50890-83-0

Basic information

• Product Name: 1-Methylindazole-3-carboxylic acid
• Synonyms: 1-Methylindazole-3-carbox...;Granisetron Related Compound D (15 mg) (1-methyl-1H-indazole-3-carboxylic acid);1-Methyl INDAZOLE 3,CARBOXILIC ACID;Methyl-1H-indazole-3-carboxyl;1-Methylindazole-3-carboxylicacid,97%;1-Methylindazole-3-carboxylic acid 97%;1-Methyl-1H-indazol-3-carboxylic acid;1-METHYLINDAZOLE-3-CARBOXYLIC ACID
• CAS NO: 50890-83-0
• Molecular Formula: C₉H₈N₂O₂
• Molecular Weight: 176.17
• EINECS: 1308068-626-2
• Product Categories: Intermediates & Fine Chemicals;Pharmaceuticals;Heterocycles, Impurities, Indole Derivatives, Pharmaceuticals, Intermediates & Fine Chemicals;Acids and Derivatives;Heterocycles;Indoles and derivatives;pharmacetical;Carboxylic Acids;Benzene derivates;Organic acids;(intermediate of granisetron);Carboxylic Acids;Fused Ring Systems;Building Blocks;Heterocyclic Building Blocks;Indazoles;Impurities;Indole Derivatives
• Mol File: 50890-83-0.mol
• Article Data: 8

Chemical Properties

• Melting Point: 213 °C
• Boiling Point: 383.7 °C at 760 mmHg
• Flash Point: 185.8 °C
• Appearance: White to light yellow needle crystal
• Density: 1.35 g/cm³
• Vapor Pressure: 1.42E-06mmHg at 25°C
• Refractive Index: 1.653
• Storage Temp.: Refrigerator
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 3.14±0.10(Predicted)
• Water Solubility: Insoluble in water. Soluble in DMSO and Methanol.
• CAS DataBase Reference: 1-Methylindazole-3-carboxylic acid(CAS DataBase Reference)
• NIST Chemistry Reference: 1-Methylindazole-3-carboxylic acid(50890-83-0)
• EPA Substance Registry System: 1-Methylindazole-3-carboxylic acid(50890-83-0)

Safety Data

• Hazard Codes: Xn
• Statements: 22-36-36/37/38
• Safety Statements: 26-36/37/39-22
• WGK Germany: 3
• HazardClass: IRRITANT
• Hazardous Substances Data: 50890-83-0(Hazardous Substances Data)

Usage

Chemical Properties

Off White Solid

Uses

Different sources of media describe the Uses of 50890-83-0 differently. You can refer to the following data:
1. Granisetron Impurity D.
2. 1-Methylindazole-3-carboxylic acid is used as important raw material and intermediate used in organic Synthesis, pharmaceuticals, agrochemicals and dyestuff. It is also used as a pharmaceutical adjuvant, Granisetron Impurity D.

Synthesis Reference(s)

The Journal of Organic Chemistry, 63, p. 8448, 1998 DOI: 10.1021/jo981557o

InChI:InChI=1/C9H8N2O2/c1-11-7-5-3-2-4-6(7)8(10-11)9(12)13/h2-5H,1H3,(H,12,13)

Synthetic route

1-Methyl-1H-indazole-3-carboxylic acid methyl ester (109216-60-6) → 1-methyl-1H-indazole-3-carboxylic acid (50890-83-0)

Conditions	Yield
With sodium hydroxide In tetrahydrofuran Ambient temperature;	100%
With sodium hydroxide In tetrahydrofuran at 20℃; for 18h;	90%
With hydrogenchloride; sodium hydroxide In tetrahydrofuran	68%

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%

methyl 2-(2-iodophenyl)-2-(2-methylhydrazono)acetate → 1-methyl-1H-indazole-3-carboxylic acid (50890-83-0)

Conditions	Yield
Stage #1: methyl 2-(2-iodophenyl)-2-(2-methylhydrazono)acetate With copper(l) iodide; caesium carbonate; L-proline In dimethyl sulfoxide at 95 - 100℃; for 7h; Stage #2: With hydrogenchloride In water; toluene pH=2 - 2.5;	84%

