4498-67-3

Basic information

• Product Name: Indazole-3-carboxylic acid
• Synonyms: 1H-INDAZOL-3-CARBONIC ACID;1H-INDAZOLE-3-CARBOXYLIC ACID;1H-INDAZOLE-3-CARBONIC ACID;AKOS BB-9978;3-INDAZOLECARBOXYLIC ACID;3-CARBOXYINDAZOLE;ndazole-3-carboxylic acid;INDAZOLE-3-CARBOXYLIC ACID
• CAS NO: 4498-67-3
• Molecular Formula: C₈H₆N₂O₂
• Molecular Weight: 162.15
• EINECS: 224-794-5
• Product Categories: PHARMACEUTICAL INTERMEDIATES;Acids and Derivatives;Heterocycles;Indoles and derivatives;pharmacetical;Carboxylic Acids;Organic acids;(intermediate of granisetron);Indazoles;Indole Derivatives;Carboxylic Acids;Fused Ring Systems;Building Blocks;Heterocyclic Building Blocks
• Mol File: 4498-67-3.mol
• Article Data: 17

Chemical Properties

• Melting Point: 266-270 °C (dec.)
• Boiling Point: 443.7 °C at 760 mmHg
• Flash Point: 222.2 °C
• Appearance: beige/powder
• Density: 1.506 g/cm³
• Vapor Pressure: 1.18E-08mmHg at 25°C
• Refractive Index: 1.743
• Storage Temp.: Refrigerator
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 3.03±0.10(Predicted)
• BRN: 6354
• CAS DataBase Reference: Indazole-3-carboxylic acid(CAS DataBase Reference)
• NIST Chemistry Reference: Indazole-3-carboxylic acid(4498-67-3)
• EPA Substance Registry System: Indazole-3-carboxylic acid(4498-67-3)

Safety Data

• Hazard Codes: Xn,Xi
• Statements: 22-36-36/37/38
• Safety Statements: 26-36/37/39-22
• WGK Germany: 3
• HazardClass: IRRITANT
• Hazardous Substances Data: 4498-67-3(Hazardous Substances Data)

Usage

Chemical Properties

yellow crystal

Uses

Different sources of media describe the Uses of 4498-67-3 differently. You can refer to the following data:
1. Indazole-3-carboxylic acid is indole derivatives useful in treatment of pain and inflammation
2. Indazole-3-carboxylic acid may be used in the synthesis of the following:N-(8-methyl-azabicyclo[3.2.11]oct-3-yl)-1H-indazole-3-carboxamideN-(1- benzyl-4-methylhexahydro-1H-1,4-diazepin-6-yl)-1H-indazole-3-carboxamide1H-indazole-3-carboxamide

Synthesis Reference(s)

Journal of Heterocyclic Chemistry, 26, p. 531, 1989 DOI: 10.1002/jhet.5570260251

InChI:InChI=1/C8H6N2O2/c11-8(12)7-5-3-1-2-4-6(5)9-10-7/h1-4H,(H,9,10)(H,11,12)

Synthetic route

indole-2,3-dione (91-56-5) → 1H-Indazole-3-carboxylic acid (4498-67-3)

Conditions	Yield
Stage #1: indole-2,3-dione With sodium hydroxide In water at 20 - 50℃; for 1.5h; Stage #2: With sulfuric acid; sodium nitrite In water at 0℃; for 1h; Stage #3: With hydrogenchloride; tin(ll) chloride In water for 1.16667h;	100%
With sodium hydroxide; sulfuric acid; sulfur dioxide; sodium nitrite Reagens 4: Zinnchloruer;
With sulfuric acid; sodium nitrite danach SnCl2;

methyl 1-acetylindazole-3-carboxylate (186966-06-3) → 1H-Indazole-3-carboxylic acid (4498-67-3)

Conditions	Yield
With sodium hydroxide In hydrogenchloride; water	100%
With sodium hydroxide; water for 1.5h; Heating;	97%

ethyl 1-acetyl-1H-indazole-3-carboxylate (78155-12-1) → 1H-Indazole-3-carboxylic acid (4498-67-3)

