3758-59-6

Basic information

• Product Name: 4-Pyridinecarboxylic acid, 2-methyl-, hydrazide
• Synonyms: 4-Pyridinecarboxylic acid, 2-methyl-, hydrazide;4-Pyridinecarboxylic Acid, 2-Methyl-, Hydrazide HCl;2-Methylisonicotinohydrazide hydrochloride
• CAS NO: 3758-59-6
• Molecular Formula: C₇H₉N₃O
• Molecular Weight: 151.1659
• Mol File: 3758-59-6.mol
• Article Data: 8

Chemical Properties

• Boiling Point: °Cat760mmHg
• Flash Point: °C
• Appearance: /
• Density: 1.195g/cm³
• Refractive Index: 1.573
• CAS DataBase Reference: 4-Pyridinecarboxylic acid, 2-methyl-, hydrazide(CAS DataBase Reference)
• NIST Chemistry Reference: 4-Pyridinecarboxylic acid, 2-methyl-, hydrazide(3758-59-6)
• EPA Substance Registry System: 4-Pyridinecarboxylic acid, 2-methyl-, hydrazide(3758-59-6)

Safety Data

• Hazardous Substances Data: 3758-59-6(Hazardous Substances Data)

Usage

General Description

The chemical 4-Pyridinecarboxylic acid, 2-methyl-, hydrazide is also known as isonicotinoyl hydrazide. It is a hydrazide derivative of isonicotinic acid, and is commonly used in the synthesis of pharmaceuticals and agrochemicals. It is known for its antibacterial and antitubercular properties, and is used as a building block in the production of various drugs. It functions as a prodrug when administered orally, and is metabolized in the body to release the active drug, isoniazid. This chemical has potential applications in the treatment of tuberculosis and other infectious diseases, and is an important component of several pharmaceutical formulations.

InChI:InChI=1/C7H9N3O/c1-5-4-6(2-3-9-5)7(11)10-8/h2-4H,8H2,1H3,(H,10,11)

Synthetic route

methyl 2-methylisonicotinate (16830-24-3) → 2-methylisonicotinohydrazide (3758-59-6)

Conditions	Yield
With hydrazine In methanol at 20℃; for 18h;	86%
With ethanol; hydrazine hydrate
With methanol; hydrazine hydrate

2-chloro-6-methylisonicotinohydrazide (19353-99-2) → 2-methylisonicotinohydrazide (3758-59-6)

Conditions	Yield
With sodium hydroxide; palladium Hydrogenation;
With hydrogen; triethylamine; palladium 10% on activated carbon In ethanol at 20℃;

2-hydroxy-6-methylpyridine-4-carboxylic acid (86454-13-9) → 2-methylisonicotinohydrazide (3758-59-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: POCl3; PCl5 / Behandeln des Reaktionsprodukts mit Methanol 2: palladium/charcoal; methanol; potassium acetate / Hydrogenation 3: methanol; N2H4+H2O View Scheme

2-chloro-6-methyl-isonicotinic acid methyl ester (3998-90-1) → 2-methylisonicotinohydrazide (3758-59-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: palladium/charcoal; methanol; potassium acetate / Hydrogenation 2: methanol; N2H4+H2O View Scheme

2-methylisonicotinic acid (4021-11-8) → 2-methylisonicotinohydrazide (3758-59-6)

Conditions	Yield
With 1,1'-carbonyldiimidazole; hydrazine In tetrahydrofuran at 20℃;
Stage #1: 2-methylisonicotinic acid With 1,1'-carbonyldiimidazole In tetrahydrofuran at 20℃; for 1h; Stage #2: With hydrazine In tetrahydrofuran at 20℃; for 6h;

ethyl 2-methylpyridine-4-carboxylate (25635-17-0) → 2-methylisonicotinohydrazide (3758-59-6)

Conditions	Yield
With hydrazine hydrate In ethanol for 12h; Reflux;

