexyl)acetate (5396-14-5) → ethyl 4,5,6,7-tetrahydro-1H-indazole-3-carboxylate (4492-02-8)

Conditions	Yield
With hydrazine hydrate; acetic acid at 0℃; Reflux;	98%
With acetic acid; hydrazine for 1h; Reflux;	86%
With acetic acid; hydrazine for 1h; Reflux;	86%

ethyl diazoacetate + 2-(trimethylsilyl)cyclohexen-1-yl triflate (207505-17-7) → ethyl 4,5,6,7-tetrahydro-1H-indazole-3-carboxylate (4492-02-8)

Conditions	Yield
With cesium fluoride In tetrahydrofuran at 60℃; for 24h; Inert atmosphere;	98%

diazoacetic acid ethyl ester (623-73-4) + cyclohexanone (108-94-1) → ethyl 4,5,6,7-tetrahydro-1H-indazole-3-carboxylate (4492-02-8)

Conditions	Yield
With pyrrolidine In dimethyl sulfoxide at 20℃; for 12h; Solvent; Reagent/catalyst; regioselective reaction;	87%
With pyrrolidine at 80℃;	21%

ethyl 2-(cyclohex-1-en-1-yl)-2-diazoacetate (126580-14-1) → ethyl 4,5,6,7-tetrahydro-1H-indazole-3-carboxylate (4492-02-8)

Conditions	Yield
In octane at 110℃; for 1h;	65%
In octane at 110℃; for 1h;	59%

cyclohexanone (ethoxycarbonyl)hydrazone (6971-92-2) + oxalic acid diethyl ester (95-92-1) → ethyl 4,5,6,7-tetrahydro-1H-indazole-3-carboxylate (4492-02-8)

Conditions	Yield
Stage #1: cyclohexanone (ethoxycarbonyl)hydrazone With n-butyllithium In tetrahydrofuran; hexane at -78 - 20℃; for 1.16667h; Stage #2: oxalic acid diethyl ester In tetrahydrofuran; hexane at -78 - 20℃; for 16h; Stage #3: With sulfuric acid In toluene for 8h; Heating; Further stages.;	43%
Stage #1: cyclohexanone (ethoxycarbonyl)hydrazone With n-butyllithium In tetrahydrofuran; hexane at -78 - 20℃; for 1h; Stage #2: oxalic acid diethyl ester In tetrahydrofuran; hexane at -78 - 20℃; for 16h; Stage #3: With toluene-4-sulfonic acid In toluene for 8h; Heating; Further stages.;	43%

diazoacetic acid ethyl ester (623-73-4) + 1-(1-Cyclohexen-1-yl)pyrrolidine (1125-99-1) → ethyl 4,5,6,7-tetrahydro-1H-indazole-3-carboxylate (4492-02-8)

Conditions	Yield
With chloroform

cyclohexanone (108-94-1) + 1--pyridium iodide → ethyl 4,5,6,7-tetrahydro-1H-indazole-3-carboxylate (4492-02-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: EtONa / ethanol / 18 h / 20 °C 2: N2H4*H2O; AcOH / 8 h / Heating View Scheme

1-hydroxy-1-ethoxycarbonyl-diazomethylcyclohexane (27262-60-8) → ethyl 4,5,6,7-tetrahydro-1H-indazole-3-carboxylate (4492-02-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: 84 percent / phosphoryl chloride, pyridine / 6.5 h / 0 °C 2: 59 percent / octane / 1 h / 110 °C View Scheme
Multi-step reaction with 2 steps 1: 80 percent / POCl3, pyridine / 1) 0 deg C, 6 h, 2) r.t., 12 h 2: 65 percent / octane / 1 h / 110 °C View Scheme
Stage #1: 1-hydroxy-1-ethoxycarbonyl-diazomethylcyclohexane With pyridine; trichlorophosphate at 20℃; Stage #2: In octane at 110℃;

