15802-75-2

Basic information

• Product Name: 3-Methyl-4-iodopyrazole
• Synonyms: 3-Methyl-4-iodopyrazole;4-Iodo-3-methyl-1H-pyrazole;4-LODO-3-METHYL PYRAZOLE;4-Iodo-3-methylpyrazole AldrichCPR;4-iodo-3-methyl-2H-pyrazole
• CAS NO: 15802-75-2
• Molecular Formula: C₄H₅IN₂
• Molecular Weight: 208
• Mol File: 15802-75-2.mol
• Article Data: 7

Chemical Properties

• Melting Point: 185-187 °C
• Boiling Point: 292.112 °C at 760 mmHg
• Flash Point: 130.465 °C
• Appearance: /
• Density: 2.094 g/cm³
• Vapor Pressure: 0.003mmHg at 25°C
• Refractive Index: 1.656
• Storage Temp.: 2-8°C(protect from light)
• PKA: 13.55±0.50(Predicted)
• CAS DataBase Reference: 3-Methyl-4-iodopyrazole(CAS DataBase Reference)
• NIST Chemistry Reference: 3-Methyl-4-iodopyrazole(15802-75-2)
• EPA Substance Registry System: 3-Methyl-4-iodopyrazole(15802-75-2)

Safety Data

• Hazard Codes: Xi,Xn
• Statements: 22
• HazardClass: IRRITANT
• Hazardous Substances Data: 15802-75-2(Hazardous Substances Data)

Usage

Uses

4-Iodo-3-methyl-1H-pyrazole is an analog of 4-Bromo-3-methylpyrazole (B688090) which is an intermdiate used to prepare substituted piperidines as potent, selective, CNS-penetrant α4β2 nicotinic acetylcholine receptor potentiators. 4-Bromo-3-methylpyrazole is also used to prepare small molecular B2 receptor antagonists.

InChI:InChI=1/C4H5IN2/c1-3-4(5)2-6-7-3/h2H,1H3,(H,6,7)

Synthetic route

3-Methylpyrazole (1453-58-3) → 4-iodo-3-methyl-1H-pyrazole (15802-75-2)

Conditions	Yield
With sodium hydroxide; Rodapon N 50; iodine In water at 20℃; for 0.25h;	90%
With ammonium cerium(IV) nitrate; iodine In acetonitrile at 20℃; for 3h;	90%
With dihydrogen peroxide; iodine In water	85.6%
With sodium nitrate; sodium hydrogencarbonate; potassium iodide In chloroform; water at 30℃; Electrolysis;	71%
With water; iodine; sodium acetate; potassium iodide

4-iodo-3,5-dimethyl-1H-pyrazole (2033-45-6) → 4-iodo-3-methyl-1H-pyrazole (15802-75-2) + 4-iodo-pyrazole-carboxylic acid-(3)

Conditions	Yield
With sodium hydroxide; potassium permanganate

4-iodo-3,5-dimethyl-1H-pyrazole (2033-45-6) + potassium permanganate + alkali → 4-iodo-3-methyl-1H-pyrazole (15802-75-2) + 4-iodo-pyrazole-carboxylic acid-(3)

3-Methylpyrazole (1453-58-3) → 4-iodo-3-methyl-1H-pyrazole (15802-75-2) + 3-iodo-2-methyl-1H-pyrazole (15802-75-2)

Conditions	Yield
With iodine; iodic acid In tetrachloromethane; water; acetic acid at 50℃; for 1.5h; Title compound not separated from byproducts.;

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione (58-08-2) + 4-iodo-3-methyl-1H-pyrazole (15802-75-2) → 4,5,8-tris(4-iodo-3-methyl-1H-pyrazol-1-yl)-1,3,7-trimethyl-3,4,5,7-tetrahydro-1H-purine-2,6-dione

Conditions	Yield
With tetrabutylammonium tetrafluoroborate In acetonitrile at 45℃; for 10h; Inert atmosphere; Electrochemical reaction; Green chemistry; diastereoselective reaction;	97%

4-iodo-3-methyl-1H-pyrazole (15802-75-2) → 3-methyl-4-nitro-1H-pyrazole (5334-39-4)

Conditions	Yield
With nitric acid In tetrahydrofuran at 20℃; for 2h;	92%
With nitric acid In tetrahydrofuran; water at 20℃; for 3h;	73%

4-iodo-3-methyl-1H-pyrazole (15802-75-2) + 4-carboxyphenylboronic acid (14047-29-1) + 2-bromo-5-[4-(6-bromopyridin-3-yl)phenyl]pyridine (207726-97-4) → C38H28N6O4