2-methylisonicotinohydrazide (3758-59-6) + (R)-2-[5-(3-Cyano-phenyl)-isoxazol-3-yl]-N-methyl-pyrrolidine-1-carboximidothioic acid methyl ester → 3-(3-{1-[4-Methyl-5-(2-methyl-pyridin-4-yl)-4H-[1,2,4]triazol-3-yl]-pyrrolidin-2-yl}-isoxazol-5-yl)-benzonitrile

Conditions	Yield
In isopropyl alcohol at 90℃; for 24h;	55%

2-methylisonicotinohydrazide (3758-59-6) + (R,Z)-2-[2-(3-chloro-phenyl)-2H-tetrazol-5-yl]-N-methyl-pyrrolidine-1-carboximidothioic acid methyl ester → 4-(5-{(R)-2-[2-(3-Chloro-phenyl)-2H-tetrazol-5-yl]-pyrrolidin-1-yl}-4-methyl-4H-[1,2,4]triazol-3-yl)-2-methyl-pyridine

Conditions	Yield
In isopropyl alcohol at 90℃; for 24h;	47%

2-methylisonicotinohydrazide (3758-59-6) + 2-formylbenzene boronic acid (40138-16-7) → (E)-(2-((2-(2-methylisonicotinoyl)hydrazineylidene)methyl)phenyl)boronic acid

Conditions	Yield
In isopropyl alcohol at 20℃;	22%

2-methylisonicotinohydrazide (3758-59-6) + 7-[1-(tert-butoxycarbonyl)piperidin-4-yl]-5-oxo-4,5-dihydropyrazolo[1,5-a]pyrimidine-3-carboxylic acid → tert-butyl 4-(3-{[2-(2-methylisonicotinoyl)hydrazino]carbonyl}-5-oxo-4,5-dihydropyrazolo[1,5-a]pyrimidin-7-yl)piperidine-1-carboxylate

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; HATU In N,N-dimethyl-formamide at 20℃; for 16h;	12%

pyridine (110-86-1) + 2-methoxy-isonicotinic acid (105596-63-2) + 2-methylisonicotinohydrazide (3758-59-6) → N-(2-methoxy-isonicotinoyl)-N'-(2-methyl-isonicotinoyl)-hydrazine

Conditions	Yield
With thionyl chloride; benzene

pyridine (110-86-1) + 2-ethoxynicotinic acid + 2-methylisonicotinohydrazide (3758-59-6) → N-(2-ethoxy-isonicotinoyl)-N'-(2-methyl-isonicotinoyl)-hydrazine

Conditions	Yield

3-pyridinecarboxaldehyde (500-22-1) + 2-methylisonicotinohydrazide (3758-59-6) → 2-methyl-isonicotinic acid-([3]pyridylmethylene-hydrazide) (108874-58-4)

Conditions	Yield
With water

furfural (98-01-1) + 2-methylisonicotinohydrazide (3758-59-6) → 2-methyl-isonicotinic acid furfurylidenehydrazide (99989-13-6)

Conditions	Yield
With methanol

1-(2-furyl)-1-ethanone (1192-62-7) + 2-methylisonicotinohydrazide (3758-59-6) → 2-methyl-isonicotinic acid-(1-[2]furyl-ethylLiDenehydrazide) (109017-29-0)

Conditions	Yield
With ethanol

2-Acetylthiophene (88-15-3) + 2-methylisonicotinohydrazide (3758-59-6) → 2-methyl-isonicotinic acid-(1-[2]thienyl-ethylLiDenehydrazide) (105402-12-8)

Conditions	Yield
With ethanol

2-furancarbonyl chloride (527-69-5) + 2-methylisonicotinohydrazide (3758-59-6) → N-(furan-2-carbonyl)-N'-(2-methyl-isonicotinoyl)-hydrazine

Conditions	Yield
With pyridine

5-nitrofurane-2-carboxaldehyde (698-63-5) + 2-methylisonicotinohydrazide (3758-59-6) → 2-methyl-isonicotinic acid-(5-nitro-furfurylidenehydrazide) (100137-21-1)

Conditions	Yield
With methanol

(E)-3-phenylpropenal (14371-10-9) + 2-methylisonicotinohydrazide (3758-59-6) → 2-methyl-isonicotinic acid trans-cinnamylidenehydrazide