cyclohexanone (108-94-1) + 1.1'-dinitro-dicyclohexyl → ethyl 4,5,6,7-tetrahydro-1H-indazole-3-carboxylate (4492-02-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: 88 percent / lithium diisopropylamide / hexane; tetrahydrofuran / 2 h / -78 °C 2: 84 percent / phosphoryl chloride, pyridine / 6.5 h / 0 °C 3: 59 percent / octane / 1 h / 110 °C View Scheme

cyclohexanone (108-94-1) → ethyl 4,5,6,7-tetrahydro-1H-indazole-3-carboxylate (4492-02-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: 1) n-BuLi / 1) ether, THF, -110 deg C, 2) -110 to -25 deg C 2: 80 percent / POCl3, pyridine / 1) 0 deg C, 6 h, 2) r.t., 12 h 3: 65 percent / octane / 1 h / 110 °C View Scheme
Multi-step reaction with 2 steps 1: sodium ethanolate / ethanol / 7 h / 0 - 20 °C 2: hydrazine hydrate; acetic acid / 0 °C / Reflux View Scheme
Multi-step reaction with 2 steps 1: sodium ethanolate / ethanol / 12 h / 20 °C 2: hydrazine; acetic acid / 1 h / Reflux View Scheme
Multi-step reaction with 2 steps 1.1: diisopropylamine; n-butyllithium / tetrahydrofuran; hexane / 1 h / -78 °C 2.1: pyridine; trichlorophosphate / 20 °C 2.2: 110 °C View Scheme
Multi-step reaction with 2 steps 1: sodium / ethanol / 12 h / 0 - 20 °C 2: acetic acid; hydrazine / 1 h / Reflux View Scheme

ethyl 4,5,6,7-tetrahydro-1H-indazole-3-carboxylate (4492-02-8) → ethyl 4,5,6,7-tetrahydro-1H-indazole-3-carbohydrazide (90434-92-7)

Conditions	Yield
With hydrazine hydrate In ethanol for 36h; Reflux;	100%
With hydrazine In ethanol for 24h; Reflux;	64%
With hydrazine In ethanol for 24h; Reflux;	64%

ethyl 4,5,6,7-tetrahydro-1H-indazole-3-carboxylate (4492-02-8) → (4,5,6,7-tetrahydro-1H-indazol-3-yl)methanol (82071-77-0)

Conditions	Yield
With lithium aluminium tetrahydride In tetrahydrofuran at 0 - 20℃;	88%
With tetrahydrofuran; lithium aluminium tetrahydride

ethyl 4,5,6,7-tetrahydro-1H-indazole-3-carboxylate (4492-02-8) → 4,5,6,7-tetrahydro-1H-indazole-3-carboxylic acid (6076-13-7)

Conditions	Yield
With sodium hydroxide In 1,4-dioxane at 20℃; for 18h;	53%

chloroformic acid ethyl ester (541-41-3) + ethyl 4,5,6,7-tetrahydro-1H-indazole-3-carboxylate (4492-02-8) → 4,5,6,7-tetrahydro-indazole-1,3-dicarboxylic acid diethyl ester

ethyl 4,5,6,7-tetrahydro-1H-indazole-3-carboxylate (4492-02-8) → ethyl 1H-indazole-3-carboxylate (4498-68-4)

Conditions	Yield
With palladium on activated charcoal; decalin

benzyl bromide (100-39-0) + ethyl 4,5,6,7-tetrahydro-1H-indazole-3-carboxylate (4492-02-8) → 1-benzyl-4,5,6,7-tetrahydro-1H-indazole-3-carboxylic acid ethyl ester (174180-78-0)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 60℃; for 16h;	1.05 g

ethanol (64-17-5) + benzyl bromide (100-39-0) + ethyl 4,5,6,7-tetrahydro-1H-indazole-3-carboxylate (4492-02-8) + sodium → 1-benzyl-4.5.6.7-tetrahydro-indazole-carboxylic acid-(3) + 2-benzyl-4.5.6.7-tetrahydro-indazole-carboxylic acid-(3)