Conditions

Yield

Stage #1: 4-iodo-3-methyl-1H-pyrazole; 2-bromo-5-[4-(6-bromopyridin-3-yl)phenyl]pyridine With t-BuBrettPhos; palladium diacetate; sodium t-butanolate In toluene at 110℃; for 24h; Inert atmosphere; Schlenk technique; Stage #2: 4-carboxyphenylboronic acid With sodium 2'‐(dicyclohexylphosphaneyl)‐2,6‐diisopropyl‐[1,1'‐biphenyl]‐4‐sulfonate; palladium diacetate; potassium carbonate In water; toluene at 100℃; for 24h; Inert atmosphere; Schlenk technique;

77%

4-iodo-3-methyl-1H-pyrazole (15802-75-2) + acrylic acid methyl ester (292638-85-8) → methyl 3-(4-iodo-1H-pyrazol-1-yl)propanoate (1175275-82-7)

Conditions	Yield
With 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 0 - 20℃; for 2h;	77%

benzene-1,3-dicarboxylic-5-boronic triacid + 4-iodo-3-methyl-1H-pyrazole (15802-75-2) + 3,6-diiodo-1,2,4,5-tetrazine → C26H18N8O8

Conditions

Yield

Stage #1: 4-iodo-3-methyl-1H-pyrazole; 3,6-diiodo-1,2,4,5-tetrazine With t-BuBrettPhos; palladium diacetate; sodium t-butanolate In toluene at 110℃; for 18h; Inert atmosphere; Schlenk technique; Stage #2: benzene-1,3-dicarboxylic-5-boronic triacid With sodium 2'‐(dicyclohexylphosphaneyl)‐2,6‐diisopropyl‐[1,1'‐biphenyl]‐4‐sulfonate; palladium diacetate; caesium carbonate In water; toluene at 100℃; for 48h; Inert atmosphere; Schlenk technique;

76%

4-iodo-3-methyl-1H-pyrazole (15802-75-2) + 4-carboxyphenylboronic acid (14047-29-1) + 4,4'-bis[5-(2-bromopyridyl)]1,1'-biphenyl (263012-59-5) → C44H32N6O4

Conditions

Yield

Stage #1: 4-iodo-3-methyl-1H-pyrazole; 4,4'-bis[5-(2-bromopyridyl)]1,1'-biphenyl With t-BuBrettPhos; palladium diacetate; sodium t-butanolate In toluene at 110℃; for 18h; Inert atmosphere; Schlenk technique; Stage #2: 4-carboxyphenylboronic acid With sodium 2'‐(dicyclohexylphosphaneyl)‐2,6‐diisopropyl‐[1,1'‐biphenyl]‐4‐sulfonate; palladium diacetate; sodium carbonate In water; toluene at 100℃; for 36h; Inert atmosphere; Schlenk technique;

73%

4-iodo-3-methyl-1H-pyrazole (15802-75-2) + 4-carboxyphenylboronic acid (14047-29-1) + C8H4I2N4 → C30H22N8O4

Conditions

Yield

Stage #1: 4-iodo-3-methyl-1H-pyrazole; C8H4I2N4 With t-BuBrettPhos; palladium diacetate; sodium t-butanolate In toluene at 110℃; for 24h; Inert atmosphere; Schlenk technique; Stage #2: 4-carboxyphenylboronic acid With sodium 2'‐(dicyclohexylphosphaneyl)‐2,6‐diisopropyl‐[1,1'‐biphenyl]‐4‐sulfonate; palladium diacetate; sodium carbonate In toluene at 100℃; for 24h; Inert atmosphere; Schlenk technique;

72%

benzene-1,3-dicarboxylic-5-boronic triacid + 4-iodo-3-methyl-1H-pyrazole (15802-75-2) + 2-bromo-5-[4-(6-bromopyridin-3-yl)phenyl]pyridine (207726-97-4) → C40H28N6O8

Conditions

Yield

Stage #1: 4-iodo-3-methyl-1H-pyrazole; 2-bromo-5-[4-(6-bromopyridin-3-yl)phenyl]pyridine With t-BuBrettPhos; potassium tert-butylate; palladium diacetate In 1,4-dioxane at 110℃; for 24h; Inert atmosphere; Schlenk technique; Stage #2: benzene-1,3-dicarboxylic-5-boronic triacid With sodium 2'‐(dicyclohexylphosphaneyl)‐2,6‐diisopropyl‐[1,1'‐biphenyl]‐4‐sulfonate; palladium diacetate; potassium carbonate In 1,4-dioxane at 100℃; for 40h; Inert atmosphere; Schlenk technique;

