768398-03-4

Basic information

• Product Name: (6-METHYL-2-P-TOLYL-IMIDAZO[1,2-A]PYRIDIN-3-YL)-ACETONITRILE
• Synonyms: (6-METHYL-2-P-TOLYL-IMIDAZO[1,2-A]PYRIDIN-3-YL)-ACETONITRILE;IMidazo[1,2-a]pyridine-3-acetonitrile, 6-Methyl-2-(4-Methylphenyl)-;Zolpidem IV;2-(6-Methyl-2-(p-tolyl)imidazo[1,2-a]pyridin-3-yl)acetonitrile
• CAS NO: 768398-03-4
• Molecular Formula: C₁₇H₁₅N₃
• Molecular Weight: 261.32
• Mol File: 768398-03-4.mol
• Article Data: 10

Chemical Properties

• Appearance: /
• Density: 1.12g/cm³
• Refractive Index: 1.625
• Storage Temp.: -20°C Freezer, Under inert atmosphere
• Solubility: Chloroform (Slightly), Ethyl Acetate (Slightly)
• PKA: 5.86±0.50(Predicted)
• CAS DataBase Reference: (6-METHYL-2-P-TOLYL-IMIDAZO[1,2-A]PYRIDIN-3-YL)-ACETONITRILE(CAS DataBase Reference)
• NIST Chemistry Reference: (6-METHYL-2-P-TOLYL-IMIDAZO[1,2-A]PYRIDIN-3-YL)-ACETONITRILE(768398-03-4)
• EPA Substance Registry System: (6-METHYL-2-P-TOLYL-IMIDAZO[1,2-A]PYRIDIN-3-YL)-ACETONITRILE(768398-03-4)

Safety Data

• Hazardous Substances Data: 768398-03-4(Hazardous Substances Data)

Usage

Uses

Impurity of Zolpidem (Z650000), a selective non-benzodiazepine GABAA receptor agonist.

InChI:InChI=1/C17H15N3/c1-12-3-6-14(7-4-12)17-15(9-10-18)20-11-13(2)5-8-16(20)19-17/h3-8,11H,9H2,1-2H3

Synthetic route

6-methyl-2-(4-methyl-phenyl)-imidazo[1,2-a]pyridine (88965-00-8) + cyanomethyl bromide (590-17-0) → 6-methyl-3-cyanomethyl-2-(4-methylphenyl)imidazo[1,2-a]pyridine (768398-03-4)

Conditions	Yield
With fac-tris(2-phenylpyridinato-N,C2')iridium(III); sodium hydrogencarbonate In dimethyl sulfoxide at 20℃; for 12h; Schlenk technique; Inert atmosphere; Irradiation; regioselective reaction;	85%

S-cyanomethyl O-ethyl carbonodithioate (59463-54-6) + 6-methyl-2-(4-methyl-phenyl)-imidazo[1,2-a]pyridine (88965-00-8) → 6-methyl-3-cyanomethyl-2-(4-methylphenyl)imidazo[1,2-a]pyridine (768398-03-4)

Conditions	Yield
With tris[2-phenylpyridinato-C2,N]iridium(III); N,N-dimethyl-formamide at 24℃; Minisci Aromatic Substitution; Inert atmosphere; UV-irradiation; regioselective reaction;	61%
With dilauryl peroxide In 1,2-dichloro-ethane at 85℃; Microwave irradiation; regioselective reaction;	51%

diazoacetonitrile (13138-21-1) + 6-methyl-2-(4-methyl-phenyl)-imidazo[1,2-a]pyridine (88965-00-8) → 6-methyl-3-cyanomethyl-2-(4-methylphenyl)imidazo[1,2-a]pyridine (768398-03-4)

Conditions	Yield
With iron(III) chloride In acetonitrile at 60℃; for 6h; Sealed tube; Green chemistry;	50%

6-methyl-2-(4-methyl-phenyl)-imidazo[1,2-a]pyridine (88965-00-8) + acetonitrile (75-05-8) → 6-methyl-3-cyanomethyl-2-(4-methylphenyl)imidazo[1,2-a]pyridine (768398-03-4)

