Adefovir synthesis

6synthesis methods

Product Name:Adefovir
CAS Number:106941-25-7
Molecular formula:C8H12N5O4P
Molecular Weight:273.19

[[2-(6-Amino-9H-purin-9-yl)ethoxy]methyl]phosphonic acid diethyl ester

116384-53-3

106941-25-7

The general procedure for the synthesis of ((2-(6-amino-9H-purin-9-yl)ethoxy)methyl)phosphonic acid from diethyl ((2-(6-amino-9H-purin-9-yl)ethoxy)methyl)phosphonate is as follows: a 10L three-necked flask was fitted with a mechanical stirrer and thermometer. 1.4 kg (4.26 mol) of diethyl ((2-(6-amino-9H-purin-9-yl)ethoxy)methyl)phosphonate (Intermediate III) and 8 L of acetonitrile were sequentially added to the flask, followed by the addition of trimethylmethylsilyl bromide. The reaction mixture was stirred at room temperature for 1 hour and then heated to reflux for 2 hours. Upon completion of the reaction, the solvent was removed by distillation under reduced pressure. To the residue, 5 L of water was added, the mixture was stirred and the pH was adjusted to 3.2-3.4 with 25% sodium hydroxide solution. the mixture was heated to reflux for 2 hr. Upon completion of the reaction, the reaction mixture was cooled to room temperature and filtered. The filter cake was purified by aqueous recrystallization and dried under vacuum at 70 °C for 8 h. 9-(2-phosphomethoxyethyl)adenine was obtained as a white crystalline solid powder with a yield of 1.07 kg, 86.3% yield and melting point of 298-300 °C.

116384-53-3 Synthesis

116384-53-3
177 suppliers
$27.00/1g

106941-25-7
340 suppliers
$5.00/250mg

Yield:106941-25-7 86.3%

Reaction Conditions:

Stage #1:[[2-(6-amino-9H-purine-9-yl)ethoxy]methyl]phosphonic acid diethyl ester with trimethylsilyl bromide in acetonitrile at 20; for 3 h;Large scale;
Stage #2: with sodium hydroxide in water for 2 h;Reflux;Large scale;

Steps:

4 Preparation of 9-(2-phosphomethoxyethyl) adenine (Intermediate IV, PMEA)
A mechanical stirrer and a thermometer were installed in a 10 L three-necked flask. To this was added 1.4 kg (4.26 mol) of intermediate III, Trimethylsilyl bromide in this orderAnd 8 L of acetonitrile were added thereto. The mixture was stirred at room temperature for 1 hour and heated to reflux for 2 hours. After completion of the reaction, the solvent was distilled off under reduced pressure, 5 L of water was added, and the mixture was stirred and adjusted to pH 3.2 to 3.4 with 25% sodium hydroxide. The mixture was heated to reflux for 2 hours. After completion of the reaction, the reaction mixture was cooled to room temperature and filtered. The cake was recrystallized once from water and vacuum dried at 70 ° C for 8 hours. 9- (2-phosphomethoxyethyl) adenine as a white crystalline solid powder 1.07kg, Μρ: 298 ~ 300 ° (3, yield 86.3%.

References:

Suzhou Erye Pharmaceutical Co., Ltd.;ZHANG, JIAN;ZHU, WEI;YAO, CHANYAN;CHEN, XUEWEN CN104387421, 2016, B Location in patent:Paragraph 0032-0034

FullText

707-99-3 Synthesis