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

methyl 2-(2-chlorophenyl)-2-(2-methylhydrazono)acetate → 1-methyl-1H-indazole-3-carboxylic acid (50890-83-0)

Conditions	Yield
Stage #1: methyl 2-(2-chlorophenyl)-2-(2-methylhydrazono)acetate With copper(l) iodide; caesium carbonate; L-proline In dimethyl sulfoxide at 95 - 100℃; for 7h; Stage #2: With hydrogenchloride In water; toluene pH=2 - 2.5;	83%

Methyl 2-(2-bromophenyl)-2-(2-methylhydrazono)acetate → 1-methyl-1H-indazole-3-carboxylic acid (50890-83-0)

Conditions	Yield
Stage #1: Methyl 2-(2-bromophenyl)-2-(2-methylhydrazono)acetate With copper(l) iodide; caesium carbonate; L-proline In dimethyl sulfoxide at 95 - 100℃; for 7h; Stage #2: With hydrogenchloride In water; toluene pH=2 - 2.5;	81%

trimethyl phosphite (512-56-1) + 1H-Indazole-3-carboxylic acid (4498-67-3) → 1-methyl-1H-indazole-3-carboxylic acid (50890-83-0)

Conditions	Yield
Stage #1: 1H-Indazole-3-carboxylic acid With magnesium ethylate In propan-1-ol for 2h; Heating / reflux; Stage #2: trimethyl phosphite In propan-1-ol at 20℃; for 7h; Heating / reflux;	78.3%

1-methyl-1H-indazole-3-carbonitrile (31748-44-4) → 1-methyl-1H-indazole-3-carboxylic acid (50890-83-0)

Conditions	Yield
With hydrogenchloride

methyl iodide (74-88-4) + ethyl 1H-indazole-3-carboxylate (4498-68-4) → 1-methyl-1H-indazole-3-carboxylic acid (50890-83-0)

Conditions	Yield
With sodium methylate Der Methylester entsteht beim nachfolgenden Verseifen und Verestern mit Methanol und konz. Schwefelsaeure und dann man verseift ihn waessr-methylalkoh. Kalilauge;
With sodium methylate und verseifen des entstandenen Esters mit waessr.-methylalkoh. Kalilauge;

1-methyl-indazole-carboxylic acid-(3)-methyl ester → 1-methyl-1H-indazole-3-carboxylic acid (50890-83-0)

Conditions	Yield
With potassium hydroxide und verseifen des entstandenen Esters mit waessr.-methylalkoh. Kalilauge;

indazole-3-carbonitrile (50264-88-5) → 1-methyl-1H-indazole-3-carboxylic acid (50890-83-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: aq. NaOH solution 2: aqueous HCl View Scheme
Multi-step reaction with 2 steps 1: 150 °C 2: aqueous HCl View Scheme

2-(2-bromophenyl)-2-oxoacetamide → 1-methyl-1H-indazole-3-carboxylic acid (50890-83-0)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: thionyl chloride / 4.5 h / 40 - 64 °C 2.1: potassium carbonate / isopropyl alcohol / 6 h / 60 - 65 °C 3.1: L-proline; caesium carbonate; copper(l) iodide / dimethyl sulfoxide / 7 h / 95 - 100 °C 3.2: pH 2 - 2.5 View Scheme

2-bromobenzoic-acid (88-65-3) → 1-methyl-1H-indazole-3-carboxylic acid (50890-83-0)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: thionyl chloride 2.1: water; sodium chloride; sulfuric acid / 1.5 h / 40 - 45 °C 3.1: thionyl chloride / 4.5 h / 40 - 64 °C 4.1: potassium carbonate / isopropyl alcohol / 6 h / 60 - 65 °C 5.1: L-proline; caesium carbonate; copper(l) iodide / dimethyl sulfoxide / 7 h / 95 - 100 °C 5.2: pH 2 - 2.5 View Scheme

