BMS-911543 is a complex pyrrolopyridine investigated as a potential treatment for myeloproliferative disorders. The development of a short and efficient synthesis of this molecule is described. During the course of our studies, a Ni-mediated C-N bond formation was invented, which enabled the rapid construction of the highly substituted 2-aminopyridine core. The synthesis of this complex, nitrogen-rich heterocycle was accomplished in only eight steps starting from readily available materials.
The stability of the water-terminated Si(100)-2 × 1 surface in the 300-550 K temperature range is investigated with ultrahigh vacuum scanning tunneling microscopy experiments and density functional theory calculations. For temperatures below 450 K the surface is found to be stable from hydroxyl decomposition and surface oxidation. In the range of 450-550 K, new surface features associated with oxygen insertion into the silicon dimer bond are observed. It is found that the rate of hydroxyl decomposition and oxygen insertion does not follow simple first order kinetics with respect to the surface hydroxyl groups. Density functional theory calculations of oxygen insertion pathways point toward a catalytic effect of the dangling bonds and suggest that in the 450-550 K range the insertion events should predominantly occur next to unoccupied surface sites. A model is proposed where the dangling bonds diffuse along the dimer rows and promote hydroxyl decomposition. Kinetic Monte-Carlo simulations are used to compare the model with both experiments and density functional theory calculations, and an insertion activation barrier of 1.8 eV is found to give a good fit to the experimental data. On the basis of the findings, a strategy to increase hydroxyl group stability is demonstrated using water termination at cryogenic temperatures.
A mechanistic model for supersaturation and crystal growth during batch crystallization of organic solids from solutions containing multiple conformers is presented. The model is based on the approach of the right conformer (RC) which assumes that only one conformer participates in the surface integration step. The model is concerned with systems characterized by slow crystal growth and low supersaturation, a behavior favored when the RC is the minority species in solution. Crystal growth is assumed to occur via a step advance mechanism with a variable step advance velocity (VSAV). Model derivation indicated that when the approach of the RC applies, crystal growth is inversely proportional to crystal size. Lastly, model simulations predicted an exponential increase of maximum relative supersaturation with linear antisolvent addition rate. The simulation also allowed estimation of maximum addition rate below which secondary nucleation is minimized.
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