68%

4-iodo-3-methyl-1H-pyrazole (15802-75-2) + 2-carboxyphenylboronic acid (149105-19-1) + 6,6’-dibromo-3,3’-bipyridine (147496-14-8) → C32H24N6O4

Conditions

Yield

Stage #1: 4-iodo-3-methyl-1H-pyrazole; 6,6’-dibromo-3,3’-bipyridine With t-BuBrettPhos; palladium diacetate; sodium t-butanolate In toluene at 110℃; for 24h; Inert atmosphere; Schlenk technique; Stage #2: 2-carboxyphenylboronic acid With sodium 2'‐(dicyclohexylphosphaneyl)‐2,6‐diisopropyl‐[1,1'‐biphenyl]‐4‐sulfonate; palladium diacetate; potassium carbonate In water; toluene at 100℃; for 48h; Inert atmosphere; Schlenk technique;

67%

4-iodo-3-methyl-1H-pyrazole (15802-75-2) + 4-methoxy-phenol (150-76-5) → 2-(4-iodo-3-methyl-1H-pyrazol-1-yl)-4-methoxyphenol

Conditions	Yield
With dipotassium peroxodisulfate In acetonitrile at 80℃; for 5h; Inert atmosphere; Schlenk technique;	67%

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione (58-08-2) + 4-iodo-3-methyl-1H-pyrazole (15802-75-2) → 8-(4-iodo-3-methyl-1H-pyrazol-1-yl)-1,3,7-trimethyl-3,7-dihydro-1H-purine-2,6-dione

Conditions	Yield
With tetrabutylammonium tetrafluoroborate In dimethyl sulfoxide; acetonitrile at 45℃; for 3h; Inert atmosphere; Electrochemical reaction; Green chemistry;	50%

4-iodo-3-methyl-1H-pyrazole (15802-75-2) + 2,5-difluoropyridine (84476-99-3) → C9H7FIN3

Conditions	Yield
With caesium carbonate In N,N-dimethyl-formamide at 25 - 90℃; for 6h;	42.89%

3,4-dihydro-2H-pyran (110-87-2) + 4-iodo-3-methyl-1H-pyrazole (15802-75-2) → 4-iodo-5-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazole (1072709-33-1) + C9H13IN2O

Conditions	Yield
Stage #1: 3,4-dihydro-2H-pyran; 4-iodo-3-methyl-1H-pyrazole With trifluoroacetic acid In tetrahydrofuran at 60℃; for 4h; Stage #2: With water; sodium carbonate In tetrahydrofuran; tert-butyl methyl ether

4-iodo-3-methyl-1H-pyrazole (15802-75-2) + methanesulfonic acid cyclopent-3-enyl ester (253680-54-5) → 1-(Cyclopent-3-en-1-yl)-4-iodo-5-methyl-1H-pyrazole (1350323-30-6) + 1-(Cyclopent-3-en-1-yl)-4-iodo-3-methyl-1H-pyrazole (1350323-31-7)

Conditions	Yield
Stage #1: 4-iodo-3-methyl-1H-pyrazole With sodium hydride In N,N-dimethyl-formamide at 20℃; for 1h; Stage #2: methanesulfonic acid cyclopent-3-enyl ester In N,N-dimethyl-formamide at 60℃;

4-iodo-3-methyl-1H-pyrazole (15802-75-2) + ethyl (1s,4s)-4-(p-tolylsulfonyloxy)cyclohexanecarboxylate (93164-43-3) → ethyl trans-4-(4-iodo-3-methyl-1H-pyrazol-1-yl)cyclohexanecarboxylate (1350322-91-6) + ethyl trans-4-(4-iodo-5-methyl-1H-pyrazol-1-yl)cyclohexanecarboxylate (1350322-93-8)

Conditions	Yield
With 18-crown-6 ether; potassium carbonate In N,N-dimethyl-formamide at 80℃; Product distribution / selectivity;

4-iodo-3-methyl-1H-pyrazole (15802-75-2) + 1-[(3-bromopropoxy)methyl]-benzene (54314-84-0) → 1-[3-(benzyloxy)propyl]-4-iodo-3-methyl-1H-pyrazole (1380306-11-5) + 1-[3-(benzyloxy)propyl]-4-iodo-5-methyl-1H-pyrazole (1380306-13-7)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 16h;

2-ethylthiophene (872-55-9) + 4-iodo-3-methyl-1H-pyrazole (15802-75-2) → C10H11IN2S + C10H11IN2S