2-bromobenzoyl cyanide (88562-26-9) → 1-methyl-1H-indazole-3-carboxylic acid (50890-83-0)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: water; sodium chloride; sulfuric acid / 1.5 h / 40 - 45 °C 2.1: thionyl chloride / 4.5 h / 40 - 64 °C 3.1: potassium carbonate / isopropyl alcohol / 6 h / 60 - 65 °C 4.1: L-proline; caesium carbonate; copper(l) iodide / dimethyl sulfoxide / 7 h / 95 - 100 °C 4.2: pH 2 - 2.5 View Scheme

2-(2-iodophenyl)-2-oxoacetamide → 1-methyl-1H-indazole-3-carboxylic acid (50890-83-0)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: thionyl chloride / 4.5 h / 40 - 64 °C 2.1: potassium carbonate / isopropyl alcohol / 6 h / 60 - 65 °C 3.1: L-proline; caesium carbonate; copper(l) iodide / dimethyl sulfoxide / 7 h / 95 - 100 °C 3.2: pH 2 - 2.5 View Scheme

2-Iodobenzoic acid (88-67-5) → 1-methyl-1H-indazole-3-carboxylic acid (50890-83-0)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: thionyl chloride 2.1: water; sodium chloride; sulfuric acid / 1.5 h / 40 - 45 °C 3.1: thionyl chloride / 4.5 h / 40 - 64 °C 4.1: potassium carbonate / isopropyl alcohol / 6 h / 60 - 65 °C 5.1: L-proline; caesium carbonate; copper(l) iodide / dimethyl sulfoxide / 7 h / 95 - 100 °C 5.2: pH 2 - 2.5 View Scheme

2-iodobenzoyl cyanide → 1-methyl-1H-indazole-3-carboxylic acid (50890-83-0)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: water; sodium chloride; sulfuric acid / 1.5 h / 40 - 45 °C 2.1: thionyl chloride / 4.5 h / 40 - 64 °C 3.1: potassium carbonate / isopropyl alcohol / 6 h / 60 - 65 °C 4.1: L-proline; caesium carbonate; copper(l) iodide / dimethyl sulfoxide / 7 h / 95 - 100 °C 4.2: pH 2 - 2.5 View Scheme

2-(2-chlorophenyl)-2-oxoacetamide → 1-methyl-1H-indazole-3-carboxylic acid (50890-83-0)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: thionyl chloride / 4.5 h / 40 - 64 °C 2.1: potassium carbonate / isopropyl alcohol / 6 h / 60 - 65 °C 3.1: L-proline; caesium carbonate; copper(l) iodide / dimethyl sulfoxide / 7 h / 95 - 100 °C 3.2: pH 2 - 2.5 View Scheme

ortho-chlorobenzoic acid (118-91-2) → 1-methyl-1H-indazole-3-carboxylic acid (50890-83-0)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: thionyl chloride 2.1: water; sodium chloride; sulfuric acid / 1.5 h / 40 - 45 °C 3.1: thionyl chloride / 4.5 h / 40 - 64 °C 4.1: potassium carbonate / isopropyl alcohol / 6 h / 60 - 65 °C 5.1: L-proline; caesium carbonate; copper(l) iodide / dimethyl sulfoxide / 7 h / 95 - 100 °C 5.2: pH 2 - 2.5 View Scheme

2-chlorobenzoyl cyanide (35022-42-5) → 1-methyl-1H-indazole-3-carboxylic acid (50890-83-0)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: water; sodium chloride; sulfuric acid / 1.5 h / 40 - 45 °C 2.1: thionyl chloride / 4.5 h / 40 - 64 °C 3.1: potassium carbonate / isopropyl alcohol / 6 h / 60 - 65 °C 4.1: L-proline; caesium carbonate; copper(l) iodide / dimethyl sulfoxide / 7 h / 95 - 100 °C 4.2: pH 2 - 2.5 View Scheme

methyl 2-chlorobenzoylformate (34966-49-9) → 1-methyl-1H-indazole-3-carboxylic acid (50890-83-0)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: potassium carbonate / isopropyl alcohol / 6 h / 60 - 65 °C 2.1: L-proline; caesium carbonate; copper(l) iodide / dimethyl sulfoxide / 7 h / 95 - 100 °C 2.2: pH 2 - 2.5 View Scheme

