114601-31-9

Basic information

• Product Name: Cyano temozolomide
• Synonyms: Temozolomide Cyano Impurity;8-Descarboxamido-8-cyano Temozolomide
• CAS NO: 114601-31-9
• Molecular Formula: C₆H₄N₆O
• Molecular Weight: 176.13556
• Mol File: 114601-31-9.mol
• Article Data: 3

Chemical Properties

• Boiling Point: 415.285 °C at 760 mmHg
• Flash Point: 204.958 °C
• Appearance: /
• Density: 1.743 g/cm³
• PKA: -1.85±0.20(Predicted)
• CAS DataBase Reference: Cyano temozolomide(CAS DataBase Reference)
• NIST Chemistry Reference: Cyano temozolomide(114601-31-9)
• EPA Substance Registry System: Cyano temozolomide(114601-31-9)

Safety Data

• Hazardous Substances Data: 114601-31-9(Hazardous Substances Data)

Usage

Uses

8-Descarboxamido-8-cyano Temozolomide is a useful synthetic intermediate in the synthesis of Temozolomide (T017775); an imidazotetrazine alkylating agent and antineoplastic.

Synthetic route

temozolomide (85622-93-1) → cyanotemozolomide (114601-31-9)

Conditions	Yield
With thionyl chloride In N,N-dimethyl-formamide at 60℃;	78%

4-diazo-4H-imidazole-5-carbonitrile (53000-41-2) + methyl isocyanate (624-83-9) → cyanotemozolomide (114601-31-9)

Conditions	Yield
In dimethyl sulfoxide at 25℃; for 24h;	52%

5-amino-1-(N-methylcarbamoyl)imidazole-4-carbonitrile (196806-16-3) → cyanotemozolomide (114601-31-9)

Conditions	Yield
With acetic acid; sodium nitrite In water at 0℃; for 1.5h;	23 % Chromat.

5-{3-methyl-3-[(phenyloxy)carbonyl]triazen-1-yl}imidazole-4-carbonitrile → cyanotemozolomide (114601-31-9)

Conditions	Yield
In dimethylsulfoxide-d6 for 0.5h; daylight;	46 % Spectr.

C17H18N6O3 (1025840-09-8) → cyanotemozolomide (114601-31-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: 2.05 g / TFA / acetic acid; methanol / 5 h / 20 °C 2: 46 percent Spectr. / dimethylsulfoxide-d6 / 0.5 h / daylight View Scheme

cyanotemozolomide (114601-31-9) → 8-carbamoyl-3-methyl-imidazo[5,1-d]-1,2,3,5-tetrazin-4(3H)-one hydrochloride

Conditions	Yield
With hydrogenchloride at 32 - 35℃; for 3h;	89.3%
With hydrogenchloride at 60℃; for 2h;	65%

Upstream product

• 196806-16-3 5-amino-1-(N-methylcarbamoyl)imidazole-4-carbonitrile 
• 85622-93-1 temozolomide 
• 1025840-09-8 C₁₇H₁₈N₆O₃ 
• 53000-41-2 4-diazo-4H-imidazole-5-carbonitrile 
• 624-83-9 methyl isocyanate 

Relevant articles and documents

Antitumor Imidazotetrazines. 35. New Synthetic Routes to the Antitumor Drug Temozolomide

Three new pathways to the antitumor drug temozolomide (4) have been explored via intermediates 3, 6, and 7. The key intermediate 5-amino-1-(N-methylcarbamoyl)imidazole-4-carboxamide (6) has been successfully converted to 4 in 45% yield by employing sodium nitrite in aqueous tartaric acid at 0-5°C. Compound 6 is prepared from nitrophenyl carbamate 14a and methylamine or directly from 5-aminoimidazole-4-carboxamide (13) and either methyl isocyanate or N-methylcarbamoyl chloride. Temozolomide (4) is also prepared from 8-cyano-3-methylimidazo[5,1-d]-l,2,3,5-tetrazin4(3H)-One (7) by hydrolysis to the hydrochloride salt of 4 in 10 M hydrochloric acid. Compound 7 is prepared from either 5-diazoimidazole-4-carbonitrile (28) and methyl isocyanate or by diazotization of 5-amino-1-(N-methylcarbamoyl)imidazole-4-carbonitrile (25). Attempts to cyclize 5-(3-methyltriazen-1-yl)imidazole-4-carboxamide (3) with phosgene or phosgene equivalents were unsuccessful: only 2-azahypoxanthine (11) was isolated.

A new synthesis of temozolomide

An efficient condensation reaction for the synthesis of phenyloxycarbonyl substituted triazenylimidazoles was described. The condensation reaction made use of nitrosoimidazoles and phenyl methylcarbazate as the reacting products. The exposure of the triazenes to diffuse daylight induced the isomerization of the triazene-nitrogen bonds, resulting in a high yield of temozolomide.