Conditions	Yield
With sodium hydroxide; water for 1.5h; Heating;	98%

1-(3-(morpholine-4-carbonyl)-1H-indazol-1-yl)ethanone (186966-03-0) → 1H-Indazole-3-carboxylic acid (4498-67-3)

Conditions	Yield
With sodium hydroxide; water for 3h; Heating;	96%

4-bromobenzylideneaminoisatine (1630015-70-1) → 1H-Indazole-3-carboxylic acid (4498-67-3)

Conditions	Yield
Stage #1: 4-bromobenzylideneaminoisatine With hydrogenchloride In water; acetic acid at 90 - 100℃; for 1h; Stage #2: With acetic acid at 115℃; for 1h;	85%

1-(benzylideneamino)indoline-2,3-dione (10604-20-3) → 1H-Indazole-3-carboxylic acid (4498-67-3)

Conditions	Yield
With hydrogenchloride; acetic acid In dichloromethane; ISOPROPYLAMIDE; water at 15 - 90℃; Product distribution / selectivity; Reflux; Inert atmosphere;	76%
Stage #1: 1-(benzylideneamino)indoline-2,3-dione With hydrogenchloride; acetic acid In water at 90℃; for 1h; Stage #2: With acetic acid at 115℃; for 0.5h;	71%

3-(hydroxymethyl)-1H-indazole (64132-13-4) → 1H-Indazole-3-carboxylic acid (4498-67-3)

Conditions	Yield
With chromium(VI) oxide; sulfuric acid In acetone at 20℃; for 24h;	64%
With chromium(VI) oxide; sulfuric acid In acetone at 20℃; for 24h;	64%

tin(II)chloride dihydrate + indole-2,3-dione (91-56-5) → 1H-Indazole-3-carboxylic acid (4498-67-3)

Conditions	Yield
With sodium hydroxide; sulfuric acid; sodium nitrite In hydrogenchloride; water	31%

1-dimethylamino-indolin-2-one (861798-91-6) + 2,3-dimethyl-4-nitroso-aniline (871876-73-2) + sodium ethanolate (141-52-6) → 1H-Indazole-3-carboxylic acid (4498-67-3)

1-benzylideneamino-indole-2,3-dione (10604-20-3) + acetic acid (64-19-7) → benzaldehyde (100-52-7) + 1H-Indazole-3-carboxylic acid (4498-67-3)

Conditions	Yield
mit Wasserdampf;

indazole-3-carbonitrile (50264-88-5) → 1H-Indazole-3-carboxylic acid (4498-67-3)

Conditions	Yield
With hydrogenchloride

N-acetylaminoisatin (123704-99-4) → 1H-Indazole-3-carboxylic acid (4498-67-3)

Conditions	Yield
With sulfuric acid for 2.5h; Heating;

sulfuric acid (7664-93-9) + 1-acetylamino-indoline-2,3-dione-3-oxime → 1H-Indazole-3-carboxylic acid (4498-67-3)

N-acetylamino-isatin-β oxime → 1H-Indazole-3-carboxylic acid (4498-67-3)

Conditions	Yield
With sulfuric acid

N-benzylidenamino-isatin → 1H-Indazole-3-carboxylic acid (4498-67-3)

Conditions	Yield
With hydrogenchloride

hydrogenchloride (7647-01-0) + 1-benzylideneamino-indole-2,3-dione (10604-20-3) → benzaldehyde (100-52-7) + 1H-Indazole-3-carboxylic acid (4498-67-3)

Conditions	Yield
mit Wasserdampf;

oxalic acid-(benzylidene-phenyl-hydrazide)-chloride (109411-83-8) → 1H-Indazole-3-carboxylic acid (4498-67-3) + N-benzylidenamino-isatin

Conditions	Yield
With carbon disulfide; aluminium trichloride

2-(2-nitrophenyl)acetic acid (3740-52-1) → 1H-Indazole-3-carboxylic acid (4498-67-3)