(2-bromophenyl)-oxoacetic acid methyl ester (122394-38-1) → 1-methyl-1H-indazole-3-carboxylic acid (50890-83-0)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: potassium carbonate / isopropyl alcohol / 6 h / 60 - 65 °C 2.1: L-proline; caesium carbonate; copper(l) iodide / dimethyl sulfoxide / 7 h / 95 - 100 °C 2.2: pH 2 - 2.5 View Scheme

(2-iodophenyl)-oxoacetic acid methyl ester → 1-methyl-1H-indazole-3-carboxylic acid (50890-83-0)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: potassium carbonate / isopropyl alcohol / 6 h / 60 - 65 °C 2.1: L-proline; caesium carbonate; copper(l) iodide / dimethyl sulfoxide / 7 h / 95 - 100 °C 2.2: pH 2 - 2.5 View Scheme

1H-Indazole-3-carboxylic acid (4498-67-3) → 1-methyl-1H-indazole-3-carboxylic acid (50890-83-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: thionyl chloride / 3 h / Reflux 2: N,N-dimethyl-formamide / 2 h / 60 °C 3: sodium hydroxide / tetrahydrofuran / 18 h / 20 °C View Scheme

methyl 1H-indazole-3-carboxylate (43120-28-1) → 1-methyl-1H-indazole-3-carboxylic acid (50890-83-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: N,N-dimethyl-formamide / 2 h / 60 °C 2: sodium hydroxide / tetrahydrofuran / 18 h / 20 °C View Scheme

1-methyl-1H-indazole-3-carboxylic acid (50890-83-0) → 1-methylindazole-3-carboxylic acid chloride (106649-02-9)

Conditions	Yield
With thionyl chloride	100%
With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane for 1h;
With thionyl chloride In chloroform Heating;

1-methyl-1H-indazole-3-carboxylic acid (50890-83-0) + N-(methyl)-N-(p-toluenesulfonyl)ethynylamine (1005500-75-3) → 1-((N,4-dimethylphenyl)sulfonamido)vinyl 1-methyl-1H-indazole-3-carboxylate

Conditions	Yield
In dichloromethane at 25℃; for 4h;	99%
In chloroform at 20℃; for 5h;	99%

1-methyl-1H-indazole-3-carboxylic acid (50890-83-0) + 2-allylphenol (695-84-1) → 2,3-dihydrobenzofuran-3-yl 1-methyl-1H-indazole-3-carboxylate

Conditions	Yield
With tert.-butylhydroperoxide; tetra-(n-butyl)ammonium iodide In water; 1,2-dichloro-ethane at 60℃; for 6h;	98%
With tert.-butylhydroperoxide; tetra-(n-butyl)ammonium iodide In 1,2-dichloro-ethane at 60℃; for 6h;	93%

1-methyl-1H-indazole-3-carboxylic acid (50890-83-0) + cyclohexene (110-83-8) → cyclohex-2-enyl 1-methyl-1H-indazole-3-carboxylate (1383677-55-1)

Conditions	Yield
With tert.-butylhydroperoxide; tetra-(n-butyl)ammonium iodide In benzene at 80℃; for 8h;	93%

oxalyl dichloride (79-37-8) + 1-methyl-1H-indazole-3-carboxylic acid (50890-83-0) + ethyl acetate n-hexane + methyl 4-amino-3-chlorobenzene-1-acetate (101349-30-8) → [3-chloro-4-[(1-methyl-3-indazolylcarbonyl)amino]phenyl]acetic acid methyl ester

Conditions	Yield
With triethylamine In dichloromethane; water; N,N-dimethyl-formamide	89%

1-methyl-1H-indazole-3-carboxylic acid (50890-83-0) → 1-methyl-1H-indazole-3-carbohydrazide (90558-67-1)

