During synthesis, the solid phase carrier is filled into the synthesis column, and all reactions during the synthesis process are carried out within the column. According to the synthesis process, each base needs to undergo four steps of reaction: deprotection → coupling → oxidation (or vulcanization) → capping. The reagents used in the above four steps of reaction include dichloroacetic acid (DCA), 5-ethylthiotetrazolium (ETT) or 4.5 dicyanoimidazole (DCI), iodine, xanthan hydride (XH) or phenylacetyl disulfide (PADS), 1-methylimidazole, acetic anhydride, and 2.6-dimethylpyridine. These reagents are all dissolved in dichloromethane, acetonitrile, or pyridine. After each step of reaction, the residual reagents are washed with 2-4 times the column volume of acetonitrile. Each completion of four steps of reaction is called a cycle, which is repeated until the product sequence is synthesized. Finally, cyanoethyl is removed with diethylamine (DEA) or triethylamine (TEA), and the column volume is washed 2-4 times with acetonitrile again. Acetonitrile, often used as a solvent in the preparation of various synthetic reagents, has a good dissolution effect on various reagents and can rinse off residual synthetic reagents. The risk of reagent residue or product residue is relatively low. The synthesizer has a separate risk assessment report on cleaning validation, as shown in RAR-AMD-001 "OligoProcess Synthesizer Cleaning Validation Risk Assessment Report".
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