Conditions	Yield
Multi-step reaction with 4 steps 1: 95 percent / cc. H2SO4 / 4 h / Heating 2: 97 percent / H2 / 5percent Pd/C / toluene / Ambient temperature 3: 87 percent / 90percent t-BuONO / acetic acid / 0.5 h / 90 - 95 °C 4: 97 percent / NaOH, water / 1.5 h / Heating View Scheme
Multi-step reaction with 4 steps 1: 94 percent / cc. H2SO4 / 4 h / Heating 2: 97 percent / H2 / 5percent Pd/C / toluene / Ambient temperature 3: 83 percent / 90percent t-BuONO / toluene / 0.5 h / 90 - 95 °C 4: 98 percent / NaOH, water / 1.5 h / Heating View Scheme
Multi-step reaction with 4 steps 1: 89 percent / SOCl2 / dimethylformamide; 1,2-dichloro-ethane / 35-40 deg C, 2 h then 20 deg C, 2 h 2: 95 percent / H2 / 5percent Pd/C / toluene / Ambient temperature 3: 76 percent / 90percent t-BuONO / toluene / 0.5 h / 90 - 95 °C 4: 96 percent / NaOH, water / 3 h / Heating View Scheme
Multi-step reaction with 5 steps 1: 89 percent / SOCl2 / dimethylformamide; 1,2-dichloro-ethane / 35-40 deg C, 2 h then 20 deg C, 2 h 2: 92 percent / Fe, aq. NH4Cl / propan-2-ol / 1 h / Heating 3: toluene / rt to 95 deg C 4: 76 percent / 90percent t-BuONO / toluene / 0.5 h / 90 - 95 °C 5: 96 percent / NaOH, water / 3 h / Heating View Scheme

methyl (2-nitrophenyl)acetate (30095-98-8) → 1H-Indazole-3-carboxylic acid (4498-67-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: 97 percent / H2 / 5percent Pd/C / toluene / Ambient temperature 2: 87 percent / 90percent t-BuONO / acetic acid / 0.5 h / 90 - 95 °C 3: 97 percent / NaOH, water / 1.5 h / Heating View Scheme

ethyl 2-nitrophenylacetate (31912-02-4) → 1H-Indazole-3-carboxylic acid (4498-67-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: 97 percent / H2 / 5percent Pd/C / toluene / Ambient temperature 2: 83 percent / 90percent t-BuONO / toluene / 0.5 h / 90 - 95 °C 3: 98 percent / NaOH, water / 1.5 h / Heating View Scheme

(2-acetylamino-phenyl)-acetic acid ethyl ester (186966-08-5) → 1H-Indazole-3-carboxylic acid (4498-67-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 83 percent / 90percent t-BuONO / toluene / 0.5 h / 90 - 95 °C 2: 98 percent / NaOH, water / 1.5 h / Heating View Scheme

methyl 3-(2-acetamidophenyl)propanoate (134810-89-2) → 1H-Indazole-3-carboxylic acid (4498-67-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 87 percent / 90percent t-BuONO / acetic acid / 0.5 h / 90 - 95 °C 2: 97 percent / NaOH, water / 1.5 h / Heating View Scheme

4-[(2-nitro-phenyl)-acetyl]-morpholine (25888-16-8) → 1H-Indazole-3-carboxylic acid (4498-67-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: 95 percent / H2 / 5percent Pd/C / toluene / Ambient temperature 2: 76 percent / 90percent t-BuONO / toluene / 0.5 h / 90 - 95 °C 3: 96 percent / NaOH, water / 3 h / Heating View Scheme
Multi-step reaction with 4 steps 1: 92 percent / Fe, aq. NH4Cl / propan-2-ol / 1 h / Heating 2: toluene / rt to 95 deg C 3: 76 percent / 90percent t-BuONO / toluene / 0.5 h / 90 - 95 °C 4: 96 percent / NaOH, water / 3 h / Heating View Scheme

4-(2-aminophenylacetyl)morpholine (80798-83-0) → 1H-Indazole-3-carboxylic acid (4498-67-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: toluene / rt to 95 deg C 2: 76 percent / 90percent t-BuONO / toluene / 0.5 h / 90 - 95 °C 3: 96 percent / NaOH, water / 3 h / Heating View Scheme