Conditions	Yield
With hydrazine hydrate; acetic acid Reflux;	89%
Multi-step reaction with 2 steps 1: sulfuric acid / 10 h / Reflux 2: hydrazine hydrate / ethanol / 6 h / Reflux View Scheme

methanol (67-56-1) + 1-methyl-1H-indazole-3-carboxylic acid (50890-83-0) → 1-Methyl-1H-indazole-3-carboxylic acid methyl ester (109216-60-6)

Conditions	Yield
With sulfuric acid for 4h; Reflux;	85%

1-methyl-1H-indazole-3-carboxylic acid (50890-83-0) → C9H9N3O

Conditions	Yield
With 1,1'-carbonyldiimidazole In tetrahydrofuran at 20℃; for 1.5h;	83%
Stage #1: 1-methyl-1H-indazole-3-carboxylic acid With 1,1'-carbonyldiimidazole In tetrahydrofuran at 20℃; for 1.5h; Stage #2: With ammonium hydroxide In tetrahydrofuran; water for 0.25h;	83%
Stage #1: 1-methyl-1H-indazole-3-carboxylic acid With 1,1'-carbonyldiimidazole In tetrahydrofuran at 20℃; for 1.5h; Stage #2: With ammonium hydroxide In tetrahydrofuran; water for 0.25h;	83%
Stage #1: 1-methyl-1H-indazole-3-carboxylic acid With 1,1'-carbonyldiimidazole In tetrahydrofuran at 20℃; for 1.5h; Stage #2: With ammonium hydroxide In tetrahydrofuran; water for 0.25h;	83%

1-methyl-1H-indazole-3-carboxylic acid (50890-83-0) + aniline (62-53-3) → 1-methyl-N-phenyl-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℃; for 10h;	83%

1-methyl-1H-indazole-3-carboxylic acid (50890-83-0) + {2‐azabicyclo[2.1.1]hexan‐1‐yl}methanamine → N‐({2‐benzyl‐2‐azabicyclo[2.1.1]hexan‐1‐yl}methyl)‐1‐methyl‐1H‐indazole‐3‐carboxamide

Conditions	Yield
Stage #1: 1-methyl-1H-indazole-3-carboxylic acid With 1-[(1-(cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylamino-morpholino)]-uronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 0.5h; Stage #2: {2‐azabicyclo[2.1.1]hexan‐1‐yl}methanamine In dichloromethane at 20℃; for 1h;	82%

1-methyl-1H-indazole-3-carboxylic acid (50890-83-0) + endo-9-methyl-9-azabicyclo[3.3.1]nonan-3-amine (76272-41-8, 141650-55-7, 76272-56-5) → granisetron (109889-09-0, 124998-65-8)

Conditions	Yield
With 4-(2-(1,3-dioxa-3a1,8,10-triaza-2,3a,14b-triboradibenzo[fg,op]tetracen-2-yl)phenyl)benzo[c]pyrimido[4,5-e][1,2]azaborinin-6(5H)-ol In toluene at 85℃; for 16h; Molecular sieve;	81%
With tris(2,2,2-trifluoroethyl) borate for 72h; Dean-Stark; Reflux;	45%

1-methyl-1H-indazole-3-carboxylic acid (50890-83-0) + cyanoacetic acid (372-09-8) → C12H10N2O2

Conditions	Yield
With tert.-butylhydroperoxide; sodium acetate; tetra-(n-butyl)ammonium iodide In tetrahydrofuran; water at 80℃; for 12h;	80%

1-methyl-1H-indazole-3-carboxylic acid (50890-83-0) + N,O-dimethylhydroxylamine*hydrochloride (6638-79-5) → 1-methyl-1H-indazole-3-carboxylic acid methoxy-methyl-amide

Conditions	Yield
With pyridine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In tetrahydrofuran at 0 - 20℃;	79%

tert.-butylhydroperoxide (75-91-2) + 1-methyl-1H-indazole-3-carboxylic acid (50890-83-0) → 1-Methyl-1H-indazole-3-carboxylic acid methyl ester (109216-60-6)

