289617-98-7Relevant articles and documents
Preparation method of 2-bromo-5-iodo-benzyl alcohol
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, (2021/08/11)
The invention relates to the technical field of organic synthesis, and discloses a preparation method of 2-bromine-5-iodine-benzyl alcohol, which comprises the following steps: S1, o-benzylamine, a phase transfer catalyst, ammonium bicarbonate and an iodination reagent are subjected to iodination reaction to generate 2-methyl-4-iodoaniline; S2, the 2-methyl-4-iodoaniline is subjected to a diazotization reaction and a bromination reaction, and 2-bromine-4-iodobenzene is generated; S3, the 2-bromine-4-iodobenzene reacts with an initiator and N-bromosuccinimide, so as to generate 2-bromine-4-iodobromomethyl benzene; and S4, the 2-bromine-4-iodine bromomethyl benzene reacts with alkali, so as to generate the 2-bromine-5-iodine-benzyl alcohol. The preparation method disclosed by the invention is simple in process operation, few in three wastes and beneficial to industrial production; and no isomer is generated in the iodinated product, reduction of lithium aluminum hydride is not needed, and the problem of high operation risk caused by a large amount of hydrogen generated during reduction of lithium aluminum hydride can be effectively avoided.
A re-examination of the difluoromethylenesulfonic acid group as a phosphotyrosine mimic for PTP1B inhibition
Hussain, Munawar,Ahmed, Vanessa,Hill, Bryan,Ahmed, Zaheer,Taylor, Scott D.
, p. 6764 - 6777 (2008/12/22)
Protein tyrosine phosphatase 1B (PTP1B) is involved in the down-regulation of insulin signaling and is a well-validated therapeutic target for the treatment of diabetes and obesity. Key to the design of potent inhibitors of PTP1B is a moiety that effectively mimics the phosphate group of the natural phosphotyrosine substrate. Difluoromethylsulfonomethylphenylalanine (F2Smp) is one of the best monoanionic pTyr mimics reported to date. However, the difluoromethylenesulfonic acid (DFMS) group as a phosphate mimic has not been carefully evaluated in the context of a non-peptidyl platform. Here we present a careful examination of the DFMS group as a phosphate mimic. This was achieved by first constructing an analog of a previously reported high affinity, non-peptidyl PTP1B inhibitor (compound 2, IC50 = 8 nM) in which a difluoromethylenephosphonic acid group is replaced with the DFMS moiety (compound 6). We also report the synthesis of its non-fluorinated methylenesulfonic analog (compound 7), as well as two other derivatives in which a distal sulfonamide moiety is replaced with a difluoromethylenesulfonamide group (compounds 8 and 9). Compounds 2 and 6-9 were examined as PTP1B inhibitors. Replacing the distal sulfonamide moiety with a difluoromethylenesulfonamide group had only a modest effect on inhibitor potency. However, compound 6 was approximately a 1000-fold poorer inhibitor than compound 2. Most significantly, inhibition studies with compound 7 and a peptide bearing sulfonomethylphenylalanine revealed that the fluorines have little effect on the potency of the DFMS-bearing inhibitors. This is in contrast to a previous assumption that the fluorines in DFMS-bearing inhibitors contributed significantly to their potency. This may in part explain the large difference in potency between the DFMS and DFMP-bearing compounds. These results also demonstrate that sulfonomethylphenylalanine, a pTyr mimic that is readily constructed, is a relatively good pTyr mimic in comparison to most others that have been reported when examined in the context of the DADE-X-LNH2 peptide platform.
Porous siloxane linked phenylacetylene nitrile silver salts from solid state dimerization and low polymerization
Kiang,Gardner, Geoffrey B.,Lee, Stephen,Xu, Zhengtao
, p. 6871 - 6883 (2007/10/03)
Three 3-fold symmetric rigid backbone phenylacetylene nitrile molecules have been prepared to which one to six hydroxy side chains have been attached. These molecules were cocrystallized with silver(I) trifluoromethanesulfonate (triflate) to form microcrystalline porous solids. X-ray powder data show that all three crystal structures are isotypic to the crystal structures found in previous single crystal studies on related systems. Structural models based on these earlier single crystal structures have theoretical powder patterns in reasonable agreement with the experimentally observed patterns. These crystalline materials were allowed to react with silyl triflates. 1H NMR and X-ray powder studies show that the silyl triflate groups react with the alcohol terminated side chains to form siloxane linkages with retention of the initial crystal structure. In the case of 1,3,5-tris(4-((4-cyanophenyl)ethynyl)-2-((4-hydroxybutoxy)methyl) phenylethynyl)benzene, a phenylacetylene nitrile molecule with three alcohol side chains, the introduction of di-tert-butylsilyl bis(trifluoromethanesulfonate) resulted in the formation of low polymers with average weight molecular weight of 7 x 104. This polymerized material shows increased chemical robustness in contrast to the unpolymerized material. It is stable in a variety of solvents, including overnight exposure to boiling water. Exchange experiments with toluene show that this final material is still porous.
