677304-69-7

Basic information

• Product Name: 1H-INDAZOLE-7-CARBOXYLIC ACID
• Synonyms: 7-INDAZOLE CARBOXYLLIC ACID;1H-INDAZOLE-7-CARBOXYLIC ACID;7-INDAZOLE CARBOXYLIC ACID;7-Carboxy-1H-indazole;7-(1H)Indazole carboxylic acid;1H-Indazol-7-carboxylic acid
• CAS NO: 677304-69-7
• Molecular Formula: C₈H₆N₂O₂
• Molecular Weight: 162.15
• Product Categories: Building Blocks;Indazole;Amines;C8;Chemical Synthesis;New Products for Chemical Synthesis;Nitrogen Compounds;Organic Building Blocks;Indazoles
• Mol File: 677304-69-7.mol
• Article Data: 6

Chemical Properties

• Melting Point: ca 240℃
• Boiling Point: 443.7 °C at 760 mmHg
• Flash Point: 222.2 °C
• Appearance: White to yellow/Crystalline Powder
• Density: 1.506 g/cm³
• Storage Temp.: Sealed in dry,Room Temperature
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 3.71±0.10(Predicted)
• CAS DataBase Reference: 1H-INDAZOLE-7-CARBOXYLIC ACID(CAS DataBase Reference)
• NIST Chemistry Reference: 1H-INDAZOLE-7-CARBOXYLIC ACID(677304-69-7)
• EPA Substance Registry System: 1H-INDAZOLE-7-CARBOXYLIC ACID(677304-69-7)

Safety Data

• Hazardous Substances Data: 677304-69-7(Hazardous Substances Data)

Usage

Uses

1H-indazole-7-carboxylic Acid is an inhibitor of nitric oxide synthases.

Preparation

Synthesis of 1H-indazole-7-carboxylic acid, H2L4: To 60 mL anhydrous toluene under a nitrogen atmosphere was added methyl-2-amino-3-methylbenzoate (1.8 g, 11 mmol) and KOAc (560 mg, 5.7 mmol), and the mixture heated to reflux, at which time acetic anhydride (3.2 mL, 34 mmol) was added and the mixture stirred at reflux for 10 min. Isoamyl nitrite (2.3 mL, 18 mmol) was added over 30 min and the mixture refluxed overnight. On cooling, the mixture was filtered and evaporated to dryness to give 1.6 g of a pale brown solid, which analysed for methyl 1H-indazole-7-carboxylate. This material was taken up in 40 mL THF, added to a solution of LiOH (5 g, 210 mmol) in 40 mL water, and heated at reflux for 48 h. On cooling, the mixture was concentrated on a rotary evaporator and the resulting aqueous phase filtered and adjusted to pH 4 with dilute HCl, to precipitate the product, which was filtered, washed with water and dried under vacuum. Yield 810 mg, 45%; mp 218–222 °C (decomp); δH (500 MHz, d6-DMSO): 7.23 (t, 1H, J = 7.5 Hz, H4 ), 7.97 (dd, 1H, J = 7.5, 1.0 Hz, H3 ), 8.06 (dd, 1H, J = 7.8, 0.8 Hz, H5 ), 8.21 (s, 1H, H2 ), 13.1 (br s, 2H, H1 & H6 ); δc (125 MHz, d6-DMSO): 113.7, 120.1, 124.6, 126.5, 129.0, 134.3, 138.0, 167.0; HRMS-ESI m/z: found: 163.0503; C8H7N2O2 requires: 163.0502 [M + H+ ]; ˉνmax/cm?1 (KBr): 3316 s br, 1700 s, 1619 m, 1592 m, 1509 m, 1285 s, 1201 m, 1145 m, 1078 m, 1056 w, 943 m, 858 s, 745 s, 638 m, 601 m.