Conditions	Yield
With ferrocene; bis(1-methyl-1-phenylethyl)peroxide at 20 - 100℃; for 20h; Inert atmosphere; Sealed tube;	48%

sodium cyanide (143-33-9) + Trimethyl-(6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-ammonium; iodide (106961-34-6) → 6-methyl-3-cyanomethyl-2-(4-methylphenyl)imidazo[1,2-a]pyridine (768398-03-4)

Conditions	Yield
Yield given;
In water at 82 - 84℃; for 12h;

potassium cyanide (151-50-8) + dimethyl-(6-methyl-2-p-tolylimidazo[1,2-a]pyridin-3-ylmethyl)-amine (106961-33-5) → 6-methyl-3-cyanomethyl-2-(4-methylphenyl)imidazo[1,2-a]pyridine (768398-03-4) + 2-(4-methylphenyl)-6-methylimidazo[1,2-α]pyridine-3-acetamide (365213-58-7)

Conditions	Yield
Stage #1: dimethyl-(6-methyl-2-p-tolylimidazo[1,2-a]pyridin-3-ylmethyl)-amine With methyl iodide In ethanol at 20℃; for 24h; Stage #2: potassium cyanide In ethanol; water for 4h; Heating;

6-methyl-2-(4-methyl-phenyl)-imidazo[1,2-a]pyridine (88965-00-8) → 6-methyl-3-cyanomethyl-2-(4-methylphenyl)imidazo[1,2-a]pyridine (768398-03-4)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: 78 percent / acetic acid / H2O / 4 h / 50 - 55 °C 2.1: MeI / ethanol / 24 h / 20 °C 2.2: H2O; ethanol / 4 h / Heating View Scheme
Multi-step reaction with 3 steps 1: 79 percent / AcOH View Scheme

dimethyl-(6-methyl-2-p-tolylimidazo[1,2-a]pyridin-3-ylmethyl)-amine (106961-33-5) → 6-methyl-3-cyanomethyl-2-(4-methylphenyl)imidazo[1,2-a]pyridine (768398-03-4)

C20H24N3O2(1+)*Cl(1-) (1101863-48-2) + sodium cyanide (143-33-9) → 6-methyl-3-cyanomethyl-2-(4-methylphenyl)imidazo[1,2-a]pyridine (768398-03-4)

Conditions	Yield
Stage #1: C20H24N3O2(1+)*Cl(1-) With sodium hydroxide; water pH=7.5 - 8; Stage #2: sodium cyanide In water at 50 - 55℃; for 3h; Product distribution / selectivity;

(5-methyl-pyridin-2-yl)amine (1603-41-4) → 6-methyl-3-cyanomethyl-2-(4-methylphenyl)imidazo[1,2-a]pyridine (768398-03-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium hydrogencarbonate / ethanol / 6 h / 20 °C / Inert atmosphere 2: ferrocene; bis(1-methyl-1-phenylethyl)peroxide / 20 h / 20 - 100 °C / Inert atmosphere; Sealed tube View Scheme

4-(bromoacetyl)toluene (619-41-0) → 6-methyl-3-cyanomethyl-2-(4-methylphenyl)imidazo[1,2-a]pyridine (768398-03-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium hydrogencarbonate / ethanol / 6 h / 20 °C / Inert atmosphere 2: ferrocene; bis(1-methyl-1-phenylethyl)peroxide / 20 h / 20 - 100 °C / Inert atmosphere; Sealed tube View Scheme

ethanol (64-17-5) + 6-methyl-3-cyanomethyl-2-(4-methylphenyl)imidazo[1,2-a]pyridine (768398-03-4) → ethyl 6-methyl-2-(4-methylphenyl)imidazo[1,2-a]pyridine-3-acetate (193979-47-4)

Conditions	Yield
With sulfuric acid; water at 90℃; for 12h;	95%
With sulfuric acid at 90℃; for 12h;	95%

6-methyl-3-cyanomethyl-2-(4-methylphenyl)imidazo[1,2-a]pyridine (768398-03-4) → 6-methyl-2-(4-methylphenyl)-imidazo<1,2-a>pyridine-3-acetic acid (189005-44-5)