N-[2-(2-Morpholin-4-yl-2-oxo-ethyl)-phenyl]-acetamide (186966-07-4) → 1H-Indazole-3-carboxylic acid (4498-67-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 76 percent / 90percent t-BuONO / toluene / 0.5 h / 90 - 95 °C 2: 96 percent / NaOH, water / 3 h / Heating View Scheme

N-Acetylaminoisonitrosoacetanilide (123704-98-3) → 1H-Indazole-3-carboxylic acid (4498-67-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 96percent H2SO4 / 0.25 h / 85 °C 2: aq. H2SO4 / 2.5 h / Heating View Scheme

1-acetyl-2-phenylhydrazine (114-83-0) → 1H-Indazole-3-carboxylic acid (4498-67-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: 79 percent / hydroxylamine hydrochloride, sodium sulphate, 1 N HCl / H2O / 0.17 h / 100 °C 2: 96percent H2SO4 / 0.25 h / 85 °C 3: aq. H2SO4 / 2.5 h / Heating View Scheme

2-nitro-benzeneacetonitrile (610-66-2) → 1H-Indazole-3-carboxylic acid (4498-67-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: tin; hydrochloric acid 2: acid; sodium nitrite 3: concentrated hydrochloric acid View Scheme

2-aminophenylacetonitrile (2973-50-4) → 1H-Indazole-3-carboxylic acid (4498-67-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: acid; sodium nitrite 2: concentrated hydrochloric acid View Scheme

p-toluidine (106-49-0) + 1H-Indazole-3-carboxylic acid (4498-67-3) → N-(p-tolyl)-1H-indazole-3-carboxamide

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 100℃;	100%
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 100℃; for 10h;	66%

1H-Indazole-3-carboxylic acid (4498-67-3) + 4-methoxycarbonyl aniline (619-45-4) → methyl 4-(1H-indazole-3-carboxamido)benzoate

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 100℃;	100%
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 100℃; for 10h;	10%

4-chloro-aniline (106-47-8) + 1H-Indazole-3-carboxylic acid (4498-67-3) → N-(4-chlorophenyl)-1H-indazole-3-carboxamide (23707-00-8)

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 100℃;	100%

methanol (67-56-1) + 1H-Indazole-3-carboxylic acid (4498-67-3) → methyl 1H-indazole-3-carboxylate (43120-28-1)

Conditions	Yield
With sulfuric acid for 2h; Heating;	98%
With sulfuric acid for 2h; Reflux;	95%
With thionyl chloride for 3h; Reflux;	95%

5,6-diamino-1-ethyl-3,3-dimethylindol-2-one (881693-01-2) + 1H-Indazole-3-carboxylic acid (4498-67-3) → 5-ethyl-2-(1H-indazol-3-yl)-7,7-dimethyl-5,7-dihydro-3H-imidazo[4,5-f]indol-6-one

Conditions	Yield
Stage #1: 5,6-diamino-1-ethyl-3,3-dimethylindol-2-one; 1H-Indazole-3-carboxylic acid With PPA; phosphorus pentoxide at 150℃; for 6h; Stage #2: With ammonia In water pH=7 - 8;	97%

endo-9-methyl-9-azabicyclo[3.3.1]nonan-3-amine (76272-41-8, 141650-55-7, 76272-56-5) + 1H-Indazole-3-carboxylic acid (4498-67-3) → endo-N-(9-methyl-9-azabicyclo<3.3.1>nonan-3-yl)-1H-indazole-3-carboxamide (107007-95-4)

Conditions	Yield
Stage #1: 1H-Indazole-3-carboxylic acid With benzotriazol-1-ol; dicyclohexyl-carbodiimide In dichloromethane; N,N-dimethyl-formamide at 20℃; for 2h; Stage #2: endo-9-methyl-9-azabicyclo[3.3.1]nonan-3-amine In dichloromethane; N,N-dimethyl-formamide at 20℃; Inert atmosphere;	97%
With benzotriazol-1-ol; dicyclohexyl-carbodiimide In dichloromethane; N,N-dimethyl-formamide at 20℃;	73%

