91702-61-3

Basic information

• Product Name: Acyclovir IMpurity C
• Synonyms: Acyclovir IMpurity C;2-AMino-1,7-dihydro-7-[(2-hydroxyethoxy)Methyl]-6H-purin-6-one;N7-[(2-Hydroxyethoxy)Methyl)guanine;Acyclovir Impurity C: 2-Amino-7-[(2-hydroxyethoxy)- methyl]-1,7-dihydro-6H-purin-6-one;Acyclovir Impurity 19;2-amino-7-[(2-hydroxyethoxy)methyl]-7H-purin-6-ol;7-(2-Hydroxyethoxymethyl)guanine
• CAS NO: 91702-61-3
• Molecular Formula: C₈H₁₁N₅O₃
• Molecular Weight: 225.20464
• Product Categories: Bases & Related Reagents;Intermediates & Fine Chemicals;Nucleotides;Pharmaceuticals
• Mol File: 91702-61-3.mol
• Article Data: 4

Chemical Properties

• Melting Point: >280 °C (decomp)
• Appearance: /
• Density: 1.77±0.1 g/cm3(Predicted)
• PKA: 9.46±0.20(Predicted)
• CAS DataBase Reference: Acyclovir IMpurity C(CAS DataBase Reference)
• NIST Chemistry Reference: Acyclovir IMpurity C(91702-61-3)
• EPA Substance Registry System: Acyclovir IMpurity C(91702-61-3)

Safety Data

• Hazardous Substances Data: 91702-61-3(Hazardous Substances Data)

Usage

Uses

N7-[(2-Hydroxyethoxy)methyl)guanine is the 7-isomeric impurity of the antiviral drug Acyclovir (A192400).

Synthetic route

7-<(2-acetoxyethoxy)methyl>-N2-acetylguanine (91702-60-2) → 7-(2-Hydroxyethoxymethyl)guanine (91702-61-3)

Conditions	Yield
With methylamine at 80℃; for 0.5h;	82%

7-[[2-(p-methoxyphenyloxy)ethoxy]methyl]guanine (374678-34-9) → 7-(2-Hydroxyethoxymethyl)guanine (91702-61-3)

Conditions	Yield
With ammonium cerium(IV) nitrate In water; acetonitrile at 0 - 25℃; for 1h;	70%
With NH4Ca(NO3)3 In water; acetonitrile	70%

2-acetoxyethyl acetoxymethyl ether (59278-00-1) + acetic anhydride (108-24-7) + G (118-00-3) → acycloguanosine (59277-89-3) + 7-(2-Hydroxyethoxymethyl)guanine (91702-61-3)

Conditions	Yield
With sodium hydroxide; toluene-4-sulfonic acid 1.) 100 deg C, 20 h, 2.) room temperature, overnight; Yield given. Multistep reaction;	A n/a B 0.5%

2-amino-1,9-dihydro-6H-purin-6-one (73-40-5) → 7-(2-Hydroxyethoxymethyl)guanine (91702-61-3)

Conditions	Yield
Multi-step reaction with 5 steps 1: (NH4)2SO4 / 24 h / Heating 2: 3.54 g / acetonitrile / 7 h / 25 °C 3: 88 percent / dimethylformamide / 8 h / 25 °C 4: 82 percent / dimethylformamide / 25 °C 5: 70 percent / ceric ammonium nitrate / acetonitrile; H2O / 1 h / 0 - 25 °C View Scheme

6-Trimethylsilanyloxy-9H-purin-2-ylamine (890044-83-4) → 7-(2-Hydroxyethoxymethyl)guanine (91702-61-3)

Conditions	Yield
Multi-step reaction with 4 steps 1: 3.54 g / acetonitrile / 7 h / 25 °C 2: 88 percent / dimethylformamide / 8 h / 25 °C 3: 82 percent / dimethylformamide / 25 °C 4: 70 percent / ceric ammonium nitrate / acetonitrile; H2O / 1 h / 0 - 25 °C View Scheme

7-[(2-chloroethoxy)methyl]guanine (146828-69-5) → 7-(2-Hydroxyethoxymethyl)guanine (91702-61-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 82 percent / dimethylformamide / 25 °C 2: 70 percent / ceric ammonium nitrate / acetonitrile; H2O / 1 h / 0 - 25 °C View Scheme