Conditions	Yield
Verseifen mit alkoh.Natronlauge;

ethyl bromide (74-96-4) + ethanol (64-17-5) + ethyl 4,5,6,7-tetrahydro-1H-indazole-3-carboxylate (4492-02-8) + sodium → 1-ethyl-4.5.6.7-tetrahydro-indazole-carboxylic acid-(3) + 2-ethyl-4.5.6.7-tetrahydro-indazole-carboxylic acid-(3)

Conditions	Yield
Verseifen mit alkoh.Natronlauge;

ethyl 4,5,6,7-tetrahydro-1H-indazole-3-carboxylate (4492-02-8) → 1-Benzyl-3-hydroxymethyl-4,5,6,7-tetrahydro-1H-indazole (82071-69-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1.05 g / K2CO3 / dimethylformamide / 16 h / 60 °C 2: 740 mg / LiAlH4 / tetrahydrofuran / 1.5 h / 20 - 50 °C View Scheme

ethyl 4,5,6,7-tetrahydro-1H-indazole-3-carboxylate (4492-02-8) → 1-Benzyl-3-bromomethyl-4,5,6,7-tetrahydro-1H-indazole (174180-38-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: 1.05 g / K2CO3 / dimethylformamide / 16 h / 60 °C 2: 740 mg / LiAlH4 / tetrahydrofuran / 1.5 h / 20 - 50 °C 3: 39 percent / PPh3, Br2 / CCl4 / 1.5 h / Ambient temperature View Scheme

ethyl 4,5,6,7-tetrahydro-1H-indazole-3-carboxylate (4492-02-8) → 2-[2,4-Dioxo-5-phenyl-3-(4,5,6,7-tetrahydro-1H-indazol-3-ylmethyl)-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl]-N-isopropyl-N-(4-methoxy-phenyl)-acetamide

Conditions	Yield
Multi-step reaction with 5 steps 1: 1.05 g / K2CO3 / dimethylformamide / 16 h / 60 °C 2: 740 mg / LiAlH4 / tetrahydrofuran / 1.5 h / 20 - 50 °C 3: 39 percent / PPh3, Br2 / CCl4 / 1.5 h / Ambient temperature 4: 1.) NaN(TMS)2 / 1.) THF, DMF, 0 deg C, 5 min, 2.) THF, DMF, RT, 3 h 5: 105 mg / formic acid / 10percent Pd/C / ethanol / 3 h / Heating View Scheme

ethyl 4,5,6,7-tetrahydro-1H-indazole-3-carboxylate (4492-02-8) → 2-[2,4-Dioxo-5-phenyl-3-(4,5,6,7-tetrahydro-1-benzyl-1H-indazol-3-ylmethyl)-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl]-N-isopropyl-N-(4-methoxyphenyl)-acetamide (174180-79-1)

Conditions	Yield
Multi-step reaction with 4 steps 1: 1.05 g / K2CO3 / dimethylformamide / 16 h / 60 °C 2: 740 mg / LiAlH4 / tetrahydrofuran / 1.5 h / 20 - 50 °C 3: 39 percent / PPh3, Br2 / CCl4 / 1.5 h / Ambient temperature 4: 1.) NaN(TMS)2 / 1.) THF, DMF, 0 deg C, 5 min, 2.) THF, DMF, RT, 3 h View Scheme

4-methylisopropylbenzene (99-87-6) + ethyl 4,5,6,7-tetrahydro-1H-indazole-3-carboxylate (4492-02-8) → ethyl 1H-indazole-3-carboxylate (4498-68-4)

Conditions	Yield
palladium
palladium

benzyl bromide (100-39-0) + potassium carbonate (584-08-7) + ethyl 4,5,6,7-tetrahydro-1H-indazole-3-carboxylate (4492-02-8) → 1-benzyl-4,5,6,7-tetrahydro-1H-indazole-3-carboxylic acid ethyl ester (174180-78-0)