1H-Indazole-3-carboxylic acid (4498-67-3) + dimethyl sulfate (77-78-1) → methyl 1H-indazole-3-carboxylate (43120-28-1)

Conditions	Yield
Stage #1: 1H-Indazole-3-carboxylic acid With potassium carbonate In acetone at 20℃; for 0.166667h; Stage #2: dimethyl sulfate In acetone for 4h; Reflux;	95%

Phenylpropargyl aldehyde (2579-22-8) + Benzyl isocyanide (88333-03-3, 10340-91-7) + 1H-Indazole-3-carboxylic acid (4498-67-3) + 4-bromo-aniline (106-40-1) → N,4-dibenzyl-2-(4-bromophenyl)-1-oxo-1,2-dihydropyrazino[1,2-b]indazole-3-carboxamide

Conditions	Yield
Stage #1: Phenylpropargyl aldehyde; 4-bromo-aniline In 2,2,2-trifluoroethanol at 20℃; for 0.166667h; Microwave irradiation; Stage #2: Benzyl isocyanide; 1H-Indazole-3-carboxylic acid In N,N-dimethyl-formamide at 20 - 110℃; Microwave irradiation;	95%

oxetan-3-yl-methylamine (952182-03-5) + 1H-Indazole-3-carboxylic acid (4498-67-3) → N-methyl-N-(oxetan-3-yl)-1H-indazole-3-carboxamide

Conditions	Yield
With triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; for 24h; Reagent/catalyst; Temperature; Solvent;	94%

1H-Indazole-3-carboxylic acid (4498-67-3) + methylamine (74-89-5) → 1-methyl-3-indolecarboxylic acid (32387-21-6)

Conditions	Yield
Stage #1: 1H-Indazole-3-carboxylic acid With tin(ll) chloride In acetonitrile at 55℃; for 6h; Stage #2: methylamine In acetonitrile at 9℃; for 41h; Temperature; Reflux;	93%

tert-butyl [2-amino-2-(hydroxyimino)ethyl]carbamate (479079-15-7, 479080-20-1) + 1H-Indazole-3-carboxylic acid (4498-67-3) → tert-butyl 2-(1H-indazole-3-carbonyloxyimino)-2-aminoethylcarbamate (1151512-97-8)

Conditions	Yield
Stage #1: 1H-Indazole-3-carboxylic acid With 1,1'-carbonyldiimidazole In N,N-dimethyl-formamide at 20℃; for 0.5h; Inert atmosphere; Stage #2: tert-butyl 2-amino-2-(hydroxyimino)ethylcarbamate In N,N-dimethyl-formamide at 20℃; for 18h; Inert atmosphere;	92%
Stage #1: 1H-Indazole-3-carboxylic acid With 1,1'-carbonyldiimidazole In N,N-dimethyl-formamide at 20℃; for 0.5h; Inert atmosphere; Stage #2: tert-butyl 2-amino-2-(hydroxyimino)ethylcarbamate In N,N-dimethyl-formamide at 20℃;	92%

1H-Indazole-3-carboxylic acid (4498-67-3) → 1H-indazole-3-carbonyl chloride (72083-74-0)

Conditions	Yield
With thionyl chloride at 20℃; for 2h; Inert atmosphere;	91%
With thionyl chloride for 1h; Reflux;
With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane for 2h;
With thionyl chloride for 8h; Reflux;
With thionyl chloride at 80℃; for 4h;

1H-Indazole-3-carboxylic acid (4498-67-3) + dimethyl sulfate (77-78-1) → 1-methylindazole-3-carboxylic acid hydrochloride

Conditions	Yield
Stage #1: 1H-Indazole-3-carboxylic acid With calcium methylate In methanol for 2h; Heating / reflux; Stage #2: dimethyl sulfate In methanol for 3h; Heating / reflux; Stage #3: With hydrogenchloride In water for 2h; pH=1;	87.7%

1H-Indazole-3-carboxylic acid (4498-67-3) → 5-bromobenzopyrazole-3-carboxylic acid (1077-94-7)

