Pemetrexed synthesis
- Product Name:Pemetrexed
- CAS Number:137281-23-3
- Molecular formula:C20H21N5O6
- Molecular Weight:427.41
![N-[4-[2-(2-Amino-4,7-dihydro-4-oxo-3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic acid 1,5-diethyl ester 4-methylbenzenesulfonate](/CAS/GIF/165049-28-5.gif)
165049-28-5
137281-23-3
The general procedure for the synthesis of pemetrexed disodium salt from (S)-2-(4-(2-(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl)benzamido)pentanedioic acid diethyl ester 4-methylbenzenesulfonate is as follows: 1. Preparation of pemetrexedic acid (Eq. 2): a. Add 1 L of a 1N aqueous NaOH solution to the reactor and cool to 5-15°C. b. To the cooled NaOH solution, slowly add 143 g of the compound of Formula 3 prepared in Example 1, maintaining the temperature at 5-15°C. c. The reaction mixture was stirred at 5-15°C for 2 hours, followed by filtration (HPLC purity: 99.8%). d. 2L of EtOH was added to the filtrate followed by slow dropwise addition of 2N HCl aqueous solution at 5-15°C to adjust the pH to 3.0. e. The crystalline mixture formed was stirred at 40-50°C for 1 hr and then filtered at 40°C. f. The filtered product was washed with 2 L of pure water followed by 1 L of EtOH. g. Dissolve the washed product in 4L of EtOH/pure water (1:1, v/v) and stir at 40-50°C for 1 hour. h. Cool to room temperature and filter, wash with 2L of pure water and then with 1L of EtOH. i. The product was dried under vacuum at 40-45 °C for 16 h to give 88 g of pemetrexedic acid as a white solid (yield: 95%, HPLC purity: 99.9%, individual impurity content: not mentioned). ii.
165049-28-5
161 suppliers
$7.00/250mg
137281-23-3
339 suppliers
$12.00/250mg
Yield:137281-23-3 95%
Reaction Conditions:
Stage #1:pemetrexed diethyl ester p-toluenesulfonic acid salt with sodium hydroxide in water at 5 - 15; for 2 h;
Stage #2: with hydrogenchloride in ethanol;water; pH=3 at 5 - 50; for 1 h;
Steps:
2 Preparation of Pemetrexed diacid (Formula 2)
Preparation of Pemetrexed diacid (Formula 2) (0081) In a reactor, 1 L of IN NaOH aqueous solution was added, and 143 g of the compound of formula 3 prepared in Example 1 was added thereto at 5-15° C. After stirring at 5-15° C. for 2 hours, the mixture was filtered (HPLC purity: 99.8%). To the filtered solution, 2 L of EtOH was added, and 2N HCl aqueous solution was slowly added thereto dropwise at 5-15° C. to adjust pH to 3.0. The formed crystalline mixture was stirred at 40-50° C. for 1 hour and filtered at 40° C. The filtered product was washed with 2 L of purified water, and further washed with 1 L of EtOH. The filtered product as obtained was added to 4 L of EtOH/purified water (1:1, v/v), and the mixture was stirred at 40-50° C. for 1 hour, and cooled and filtered at room temperature. The filtered product was washed with 2 L of purified water, further washed with 1 L of EtOH, and dried under vacuum at 40-45° C. for 16 hours to obtain 88 g of pemetrexed diacid as white solid (Yield: 95%, HPLC purity: 99.9%, individual impurity content:
References:
SAMYANG BIOPHARMACEUTICALS CORPORATION;KIM, Young Min;KIM, Moon Suk;KIM, Seong Ho;CHO, Jin Suk US2016/214987, 2016, A1 Location in patent:Paragraph 0081
1118-89-4
449 suppliers
$6.00/5g
137281-23-3
339 suppliers
$12.00/250mg