Conditions	Yield
With hydrogenchloride; water	91%
Stage #1: 6-methyl-3-cyanomethyl-2-(4-methylphenyl)imidazo[1,2-a]pyridine With sulfuric acid; water at 110℃; for 4 - 5h; Stage #2: With sodium hydroxide; water at 0℃; pH=9; Stage #3: With water; acetic acid pH=5.5; Product distribution / selectivity;	72%
Stage #1: 6-methyl-3-cyanomethyl-2-(4-methylphenyl)imidazo[1,2-a]pyridine With hydrogenchloride In water at 25 - 100℃; for 12h; Heating / reflux; Stage #2: With potassium hydroxide In water at 25 - 105℃; for 2 - 3h; Stage #3: With acetic acid In water at 30 - 40℃;
Stage #1: 6-methyl-3-cyanomethyl-2-(4-methylphenyl)imidazo[1,2-a]pyridine With sodium hydroxide; water at 55 - 98℃; for 16.5h; Heating / reflux; Stage #2: With acetic acid In water at 25℃; for 4h; pH=5.3;
With sulfuric acid at 110℃; Inert atmosphere;

6-methyl-3-cyanomethyl-2-(4-methylphenyl)imidazo[1,2-a]pyridine (768398-03-4) → 3-((2H-tetrazol-5-yl)methyl)-6-methyl-2-p-tolylimidazo[1,2-a]pyridine (1387635-23-5)

Conditions	Yield
With indium(III) chloride; sodium azide In N,N-dimethyl-formamide for 0.166667h; Microwave irradiation;	76%

6-methyl-3-cyanomethyl-2-(4-methylphenyl)imidazo[1,2-a]pyridine (768398-03-4) → 1-Imidazol-1-yl-2-(6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-yl)-ethanone

Conditions	Yield
Multi-step reaction with 2 steps 1: 91 percent / H2O, HCl View Scheme

6-methyl-3-cyanomethyl-2-(4-methylphenyl)imidazo[1,2-a]pyridine (768398-03-4) → N,N,6-trimethyl-2-(4-methylphenyl)imidazo[1,2-a]pyridine-3-acetamide (82626-48-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: 91 percent / H2O, HCl View Scheme
Multi-step reaction with 2 steps 1.1: sulfuric acid / 110 °C / Inert atmosphere 2.1: phosphorus pentachloride / dichloromethane / Reflux; Inert atmosphere 2.2: 0 °C / Inert atmosphere View Scheme

Upstream product

• 13138-21-1 diazoacetonitrile 
• 88965-00-8 6-methyl-2-(4-methyl-phenyl)-imidazo[1,2-a]pyridine 
• 590-17-0 cyanomethyl bromide 
• 619-41-0 4-(bromoacetyl)toluene 
• 1603-41-4 (5-methyl-pyridin-2-yl)amine 
• 75-05-8 acetonitrile 
• 59463-54-6 S-cyanomethyl O-ethyl carbonodithioate 
• 1101863-48-2 C₂₀H₂₄N₃O₂⁽¹⁺⁾*Cl^(1-) 
• 143-33-9 sodium cyanide 
• 106961-33-5 dimethyl-(6-methyl-2-p-tolylimidazo[1,2-a]pyridin-3-ylmethyl)-amine 
• 151-50-8 potassium cyanide 
• 106961-34-6 Trimethyl-(6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-ammonium; iodide 

Downstream Products

• 193979-47-4 ethyl 6-methyl-2-(4-methylphenyl)imidazo[1,2-a]pyridine-3-acetate 
• 82626-48-0 N,N,6-trimethyl-2-(4-methylphenyl)imidazo[1,2-a]pyridine-3-acetamide 
• 1387635-23-5 3-((2H-tetrazol-5-yl)methyl)-6-methyl-2-p-tolylimidazo[1,2-a]pyridine 
• 189005-44-5 6-methyl-2-(4-methylphenyl)-imidazo<1,2-a>pyridine-3-acetic acid 

Relevant articles and documents

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