Conditions	Yield
With methanol

phosgene (75-44-5) + 2-methylisonicotinohydrazide (3758-59-6) → 5-(2-methyl-[4]pyridyl)-3H-[1,3,4]oxadiazol-2-one

Conditions	Yield
With water

formaldehyd (50-00-0) + 2-methylisonicotinohydrazide (3758-59-6) → 2-methyl-isonicotinic acid methylenehydrazide

Conditions	Yield

trans-Crotonaldehyde (123-73-9) + 2-methylisonicotinohydrazide (3758-59-6) → 2-methyl-isonicotinic acid but-2t-enylidenehydrazide (99856-93-6)

Conditions	Yield
With methanol

2-methylisonicotinohydrazide (3758-59-6) + piperonal (120-57-0) → 2-methyl-isonicotinic acid piperonylidenehydrazide (101101-91-1)

Conditions	Yield
With ethanol

2-methylisonicotinohydrazide (3758-59-6) + 4-methyl-pent-3-en-2-one (141-79-7) → 4-methyl-4-[N'-(2-methyl-isonicotinoyl)-hydrazino]-pentan-2-one-(2-methyl-isonicotinoylhydrazone)

Conditions	Yield
With ethanol

2-methylisonicotinohydrazide (3758-59-6) + 2,2-dimethyl-3-hydroxypropionaldehyde (597-31-9) → 2-methyl-isonicotinic acid-(3-hydroxy-2,2-dimethyl-propylidenehydrazide) (100318-48-7)

Conditions	Yield
With ethanol

2-methylisonicotinohydrazide (3758-59-6) + 2,6-diethoxy-isonicotinoyl chloride (875249-18-6) → N-(2,6-diethoxy-isonicotinoyl)-N'-(2-methyl-isonicotinoyl)-hydrazine

Conditions	Yield
With pyridine

2-methylisonicotinohydrazide (3758-59-6) + undec-10-enoyl chloride (38460-95-6) → N-(2-methyl-isonicotinoyl)-N'-undec-10-enoyl-hydrazine

Conditions	Yield
With pyridine

2-methylisonicotinohydrazide (3758-59-6) + α-ketoglutaric acid (328-50-7) → 2-(2-methyl-isonicotinoylhydrazono)-glutaric acid

Conditions	Yield
With water

2-methylisonicotinohydrazide (3758-59-6) + Glyoxal (131543-46-9) → glyoxal-bis-(2-methyl-isonicotinoylhydrazone) (130936-01-5)

Conditions	Yield
With water

2-methylisonicotinohydrazide (3758-59-6) + butanedial (638-37-9) → succinaldehyde-bis-(2-methyl-isonicotinoylhydrazone) (110062-08-3)

Conditions	Yield
With water

2-methylisonicotinohydrazide (3758-59-6) + 5-formylvanillin (2931-90-0) → 4-hydroxy-5-methoxy-isophthalaldehyde-bis-(2-methyl-isonicotinoylhydrazone) (122472-76-8)

Conditions	Yield
With ethanol

2-methylisonicotinohydrazide (3758-59-6) + (E,E,E)-2,6-dimethyl-8-(2,6,6-trimethylcyclohex-1-enyl)octa-2,4,6-trienal (50876-26-1) → 2-methyl-isonicotinic acid-[2,6-dimethyl-8-(2,6,6-trimethyl-cyclohex-1-enyl)-octa-2t,4t,6t-trienylidenehydrazide]

Conditions	Yield
With ethanol

2-methylisonicotinohydrazide (3758-59-6) + isonicotinoyl chloride hydrochloride (39178-35-3) → N-isonicotinoyl-N'-(2-methyl-isonicotinoyl)-hydrazine

Conditions	Yield
With pyridine

2-methylisonicotinohydrazide (3758-59-6) + cyclohexanone (108-94-1) → 2-methyl-isonicotinic acid cyclohexyLiDenehydrazide

