Methyl 1H-indazole-3-carboxylate
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Product Description
Methyl 1H-indazole-3-carboxylate is a versatile heterocyclic ester that serves as a pivotal building block in medicinal and synthetic chemistry. This white to off-white, organic-soluble solid is routinely employed as a key intermediate for constructing indazole-based pharmacophores, including anti-cancer and anti-inflammatory agents. Prepared from 1H-indazole-3-carboxylic acid, the ester undergoes straightforward N-alkylation, hydrolysis, chlorination, and subsequent amidation or esterification reactions to deliver diverse downstream products. Its utility is exemplified in the multi-step assembly of synthetic cannabinoids such as NPB-22 and Adamantyl-THPINACA, where methyl 1H-indazole-3-carboxylate functions as the common precursor that enables rapid exploration of structure–activity relationships across CB1 and CB2 receptor ligands.
Synthesis and Production
Methyl 1H-indazole-3-carboxylate is primarily used as a key synthetic intermediate.
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Role in Synthesis: As detailed in the research paper (s11419-023-00679-5.pdf), this compound is a fundamental starting material for the synthesis of more complex molecules, specifically synthetic cannabinoids.
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Synthetic Pathway: The synthesis of NPB-22, as described in the paper, begins with methyl 1H-indazole-3-carboxylate. The process involves:
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N-Alkylation: The compound is first N-alkylated using 1-bromopentane under basic conditions to introduce a pentyl chain onto the indazole nitrogen.
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Further Functionalization: The methyl ester group is then hydrolyzed, chlorinated, and finally esterified with 8-quinolinol to yield the final product, NPB-22.
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Commercial Availability: The PubChem record (COMPOUND_CID_657476.json) confirms it is a commercially available reagent, purchasable from various chemical suppliers (as indicated by the "Chemical Vendors" section). It was listed as being purchased from Accela ChemBio Co., Ltd. for the research in the paper.
Uses and Applications
The primary application of methyl 1H-indazole-3-carboxylate is in chemical research and pharmaceutical development.
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Building Block for Pharmaceuticals: Its main use is as a precursor or building block for the synthesis of biologically active compounds. The research paper explicitly demonstrates its use in creating the synthetic cannabinoid NPB-22.
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Privileged Scaffold: The indazole core is a "privileged scaffold" in medicinal chemistry, meaning it is a common structural motif found in molecules that interact with various biological targets. The ester group (-COOCH₃) is a versatile functional handle that can be readily converted into other groups (e.g., carboxylic acids, amides), allowing for the creation of a diverse library of derivatives for drug discovery.
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Research Chemical: It is used in academic and industrial research to study chemical reactions, develop new synthetic methodologies, and create novel compounds for biological testing.
Chemical and Physical Properties
Identifiers and Composition
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IUPAC Name: methyl 1H-indazole-3-carboxylate
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Molecular Formula: C₉H₈N₂O₂
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CAS Number: 43120-28-1
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Molar Mass: 176.17 g/mol
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Other Identifiers:
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EC Number: 694-545-7
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ChEBI ID: CHEBI:119835
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ChEMBL ID: CHEMBL1558246
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InChIKey: KWTCVAHCQGKXAZ-UHFFFAOYSA-N
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Canonical SMILES: COC(=O)C1=NNC2=CC=CC=C21
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Computed Physical and Chemical Properties (from PubChem)
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XLogP3: 1.7 (Indicates moderate lipophilicity)
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Hydrogen Bond Donor Count: 1 (The N-H group in the indazole ring)
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Hydrogen Bond Acceptor Count: 3 (The two oxygen atoms in the ester and one nitrogen in the ring)
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Rotatable Bond Count: 2 (The bonds in the ester group)
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Topological Polar Surface Area (TPSA): 55 Ų
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Heavy Atom Count: 13
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Complexity: 208 (A relative measure of structural complexity)
Structural Depiction
The molecule consists of a planar indazole heterocyclic system (a benzene ring fused with a pyrazole ring) with a methyl ester group (-COOCH₃) attached at the 3-position.
Safety and Handling
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GHS Classification:
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Hazard Statement: H302 - Harmful if swallowed.
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Precautionary Statements: P264, P270, P301+P317, P330, P501.
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These advise measures such as washing hands thoroughly after handling, not eating or drinking while handling, and seeking medical advice if swallowed.
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Hazard Pictogram: GHS07 (Exclamation mark), indicating it is an irritant and/or has specific target organ toxicity after single exposure (in this case, harmful if swallowed).
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Signal Word: Warning