Conditions	Yield
With bromine; acetic acid at 90 - 120℃; for 16h;	87.5%
Stage #1: 1H-Indazole-3-carboxylic acid With acetic acid at 120℃; Stage #2: With bromine; acetic acid at 90℃; for 16h;	87.5%
With bromine; acetic acid at 90 - 120℃; for 16h;	87.5%

1H-Indazole-3-carboxylic acid (4498-67-3) + dimethyl sulfate (77-78-1) → 1-methyl-1H-indazole-3-carboxylic acid (50890-83-0)

Conditions	Yield
Stage #1: 1H-Indazole-3-carboxylic acid With calcium oxide In methanol for 2h; Heating / reflux; Stage #2: dimethyl sulfate In methanol for 4h; Heating / reflux;	85.6%
Stage #1: 1H-Indazole-3-carboxylic acid With magnesium n-propylate In propan-1-ol for 2h; Heating / reflux; Stage #2: dimethyl sulfate In propan-1-ol at 20℃; for 5h; Heating / reflux;	83.8%
Stage #1: 1H-Indazole-3-carboxylic acid With magnesium ethylate In propan-1-ol for 2h; Heating / reflux; Stage #2: dimethyl sulfate In propan-1-ol at 20℃; for 2h; Heating / reflux;	79.2%
Stage #1: 1H-Indazole-3-carboxylic acid With barium(II) oxide In propan-1-ol for 2h; Heating / reflux; Stage #2: dimethyl sulfate In propan-1-ol at 20℃; for 2h; Heating / reflux;	65.4%

4-amino-1-benzylpiperidine (50541-93-0) + 1H-Indazole-3-carboxylic acid (4498-67-3) → N-(1-benzylpiperidin-4-yl)-1H-indazole-3-carboxamide (207296-87-5)

Conditions	Yield
Stage #1: 1H-Indazole-3-carboxylic acid With 1,1'-carbonyldiimidazole In DMF (N,N-dimethyl-formamide) at 60℃; for 2h; Stage #2: 4-amino-1-benzylpiperidine In DMF (N,N-dimethyl-formamide) at 60℃; for 2h;	85.1%
With 1,1'-carbonyldiimidazole 1.) DMF, 60 deg C, 2 h, 2.) DMF, 60 deg C, 2 h; Yield given. Multistep reaction;
In N-methyl-acetamide; dichloromethane; 1,1'-carbonyldiimidazole	76%.

N,O-dimethylhydroxylamine*hydrochloride (6638-79-5) + 1H-Indazole-3-carboxylic acid (4498-67-3) → 1H-indazole-3-carboxylic acid methoxy(methyl)amide (351457-12-0)

Conditions	Yield
Stage #1: N,O-dimethylhydroxylamine*hydrochloride; 1H-Indazole-3-carboxylic acid With pyridine In tetrahydrofuran at 20℃; for 3h; Cooling with ice; Stage #2: With pyridine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In tetrahydrofuran at 20℃;	85%
With pyridine; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In tetrahydrofuran at 0 - 20℃; for 13.5h;	84%
Stage #1: N,O-dimethylhydroxylamine*hydrochloride; 1H-Indazole-3-carboxylic acid With pyridine In tetrahydrofuran at 0 - 20℃; for 2.5h; Stage #2: With pyridine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In tetrahydrofuran at 20℃;	84%

1H-Indazole-3-carboxylic acid (4498-67-3) → methyl 1H-indazole-3-carboxylate (43120-28-1)

Conditions	Yield
Stage #1: methanol With acetyl chloride at 0℃; for 0.166667h; Stage #2: 1H-Indazole-3-carboxylic acid at 0 - 20℃;	85%
With sodium bicarbonate; sulfuric acid In methanol	61%
In methanol

oxotribromobis(triphenylphosphine)rhenium(V) (18703-07-6, 74741-94-9, 162117-95-5) + 1H-Indazole-3-carboxylic acid (4498-67-3) → [ReO(bromide)2(indazole-3-carboxylate)(triphenylphosphine)]*(triphenylphosphine oxide)