Conditions	Yield
With water

Upstream product

• 16830-24-3 methyl 2-methylisonicotinate 
• 19353-99-2 2-chloro-6-methylisonicotinohydrazide 
• 4021-11-8 2-methylisonicotinic acid 
• 25635-17-0 ethyl 2-methylpyridine-4-carboxylate 
• 3998-90-1 2-chloro-6-methyl-isonicotinic acid methyl ester 
• 86454-13-9 2-hydroxy-6-methylpyridine-4-carboxylic acid 

Downstream Products

• 122472-76-8 4-hydroxy-5-methoxy-isophthalaldehyde-bis-(2-methyl-isonicotinoylhydrazone) 
• 107455-74-3 2-methyl-isonicotinic acid-(4-nitro-benzylidenehydrazide) 
• 101281-47-4 2-methyl-isonicotinic acid-(4-acetylamino-benzylidenehydrazide) 
• 100867-61-6 2-methyl-isonicotinic acid benzylidenehydrazide 
• 107922-67-8 2-methyl-isonicotinic acid-(4-hydroxy-benzylidenehydrazide) 
• 101091-51-4 2-methyl-isonicotinic acid-(4-methoxy-benzylidenehydrazide) 
• 101091-68-3 2-methyl-isonicotinic acid vanillylidenehydrazide 
• 101091-22-9 2-methyl-isonicotinic acid-(1-phenyl-ethylLiDenehydrazide) 
• 103041-64-1 2-methyl-isonicotinic acid-(1-phenyl-propylidenehydrazide) 
• 101289-92-3 2-methyl-isonicotinic acid-(4-dimethylamino-benzylidenehydrazide) 
• 101091-50-3 2-methyl-isonicotinic acid-[1-(4-hydroxy-phenyl)-ethylLiDenehydrazide] 

Relevant articles and documents

Reinvestigation of the structure-activity relationships of isoniazid

Isoniazid (INH) remains a cornerstone for treatment of drug susceptible tuberculosis (TB), yet the quantitative structure-activity relationships for INH are not well documented in the literature. In this paper, we have evaluated a systematic series of INH analogs against contemporary Mycobacterium tuberculosis strains from different lineages and a few non-tuberculous mycobacteria (NTM). Deletion of the pyridyl nitrogen atom, isomerization of the pyridine nitrogen to other positions, replacement of the pyridine ring with isosteric heterocycles, and modification of the hydrazide moiety of INH abolishes antitubercular activity. Similarly, substitution of the pyridine ring at the 3-position is not tolerated while substitution at the 2-position is permitted with 2-methyl-INH 9 displaying antimycobacterial activity comparable to INH. To assess the specific activity of this series of INH analogs against mycobacteria, we assayed them against a panel of gram-positive and gram-negative bacteria, as well as a few fungi. As expected INH and its analogs display a narrow spectrum of activity and are inactive against all non-mycobacterial strains evaluated, except for 4, which has modest inhibitory activity against Cryptococcus neoformans. Our findings provide an updated analysis of the structure-activity relationship of INH that we hope will serve as useful resource for the community.

Design, synthesis, and pharmacological and pharmacokinetic evaluation of 3-phenyl-5-pyridyl-1,2,4-triazole derivatives as xanthine oxidoreductase inhibitors

In an effort to find a potent xanthine oxidoreductase (XO) inhibitor, we discovered the best compound 2-[2-(2-methoxy-ethoxy)-ethoxy]-5-[5-(2-methyl-pyridin-4-yl)-1H-[1,2,4]triazol-3-yl]-benzonitrile 28. Here, we describe the following: (1) the design, synthesis, and structure-activity relationship of a series of 3-phenyl-5-pyridyl-1,2,4-triazole derivatives by in vitro studies of XO inhibitory activity in bovine milk and in vivo studies of serum uric acid (UA) reductive activity in rats, (2) a drug interaction study by a cytochrome P450 3A4 (CYP3A4) assay, and (3) a pharmacokinetic (PK) study. Compound 28 exhibits potent XO inhibitory activity, serum UA-lowering activity in rats, weak CYP3A4 inhibitory activity, and moderate PK profile.

MGluR5 modulators IV

The present invention is directed to novel compounds, to a process for their preparation, their use in therapy and pharmaceutical compositions comprising the novel compounds.