9-(triphenylmethyl)guanine (374678-33-8) → 7-(2-Hydroxyethoxymethyl)guanine (91702-61-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: 88 percent / dimethylformamide / 8 h / 25 °C 2: 82 percent / dimethylformamide / 25 °C 3: 70 percent / ceric ammonium nitrate / acetonitrile; H2O / 1 h / 0 - 25 °C View Scheme

2,9-diacetylguanine (3056-33-5) → 7-(2-Hydroxyethoxymethyl)guanine (91702-61-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1.) p-toluenesulfonic acid / 1.) AcOH, 2.) toluene, reflux, 16 h 2: 82 percent / aq. MeNH2 / 0.5 h / 80 °C View Scheme
Multi-step reaction with 2 steps 1: 22 percent / p-toluenesulfonic acid / 1.) 120-125 deg C, 2.) 150 deg C, 45 min 2: 82 percent / aq. MeNH2 / 0.5 h / 80 °C View Scheme

7-(2-Hydroxyethoxymethyl)guanine (91702-61-3) → 7-[(2-chloroethoxy)methyl]guanine (146828-69-5)

Conditions	Yield
With thionyl chloride In N,N,N,N,N,N-hexamethylphosphoric triamide at 20℃; for 24h;	61.9%

7-(2-Hydroxyethoxymethyl)guanine (91702-61-3) + methyl iodide (74-88-4) → 7-(2-Hydroxyethoxymethyl)-9-methylguaninium Hydroiodide (124321-53-5)

Conditions	Yield
In N,N-dimethyl-formamide at 20℃;	31%

N-ethyl-N-(2,3-dihydro-1,4-phthalazinedion-6-yl)-{4-[1,5-bis(4-N,N-dimethylaminophenyl)-5-(4-N-ethyl-N-(2,3-dihydro-1,4-phthalazinedion-6-yl)aminophenyl)-2,4-pentadienylidene]-2,5-cyclohexadien-1-ylidene}ammonium perchlorate (760974-67-2) + 7-(2-Hydroxyethoxymethyl)guanine (91702-61-3) → C61H63N13O7

Conditions	Yield
Stage #1: 7-(2-Hydroxyethoxymethyl)guanine With sodium hydride In dimethyl sulfoxide; mineral oil at 20℃; for 3h; Stage #2: N-ethyl-N-(2,3-dihydro-1,4-phthalazinedion-6-yl)-{4-[1,5-bis(4-N,N-dimethylaminophenyl)-5-(4-N-ethyl-N-(2,3-dihydro-1,4-phthalazinedion-6-yl)aminophenyl)-2,4-pentadienylidene]-2,5-cyclohexadien-1-ylidene}ammonium perchlorate In dimethyl sulfoxide; mineral oil at 20℃; for 2h;

Upstream product

• 3056-33-5 2,9-diacetylguanine 
• 374678-33-8 9-(triphenylmethyl)guanine 
• 146828-69-5 7-[(2-chloroethoxy)methyl]guanine 
• 890044-83-4 6-Trimethylsilanyloxy-9H-purin-2-ylamine 
• 73-40-5 2-amino-1,9-dihydro-6H-purin-6-one 
• 374678-34-9 7-[[2-(p-methoxyphenyloxy)ethoxy]methyl]guanine 
• 59278-00-1 2-acetoxyethyl acetoxymethyl ether 
• 108-24-7 acetic anhydride 
• 118-00-3 G 
• 91702-60-2 7-<(2-acetoxyethoxy)methyl>-N²-acetylguanine 

Relevant articles and documents

Antiviral compounds

This invention relates to purine compounds of formula (I): R1 is NH2 or OH; R2 is H or NH2; R3 is H or alkyl; each of m and n, independently, is 1, 2, 3, or 4; X is O, S, or NH; and Y is H, halogen, ORa, P(O)(ORa)2, or P(O)(ORa)(ORb), in which Ra is H, alkyl, aryl, heteroaryl, cyclyl, heterocyclyl, and Rb is wherein A is adenine, guanine, cytosine, uracil, or thymine; Rc is H or OH; Rd is H or alkyl; Re is H, alkyl, or 5-ethylidene-(3,4-dialkoxyl)-furan-2-one; provided that if R1 is NH2, R2 is H; and if R1 is OH, R2 is NH2.

Synthesis of 9-(2-hydroxyethoxymethyl)guanine (acyclovir) from guanosine

A convenient synthesis of 9-(2-hydroxyethoxymethyl)guanine (acyclovir) from guanosine by chemical transpurination was developed. The isomerization of the 7-isomer to the desired 9-isomer and the purification of the 9- isomer was achieved simply by concentration, heating and further crystallization.