Upstream product

• 22223-49-0 methyl 2-amino-3-methylbenzoate 
• 37619-23-1 2-acetylamino-3-methyl-benzoic acid methyl ester 
• 4389-45-1 3-methylantranilic acid 
• 256228-64-5 1H-indazole-7-carbonitrile 
• 677304-71-1 methyl 1H-indazole-7-carboxylate hydrochloride 
• 755752-82-0 1H-indazole-7-carboxylic acid methyl ester 

Downstream Products

• 1031413-43-0 1'-(1H-indazol-7-ylcarbonyl)-6,7-dimethylspiro[chromene-2,4'-piperidin]-4(3H)-one 
• 952479-70-8 1H-indazole-7-carboxamide 
• 1031413-61-2 1'-(1H-indazol-7-ylcarbonyl)-6-methylspiro[chromene-2,4'-piperidin]-4(3H)-one 
• 1031413-79-2 1'-(1H-indazol-7-ylcarbonyl)-5-phenylspiro[chromene-2,4'-piperidin]-4(3H)-one 
• 755752-82-0 1H-indazole-7-carboxylic acid methyl ester 
• 944899-05-2 methyl 3-iodo-1H-indazole-7-carboxylic acid 
• 312746-72-8 1-H-indazole-7-carbaldehyde 
• 1092961-09-5 (1H-indazol-7-yl)methanol 
• 1476776-76-7 N‐tert‐butyl‐1H‐indazole‐7‐carboxamide 
• 1038915-73-9 2-[4-((3S)-3-piperidinyl)phenyl]-2H-indazole-7-carboxamide p-toluenesulfonic acid salt 

Relevant articles and documents

Discrete and polymeric Cu(ii) complexes featuring substituted indazole ligands: Their synthesis and structural chemistry

Reported here are the syntheses of four indazole-based ligands and the structural characterisation of four Cu(ii) complexes derived from them. The ligands 1-(2-pyridyl)-1H-indazole, L1, and 2-(2-pyridyl)-2H-indazole, L2, have been characterised by single crystal X-ray diffraction methods for the first time. The intramolecular structural changes within L1 and L2 that result from the transition from the 1H to the 2H electronic configuration have been delineated. The synthesis of 1H-indazole-6-carboxylic acid, H2L3, and 1H-indazole-7-carboxylic acid, H2L4, is fully described and the structure of H2L4·H2O determined. The structures of two discrete mononuclear complexes {[Cu(L1)2(NO3)]·NO3·1.5H2O}, 1, and {[Cu(L2)2(NO3)]·NO3}, 2, have been determined and their molecular compositions corroborated by solution-based methods. Reaction of Cu(ii) with H2L3 generates a 2D coordination polymer, [Cu3(HL3)4(NO3)2(EtOH)2]·3(C6H6)·2(H2O), 3, that features the archetypal [Cu2(OAc)4] paddlewheel motif and 1D channels; whereas reaction with H2L4 gives a discrete complex [Cu(HL4)2]·H2O·MeOH, 4, in which hydrogen bonding interactions link indazole dimers via a water molecule to yield a 1D network.

Inhibitory effects of a series of 7-substituted-indazoles toward nitric oxide synthases: Particular potency of 1H-indazole-7-carbonitrile

A series of new 7-monosubstituted and 3,7-disubstituted indazoles have been prepared and evaluated as inhibitors of nitric oxide synthases (NOS). 1H-Indazole-7-carbonitrile (6) was found equipotent to 7-nitro-1H-indazole (1) and demonstrated preference for constitutive NOS over inducible NOS. By contrast, 1H-indazole-7-carboxamide (8) was slightly less potent but demonstrated a surprising selectivity for the neuronal NOS. Further substitution of 6 by a Br-atom at carbon-3 of the heterocycle enhanced 10-fold the inhibitory effects. Inhibition of NO formation by 6 appeared to be competitive versus both substrate and the cofactor (6R)-5,6,7,8-tetrahydro-l-biopterin (H4B). In close analogies with 1, compound 6 strongly inhibited the NADPH oxidase activity of nNOS and induced a spin state transition of the heme-FeIII. Our results are explained with the help of the X-ray structures that identified key-features for binding of 1 at the active site of NOS.

Compounds

This invention relates to nicotinamide derivatives of general formula (I): in which R1, Z and R2 have the meanings defined herein, and to processes for the preparation of, intermediates used in the preparation of, compositions containing and the uses of such derivatives.