Conditions	Yield
With tert.-butylnitrite; oxygen; 2,3-dicyano-5,6-dichloro-p-benzoquinone In 1,2-dichloro-ethane at 20℃; for 12h; Overall yield = 62 %;

4-iodo-3-methyl-1H-pyrazole (15802-75-2) + 2-amino-4-chloropyrimidine (3993-78-0) → 4-(4-iodo-3-methyl-1H-pyrazol-1-yl)pyrimidin-2-amine

Conditions	Yield
Stage #1: 4-iodo-3-methyl-1H-pyrazole With sodium hydride In N,N-dimethyl-formamide at 0 - 20℃; for 0.25h; Inert atmosphere; Stage #2: 2-amino-4-chloropyrimidine In N,N-dimethyl-formamide at 20℃; for 1h; Inert atmosphere;

4-iodo-3-methyl-1H-pyrazole (15802-75-2) + (rac)-1-(2,4-bis(trifluoromethyl)phenyl)ethanol → 1-(1-(2,4-bis(trifluoromethyl)phenyl)ethyl)-4-iodo-3-methyl-1H-pyrazole

Conditions	Yield
With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 20℃; for 16h;	50 mg

Upstream product

• 88054-14-2 3⁽⁵⁾-methylpyrazole 
• 2033-45-6 4-iodo-3,5-dimethyl-1H-pyrazole 
• 1453-58-3 3-Methylpyrazole 

Downstream Products

• 1175275-82-7 methyl 3-(4-iodo-1H-pyrazol-1-yl)propanoate 
• 1430752-41-2 1((4-iodo-5-methyl-1H-pyrazol-1-yl)methyl)cyclohexanol 
• 5334-39-4 3-methyl-4-nitro-1H-pyrazole 
• 1380306-11-5 1-[3-(benzyloxy)propyl]-4-iodo-3-methyl-1H-pyrazole 
• 1380306-13-7 1-[3-(benzyloxy)propyl]-4-iodo-5-methyl-1H-pyrazole 
• 1350322-91-6 ethyl trans-4-(4-iodo-3-methyl-1H-pyrazol-1-yl)cyclohexanecarboxylate 
• 1350322-93-8 ethyl trans-4-(4-iodo-5-methyl-1H-pyrazol-1-yl)cyclohexanecarboxylate 
• 6647-93-4 4-iodopyrazole-3⁽⁵⁾-carboxylic acid 

Relevant articles and documents

A mild and efficient method for the regioselective iodination of pyrazoles

The iodination of N-H or N-benzylpyrazoles using elemental iodine in the presence of CAN as the in situ oxidant is a mild and efficient method to prepare 4-iodopyrazoles containing even electron-withdrawing substituents. The reaction is regioselective since the iodine atom preferred pyrazole instead of the benzyl group, and the 4-pyrazolic position instead of other possible positions in the heterocycle.

Method for synthesizing 1 - methyl -4 -iodo pyrazole (by machine translation)

The invention relates to the technical field 1 - methyl -4 - iodinol synthesis, in particular to a synthesis method of 1 - methyl -4 - iodo pyrazole. The synthesis method of 1 - methyl -4 - iodinol comprises the following steps: (1) mixing 1 - methylpyrazole with iodine, heating to 40 - 80 °C, dropwise adding an oxidizing agent aqueous solution to carry out iodination reaction, and (2) adding alkali liquor to 5 - 9 DEG C to obtain a light yellow crystal, namely 1 - methyl -4 - iodo pyrazole. To 1 - methyl -4 - iodinol synthesis method, 1 - methylpyrazole raw materials are used as the iodinating agent, and an oxidizing agent, an oxidizing agent and hydrogen iodide are added to generate iodine, so that iodine is fully utilized, the reaction rate and product yield are improved, and the synthesis cost 1 - methyl -4 -iodo pyrazole is greatly reduced. (by machine translation)

Electrosynthesis of 4-iodopyrazole and its derivatives

Electrosynthesis of 4-iodo-substituted pyrazoles has been accomplished by iodination of the corresponding precursors on a Pt-anode in aqueous solutions of KI under conditions of the diaphragm galvanostatic electrolysis. Efficiency of the process depends on the donor-acceptor properties of substituents and their positions in the pyrazole ring. Thus, iodination of pyrazole, 3,5-dimethylpyrazole, 3-nitropyrazole, 1-methylpyrazole, 1,3-dimethylpyrazole, pyrazole-3(5)-carboxylic acid or methyl esters furnished 4-iodo derivatives in 57, 86, 2, 5, 35, 30, and 40% yields, respectively.