Conditions	Yield
With air In tetrahydrofuran byproducts: HBr, P(C6H5)3; addn. of Re complex to N compd. (1:1) in C4H8O, heating under reflux for4 h; concn., cooling to room temp., slow diffusion of diethyl ether, isolation of crystals, elem. anal.;	85%

1H-Indazole-3-carboxylic acid (4498-67-3) → 1H-indazole-3-carboxamide (90004-04-9)

Conditions	Yield
Stage #1: 1H-Indazole-3-carboxylic acid With 4-methyl-morpholine; isobutyl chloroformate In tetrahydrofuran at -20℃; for 2h; Inert atmosphere; Stage #2: With ammonia In tetrahydrofuran; water at 20℃; for 1h;	85%
Stage #1: 1H-Indazole-3-carboxylic acid With 4-methyl-morpholine; isobutyl chloroformate In tetrahydrofuran at -20℃; for 2h; Inert atmosphere; Stage #2: With ammonia In tetrahydrofuran; water at 20℃; for 1h; Inert atmosphere;	85%
Stage #1: 1H-Indazole-3-carboxylic acid With thionyl chloride for 3h; Inert atmosphere; Reflux; Stage #2: With ammonia In tetrahydrofuran; water at 20℃; for 0.5h; Inert atmosphere;	76%

1H-Indazole-3-carboxylic acid (4498-67-3) + methyl iodide (74-88-4) → 1-methyl-1H-indazole-3-carboxylic acid (50890-83-0)

Conditions	Yield
Stage #1: 1H-Indazole-3-carboxylic acid With calcium oxide In methanol for 2h; Heating / reflux; Stage #2: methyl iodide In methanol at 20℃; for 26h; Heating / reflux;	83.8%
With hydrogenchloride; sodium chloride; sodium hydrogencarbonate In dimethyl sulfoxide; mineral oil

2-methoxy-phenylamine (90-04-0) + 1H-Indazole-3-carboxylic acid (4498-67-3) → N-(2-methoxyphenyl)-1H-indazole-3-carboxamide (23707-04-2)

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 100℃; for 10h;	82%
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 100℃;	70%

1H-Indazole-3-carboxylic acid (4498-67-3) + 4-amino-5-(4-methoxyphenyl)-4H-1,2,4-triazole-3-thiol (36209-49-1) → 3-[3-(4-methoxyphenyl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-6-yl]-1H-indazole

Conditions	Yield
With trichlorophosphate at 90 - 95℃;	82%

aniline (62-53-3) + 1H-Indazole-3-carboxylic acid (4498-67-3) → 1H-indazole-3-carboxylic acid phenylamide (23706-99-2)

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 100℃;	81%
Stage #1: 1H-Indazole-3-carboxylic acid With thionyl chloride for 3h; Inert atmosphere; Reflux; Stage #2: aniline In tetrahydrofuran at 20℃; for 0.5h; Inert atmosphere;	70%
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃; for 48h;	64%
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 100℃; for 10h;	59%

1H-Indazole-3-carboxylic acid (4498-67-3) + (±)-(1R,3r,5S)-9-benzyl-9-azabicyclo[3.3.1]nonan-3-yl acetate (76272-58-7) → N-[(3-endo)-9-(phenylmethyl)-9-azabicyclo[3.3.1]non-3-yl]-1H-indazole-3-carboxamide (1210745-16-6)

Conditions	Yield
Stage #1: 1H-Indazole-3-carboxylic acid With benzotriazol-1-ol; dicyclohexyl-carbodiimide In dichloromethane; N,N-dimethyl-formamide at 20℃; for 2h; Stage #2: (±)-(1R,3r,5S)-9-benzyl-9-azabicyclo[3.3.1]nonan-3-yl acetate In dichloromethane; N,N-dimethyl-formamide at 20℃; Inert atmosphere;	81%