Conditions	Yield
With copper quinolate In water; dimethyl sulfoxide at 120℃; for 24h;	77%

1-methyl-1H-indazole-3-carboxylic acid (50890-83-0) + Pd(κ1-O-OAc)2(H2O)(κ1-C-((2,6-di-iso-propylphenyl)2(C3H2N2)) → (IPr)Pd(1-methyl-1H-indazole-3-carboxylate)(OAc)

Conditions	Yield
With potassium carbonate In tetrahydrofuran at 50℃; for 12h;	77%

1-methyl-1H-indazole-3-carboxylic acid (50890-83-0) + 6-amino-1,2-benzoxathiine 2,2-dioxide (1383813-19-1) → N-(2,2-dioxidobenzo[e][1,2]oxathiin-6-yl)-1-methyl-1H-indazole-3-carboxamide

Conditions	Yield
Stage #1: 1-methyl-1H-indazole-3-carboxylic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃; for 0.5h; Stage #2: 6-amino-1,2-benzoxathiine 2,2-dioxide In N,N-dimethyl-formamide at 20℃; for 16h;	76%

1-methyl-1H-indazole-3-carboxylic acid (50890-83-0) + 4-((aR)-6-aminospiro[3.3]heptan-2-yl)phthalazin-1-(2H)-one trifluoroacetate → 1-methyl-N-[(aR)-6-(4-oxo-3,4-dihydrophthalazin-1-yl)spiro[3.3]heptan-2-yl]-1H-indazole-3-carboxamide

Conditions	Yield
Stage #1: 1-methyl-1H-indazole-3-carboxylic acid; 4-((aR)-6-aminospiro[3.3]heptan-2-yl)phthalazin-1-(2H)-one trifluoroacetate With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 0.0833333h; Stage #2: With HATU In N,N-dimethyl-formamide at 20℃; for 2h;	75%

1-methyl-1H-indazole-3-carboxylic acid (50890-83-0) + [(SIPr)Pd(OAc)2C(H2O)] → C38H48N4O4Pd

Conditions	Yield
With potassium carbonate In tetrahydrofuran at 50℃; for 12h;	72%

1-methyl-1H-indazole-3-carboxylic acid (50890-83-0) + 4-((aS)-6-aminospiro[3.3]heptan-2-yl)phthalazin-1(2H)-one trifluoroacetate → 1-methyl-N-[(aS)-6-(4-oxo-3,4-dihydrophthalazin-1-yl)spiro[3.3]heptan-2-yl]-1H-indazole-3-carboxamide

Conditions	Yield
Stage #1: 1-methyl-1H-indazole-3-carboxylic acid; 4-((aS)-6-aminospiro[3.3]heptan-2-yl)phthalazin-1(2H)-one trifluoroacetate With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 0.0833333h; Stage #2: With HATU In N,N-dimethyl-formamide at 20℃; for 2h;	67%

ethyl 2-(4-amino-5-chloro-2-fluorophenyl)acetate (441717-78-8) + oxalyl dichloride (79-37-8) + 1-methyl-1H-indazole-3-carboxylic acid (50890-83-0) + ethyl acetate n-hexane → [5-chloro-2-fluoro-4-[(1-methyl-3-indazolylcarbonyl)amino]phenyl]acetic acid ethyl ester + (5-chloro-2-fluoro-4-((1-methyl-3-indazolylcarbonyl)amino)phenyl)acetic acid (441715-63-5)

Conditions	Yield
With triethylamine In N,N-dimethyl-formamide; benzene	A 63% B n/a

1-methyl-1H-indazole-3-carboxylic acid (50890-83-0) + cyanoacetic acid (372-09-8) → cyanomethyl 1-methyl-1H-indazole-3-carboxylate

Conditions	Yield
With tert.-butylhydroperoxide; sodium acetate; tetra-(n-butyl)ammonium iodide In tetrahydrofuran; water at 80℃; for 12h;	60%