Conditions	Yield
In N,N-dimethyl-formamide

ethyl 4,5,6,7-tetrahydro-1H-indazole-3-carboxylate (4492-02-8) → N'-[(2-hydroxynaphthalen-1-yl)methylene]-4,5,6,7-tetrahydro-1H-indazole-3-carbohydrazone (303208-18-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: hydrazine hydrate / ethanol / 36 h / Reflux 2: acetic acid / ethanol / 6 h / Reflux View Scheme

ethyl 4,5,6,7-tetrahydro-1H-indazole-3-carboxylate (4492-02-8) → N'-[(2-hydroxyphenyl)methylene]-4,5,6,7-tetrahydro-1H-indazole-3-carbohydrazone (326018-40-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: hydrazine hydrate / ethanol / 36 h / Reflux 2: acetic acid / ethanol / 6 h / Reflux View Scheme
Multi-step reaction with 2 steps 1: hydrazine / ethanol / 24 h / Reflux 2: ethanol / Reflux View Scheme

ethyl 4,5,6,7-tetrahydro-1H-indazole-3-carboxylate (4492-02-8) → N'-[(4-cyanophenyl)methylene]-4,5,6,7-tetrahydro-1H-indazole-3-carbohydrazone (1381840-59-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: hydrazine hydrate / ethanol / 36 h / Reflux 2: acetic acid / ethanol / 6 h / Reflux View Scheme

ethyl 4,5,6,7-tetrahydro-1H-indazole-3-carboxylate (4492-02-8) → N'-[(4-chloro-3-fluorophenyl)methylene]-4,5,6,7-tetrahydro-1H-indazole-3-carbohydrazone (1381840-60-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: hydrazine hydrate / ethanol / 36 h / Reflux 2: acetic acid / ethanol / 6 h / Reflux View Scheme

Upstream product

• 6971-92-2 cyclohexanone (ethoxycarbonyl)hydrazone 
• 95-92-1 oxalic acid diethyl ester 
• 623-73-4 diazoacetic acid ethyl ester 
• 108-94-1 cyclohexanone 
• 64-17-5 ethanol 
• 5396-14-5 ethyl 2-oxo-2-(2-oxocyclohexyl)acetate 
• 207505-17-7 2-(trimethylsilyl)cyclohexen-1-yl triflate 
• 27262-60-8 1-hydroxy-1-ethoxycarbonyl-diazomethylcyclohexane 
• 1125-99-1 1-(1-Cyclohexen-1-yl)pyrrolidine 
• 126580-14-1 ethyl 2-(cyclohex-1-en-1-yl)-2-diazoacetate 

Downstream Products

• 714255-28-4 4,5,6,7-tetrahydro-2H-indazole-3-carboxylic acid 
• 4498-68-4 ethyl 1H-indazole-3-carboxylate 
• 1557231-90-9 N-(1-(3-cyanobenzyl)-1H-pyrazol-4-yl)-4,5,6,7-tetrahydro-1H-indazole-3-carboxamide 
• 1557248-74-4 C₂₅H₃₂N₆O₂Si 
• 90434-92-7 ethyl 4,5,6,7-tetrahydro-1H-indazole-3-carbohydrazide 
• 326018-40-0 N'-[(2-hydroxyphenyl)methylene]-4,5,6,7-tetrahydro-1H-indazole-3-carbohydrazone 
• 303208-18-6 N'-[(2-hydroxynaphthalen-1-yl)methylene]-4,5,6,7-tetrahydro-1H-indazole-3-carbohydrazone 
• 174180-78-0 1-benzyl-4,5,6,7-tetrahydro-1H-indazole-3-carboxylic acid ethyl ester 
• 174180-79-1 2-[2,4-Dioxo-5-phenyl-3-(4,5,6,7-tetrahydro-1-benzyl-1H-indazol-3-ylmethyl)-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl]-N-isopropyl-N-(4-methoxyphenyl)-acetamide 
• 174180-38-2 1-Benzyl-3-bromomethyl-4,5,6,7-tetrahydro-1H-indazole 
• 82071-69-0 1-Benzyl-3-hydroxymethyl-4,5,6,7-tetrahydro-1H-indazole 
• 6076-13-7 4,5,6,7-tetrahydro-1H-indazole-3-carboxylic acid 
• 82071-77-0 3-Hydroxymethyl-4,5,6,7-tetrahydroindazole 
• 1477483-16-1 C₁₇H₂₀N₄O₂ 

Relevant articles and documents

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