Upstream product

• 78155-12-1 ethyl 1-acetyl-1H-indazole-3-carboxylate 
• 52328-68-4 ethyl 1-(4-nitrophenyl)-1H-indazole-3-carboxylate 
• 42366-35-8 hydroxyimino-N-phenylacetamide 
• 62-53-3 aniline 
• 64132-13-4 3-(hydroxymethyl)-1H-indazole 
• 99233-20-2 α-hydroxy-2-bromoacetophenone 
• 2142-69-0 2-bromophenyl methyl ketone 
• 1630015-70-1 4-bromobenzylideneaminoisatine 
• 16917-42-3 4-bromobenzaldehyde phenylhydrazone 
• 109411-83-8 oxalic acid-(benzylidene-phenyl-hydrazide)-chloride 
• 10604-20-3 1-(benzylideneamino)indoline-2,3-dione 
• 588-64-7 benzaldehyde phenylhydrazone 
• 100-63-0 phenylhydrazine 
• 91-56-5 indole-2,3-dione 

Downstream Products

• 43120-28-1 methyl 1H-indazole-3-carboxylate 
• 109216-60-6 1-Methyl-1H-indazole-3-carboxylic acid methyl ester 
• 173600-14-1 1-isopropyl-1H-indazole-3-carboxylic acid 
• 174180-54-2 1-Benzyl-1H-indazole-3-carboxylic acid benzyl ester 
• 677305-02-1 Facinicline hydrochloride 
• 1079-47-6 methyl 5-iodo-1H-indazole-3-carboxylate 
• 882188-87-6 tert-butyl 3-(hydroxymethyl)-1H-indazole-1-carboxylate 
• 78155-74-5 5-bromo-1H-indazole-3-carboxylic acid methyl ester 
• 936132-62-6 3-(2-benzyloxycarbonylamino-2-methoxycarbonyl-vinyl)-5-bromo-indazole-1-carboxylic acid tert-butyl ester 
• 936132-64-8 3-(2-benzyloxycarbonylamino-2-methoxycarbonyl-vinyl)-indazole-1-carboxylic acid tert-butyl ester 
• 936132-61-5 5-bromo-3-formyl-indazole-1-carboxylic acid tert-butyl ester 
• 882188-88-7 tert-butyl 3-formyl-1H-indazole-1-carboxylate 
• 5235-10-9 1H-indazole-3-carboxaldehyde 
• 59591-73-0 (1H-indazol-3-yl)(phenyl)methanone 

Relevant articles and documents

Electrochemical dehydrogenative C-N coupling of hydrazones for the synthesis of 1H-indazoles

An electrochemical dehydrogenative C-N coupling method has been developed for the synthesis of 1H-indazoles from easily available hydrazones. Various functional groups are compatible with this metal- and oxidant-free protocol which can be carried out on a gram-scale under neutral and mild conditions. This method was applied for the efficient synthesis of anti-tumor compounds. Mechanism studies show that HFIP plays an important role in this transformation which might involve a radical pathway.

Indazole compounds and preparation method and application thereof

The invention provides indazole compounds and a preparation method and application thereof. A series of completely new small molecule PI3Kdelta inhibitors are designed and synthesized by using indazole as a structural mother nucleus, the PI3Kdelta kinase inhibitory activity test and MV-4-11 cell activity test of the compounds are carried out, and the indazole compounds exhibit better kinase subtype selectivity, and exhibit better in vitro proliferation inhibitory activity against tumor cell lines. The compounds can be used in the preparation of antitumor drugs and in the preparation of activedrugs for inhibiting PI3Kdelta kinase, and a new way is provided for the antitumor drug research. The raw materials are cheap and easy to obtain, the preparation method is simple, and the large-scaleproduction is suitable. The structural formula is as shown in the specification.

Copper(I) Oxide-Mediated Cyclization of o-Haloaryl N-Tosylhydrazones: Efficient Synthesis of Indazoles

An efficient synthesis of indazoles from readily accessible E/Z mixtures of o-haloaryl N-tosylhydrazones has been developed. The thermo-induced isomerization of N-tosylhydrazones is discussed. A series of valuable indazole derivatives are prepared in good yields, and the method has been successfully applied to the synthesis of the bioactive compounds, lonidamine, AF-2785, axitinib, YC-1 and YD-3.