* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Production of the drug substance Gly-T3 ' HCl was performed as a one-pot reaction inside a 20-gallon glass lined reactor. To limit exposure of the workers to the potent material, the starting reagent T3 was prepared as a slurry in THF inside an EPO <DP n="44"/>isolator. The resulting slurry was then transferred to the 20-gallon reactor through a Teflon line. Subsequently, Boc-Gly-OSu was dissolved in THF, transferred to the 20-gallon reactor and then DIEA was dissolved in THF, and also transferred to the 20-gallon reactor. The suspension was stirred for 15 hours, at ambient temperature and became a clear solution. In process testing by HPLC (% AUC) of the collected sample after 15 hours showed a purity of 98.5 % for the desired compound, Boc- Gly-T3. The reaction was then quenched by adding water and the THF was removed by distillation. The solvent, TBME was then added and the batch was allowed to stir overnight at 5 to 10 0C. The solution was acidified by a 20 % aqueous Na2SO4ZNaHSO4 buffer solution. The product was extracted in TBME and the organic layers were combined in a 60 L Pope tank and dried with Na2SO4. The dried solution was then filtered through a 0.22 mum filter, charged into the 20- gallon reactor and stirred overnight at 15 0C. The TBME was removed by distillation, followed by IPAc chases (continuous feed), while the batch stirred overnight at 15 0C. The intermediate was Boc deprotected by pressurizing the 20- gallon reactor headspace with 30 psi HCl gas for 3 hours and 30 minutes. The obtained precipitate was filtered inside the isolator, washed with IPAc, and dried for 110 hours inside a vacuum oven at 35 0C. In process testing by GC showed the presence of 6.13 % residual IPAc. Therefore, the solids were hydrated (water displacement) for approximately 24 hours and dried until constant weight, in a vacuum oven for 50 hours at 35 0C. The material was packaged in glass amber bottles, which were put in polyethylene bags and stored at - 20 0C with desiccants.
O-[3-iodo-4-(sulfooxy)phenyl]-3,5-diiodo-L-tyrosine sodium salt[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
62%
3,5-diiodo-o-(4-hydroxy-3-iodophenyl)-L-tyrosine (100 g; 0.154 mol) was suspended in DMAC (2.0 L) under nitrogen atmosphere and stirred vigorously to avoid solid precipitation. After cooling to-5 C,While maintaining a temperature of -5 - 5 C, CSA (142.2 g; 1.229 mol) in 40 minutes at the end of the addition, the cooling was stopped and the reaction mixture was left under stirring for about 4 hours. The reaction mixture was added to a stirred aqueous solution of sodium carbonate (335.5 g; 4.5 liters in water) over a period of 1.5 hours, and precipitation of crystalline solids was observed as a mixture of inorganic salts from the resulting solution over time at the end of the addition, After filtering off the solids, the resulting solution was purified on an Amberlite XADTM 1600 by eluting with a water / acetone mixture with reduced polarity, and the eluate was collected in the flasks The product with the appropriate purity level The solvent was distilled off under reduced pressure to a concentration of 10 g / kg and the pH of the suspension was adjusted to 6.2 with HCl 1 N. The suspension was further diluted to a solids and residual water ratio of about 1: 3 The residue was treated with acetone for 2 hours under cooling and then filtered off and washed with acetone The product was dried at 40 C. under reduced pressure to give 74 g of T3S as a white solid, Yield of salt group: 62%.
3,5-diiodo-N-[[(carboxymethyl)[2-[(carboxymethyl)[2-[bis(carboxymethyl)amino]ethyl]amino]ethyl]amino]acetyl]-O-[3-iodo-4-(sulfooxy)phenyl]-l-tyrosine[ No CAS ]
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
120K+ Compounds
Competitive Price
1-2 Day Shipping