1-methyl-1H-indazole-3-carboxylic acid (50890-83-0) → (1-methyl-1H-indazol-3-yl)methanol (1578-96-7)

Conditions	Yield
Stage #1: 1-methyl-1H-indazole-3-carboxylic acid With isobutyl chloroformate In tetrahydrofuran at -18℃; for 0.5h; Stage #2: With sodium tetrahydroborate; water In tetrahydrofuran for 1h;	54.31%

Upstream product

• 109216-60-6 1-Methyl-1H-indazole-3-carboxylic acid methyl ester 
• 4498-67-3 1H-Indazole-3-carboxylic acid 
• 77-78-1 dimethyl sulfate 
• 512-56-1 trimethyl phosphite 
• 43120-28-1 methyl 1H-indazole-3-carboxylate 
• 122394-38-1 (2-bromophenyl)-oxoacetic acid methyl ester 
• 34966-49-9 methyl 2-chlorobenzoylformate 
• 35022-42-5 2-chlorobenzoyl cyanide 
• 118-91-2 ortho-chlorobenzoic acid 
• 88-67-5 2-Iodobenzoic acid 
• 88562-26-9 2-bromobenzoyl cyanide 
• 88-65-3 2-bromobenzoic-acid 
• 74-88-4 methyl iodide 
• 50264-88-5 indazole-3-carbonitrile 

Downstream Products

• 441715-63-5 (5-chloro-2-fluoro-4-((1-methyl-3-indazolylcarbonyl)amino)phenyl)acetic acid 
• 109889-09-0 granisetron 

Relevant articles and documents

Sulfocoumarin-, Coumarin-, 4-Sulfamoylphenyl-Bearing Indazole-3-carboxamide Hybrids: Synthesis and Selective Inhibition of Tumor-Associated Carbonic Anhydrase Isozymes IX and XII

A series of sulfocoumarin-, coumarin-, and 4-sulfamoylphenyl-bearing indazole-3-carboxamide hybrids were synthesized and investigated as inhibitors of the human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms I and II (cytosolic isozymes), as well as hCA IX and XII (transmembrane, tumor-associated enzymes). Compounds 6 a–g (amide derivatives) and 7 a–h (triazoles) act as “prodrugs”, and their hydrolysis products are the de facto CA inhibitors. These compounds displayed sub-micromolar to high-nanomolar inhibitory activity against hCA isoforms IX and XII, which were recently validated as antitumor drug targets. Moreover, no inhibition of the off-target hCA I and II isoforms was observed. Compounds 8 a–f (another set of triazoles) exhibited nanomolar inhibition against hCA isoforms I, II, IX and XII, among which compounds 8 c, 8 d, and 8 f were found to inhibit the tumor-associated hypoxia-induced hCA isoform IX with Ki values of 1.8, 2.3, and 2.0 nm respectively. Further exploration of these compounds could be useful for the development of novel antitumor agents with selective mechanisms of CA inhibitory action.

Process for preparing 1-methylindazole-3-carboxylic acid

A method of performing a bearer path assurance test across a packet-based IP network is provided. The method includes establishing a bearer path across the IP network and performing a bearer path assurance test during call setup before cutting through the call. The method can also include creating a timestamp at the originating office, sending the timestamp from the originating office to a terminating office, sending the timestamp from the terminating office to the originating office, receiving the timestamp at the originating office, and verifying the continuity of the bearer path. The method can also include evaluating round trip delay and packet loss using one or more timestamps.

Indazole derivatives having monocyclic amine

An indazole compound having the formula (I): wherein: R1 is hydrogen, C1 -C6 alkyl, C3 -C6 alkenyl or C3 -C6 cycloalkyl; Q is carbonyl, thiocarbonyl or methylene; and R2 is a group of the formula (II) or (IV); STR1 wherein R1 is C1 -C6 alkyl, C3 -C6 alkenyl or benzyl, of which a phenyl group thereof is optionally mono- or di-substituted by the same or different halogen or methoxy; m is 0 to 2; n and o is 1 or 2. The compound exhibits 5-HT4 receptor agonist activity.