Reference of 155405-80-4, As we all know, there are many different methods for the synthesis of a compound, and people can choose the synthesis method that suits their own laboratory according to the actual situation. 155405-80-4, name is Methyl 4-(2-(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl)benzoate, molecular formula is C16H16N4O3, The compound is widely used in many fields, so it is necessary to find a new synthetic route. The downstream synthesis method of this compound is introduced below.
The current synthetic route for the preparation of Pemetrexed IM8 starts with an aldol-condensation reaction of Methyl-4-formylbenzoate (SM1 ) with 1 ,1- Dimethoxyacetone (SM2) to give Pemetrexed IM1a. As Pemetrexed IM1a irreversibly converts to its aldol-addition product Pemetrexed IM1 b under reaction conditions the reaction mixture is directly submitted to hydrogenation (i.e. without isolation of Pemetrexed IM1a) over Pd/C to give Pemetrexed IM2. As under the hydrogenation conditions not only the double- bond of IM1a is hydrogenated but also some amount of Pemetrexed IM2 is converted to Pemetrexed IM3 (hydrogenation of the carbonyl function to the corresponding secondary alcohol) a solution of NaBH4 is added to the reaction mixture to ensure complete conversion to Pemetrexed IM3. The Pd- catalyst is removed by filtration and the reaction mixture is extracted with toluene. The combined organic layers are evaporated to give crude Pemetrexed IM3 as oil. This oil is dissolved in THF and the alcohol functionality is converted to a mesylate using MsCI and NEt3. The salts are removed by filtration, glacial acetic acid is added and THF is removed by distillation. Upon addition of water Pemetrexed IM4 crystallizes and is isolated by filtration. The dried Pemetrexed IM4 is dissolved in glacial acetic acid and gaseous HCI is added to cleave the dimethoxy acetale and liberate the aldehyde functionality of Pemetrexed IM5. Upon complete deprotection a solution of 2,6-diamino-4-hydroxypyrimidine in aq. NaOH and acetonitrile is added. Upon complete conversion the crystallized Pemetrexed IM6 is isolated by filtration. The saponification of the methyl ester of Pemetrexed IM6 to Pemetrexed IM7 is done using aqueous NaOH. Upon addition of aq. HCI first the Na-salt of Pemetrexed IM7 crystallizes from the reaction mixture. The salt is isolated by filtration, purified by slurry in a mixture of MeOH and water and then converted to Pemetrexed IM7 by pH adjustment in water using aq. HCI. Dried Pemetrexed IM7 (water content not more than 6.0%) is dissolved in DMF, activated using 1 ,1-carbonyldiimidazolide (CDI) and then reacted with dimethyl-L-glutamate hydrochlorid to give, upon addition of water and filtration, crude Pemetrexed IM8. This intermediate is purified by tosylate salt formation, followed by recrystallization and liberation to give pure Pemetrexed IM8. Starting with the saponification of Pemetrexed IM8 the preparation of different solid forms of Pemetrexed Disodium can be achieved. Methods for Preparing Pemetrexed Disodium Form IV and Investigation of its Stability
According to the analysis of related databases, 155405-80-4, the application of this compound in the production field has become more and more popular.
Reference:
Patent; AZAD PHARMACEUTICAL INGREDIENTS AG; ALBRECHT, Uwe, Jens; HELMBOLDT, Hannes; NIKOLAEV, Vsevolod, Valiervich; WO2011/64256; (2011); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia