Method for synthesizing multiple acrivastine impurities at once and application thereof
A one-time technology of Avastin, applied in the field of drug synthesis, can solve the problems of difficult synthesis, long time-consuming, low yield, etc., and achieve the effect of simple operation, mild and controllable conditions, and high purity
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Problems solved by technology
Method used
Image
Examples
Embodiment 1
[0050] Embodiment 1 The one-time synthesis of multiple double bond isomerization Avastin
[0051] Add 30mL of hydrochloric acid to 3.6L of purified water to prepare dilute hydrochloric acid of about 0.10mol / L, then add 0.54L of acetonitrile and 0.36L of tetrahydrofuran, mix well, add 2.5g of aclastine, stir to dissolve and transfer to two 2L beakers , react under direct sunlight at 10-30°C for 3 days, transfer the solution to a rotary evaporator, concentrate under reduced pressure at ≤75°C until the residue is about 0.1L, and then filter, and the mother liquor is purified by preparative chromatography (chromatographic column : Lichrospher C18, 30mm×250mm, 5μm, 10nm; mobile phase: 0.05mol / l sodium dihydrogen phosphate-acetonitrile-tetrahydrofuran (80:12:8)), collect the corresponding components, and concentrate under reduced pressure at ≤75°C Then add water to dissolve, adjust the pH to 6.5-7.5 with 0.05% sodium hydroxide solution to precipitate a solid, filter with suction, an...
Embodiment 2
[0052] Embodiment 2 One-time synthesis of multiple double bond isomerization Avastin
[0053] Add 0.5L of methanol to 5L of about 0.10mol / L disodium hydrogen phosphate solution, mix well, add 5g of Avastin, stir to dissolve, transfer to two 5L beakers, and place under direct sunlight for 10-20 ℃ for 5 days, transfer the solution to a rotary evaporator, concentrate under reduced pressure at ≤ 75 ℃ to a residue of about 0.1L and then filter, and purify the mother liquor by preparative chromatography (column: Lichrospher C18, 30mm×250mm, 5μm, 10nm Mobile phase: 0.02mol / L sodium dihydrogen phosphate-acetonitrile (80:20)), collect corresponding components, add water to dissolve after concentrating under reduced pressure at ≤75°C respectively, adjust the pH to 0.05% sodium hydroxide solution 6.5~7.5 precipitated solid, suction filtered and dried to obtain 250mg of (Z,E)-Arvastin (purity 95.5%), 580mg of (E,Z)-Arvastin (purity 97.2%), 100mg of (Z,E)-Avastatin (purity 94.8%).
Embodiment 3
[0054] Embodiment 3 One-time synthesis of multiple double bond isomerization Avastin
[0055] Add 0.05L dimethylformamide to 5L of about 0.10mol / L sodium dihydrogen phosphate solution, mix well, add 5g of Avastin, stir to dissolve, transfer to two 5L beakers, and place in direct sunlight React at 10-30°C for 5 days, transfer the solution to a rotary evaporator, concentrate under reduced pressure at ≤75°C until the residue is about 0.1L, then filter, and purify the mother liquor by preparative chromatography (chromatographic column: Lichrospher C18, 30mm×250mm , 5 μm, 10nm; mobile phase: 0.02mol / L disodium hydrogen phosphate-acetonitrile-isopropanol (80:15:5)), collect the corresponding components, concentrate under reduced pressure at ≤75°C, and then dissolve them in water. Adjust the pH to 6.5-7.5 with 0.01mol / L dilute hydrochloric acid solution to precipitate a solid, suction filter, and dry to obtain 80 mg of (Z, E)-Arvastin (purity 97.5%), 150 mg of (E, Z)-Arvastin Avasta...
PUM
Login to View More Abstract
Description
Claims
Application Information
Login to View More