This paper gives details of the analytical and numerical procedures used to solve the basic problem of the scattering of a plane electromagnetic wave by an axisymmetric raindrop. A nonperturbative solution is obtained by expanding the scattered and transmitted fields in terms of spherical vector wave functions, so that Maxwell's equations are satisfied exactly in the regions exterior and interior to the raindrop, and by combining point matching with least‐squares fitting to satisfy the boundary conditions on the surface of the raindrop with sufficient accuracy. Numerical results are presented for scattering by oblate spheroidal raindrops, with eccentricity depending on (and increasing with) drop size, for two orthogonal polarizations of the incident wave. The calculations were made at 4, H, 18.1, and 80 GHz, in the case in which the direction of propagation of the incident wave is perpendicular to the axis of symmetry of the raindrop, which is of interest for terrestrial microwave relay systems. At 30 GHz, the calculations were also made for the case in which the angle between the direction of propagation and the axis of symmetry is 70° and 50°, since different elevation angles are of interest for satellite systems. These basic results were summed earlier over the drop‐size distribution to calculate the differential attenuation and differential phase shift caused by rain, which are of importance in the investigation of cross polarization in radio communication systems. We also derive the first‐order perturbation approximation to the scattering by axisymmetric raindrops that are nearly spherical, which generalizes Oguchi's results for spheroidal raindrops with small eccentricity. Some simplifications that may be made in his formulas are pointed out. The perturbation results serve as a useful check on the least‐squares‐fitting procedure applied to spheroidal raindrops with small eccentricity. In addition, considerable improvement is obtained in the closeness of the perturbation results to the least‐squares‐fitting ones, in particular for the larger drop sizes, by perturbing about an equivolumic spherical raindrop, with appropriate perturbation parameter, rather than perturbing about an inscribed spherical raindrop, as did Oguchi. Similar comparisons were also made earlier for the rain‐induced differential attenuation and differential phase shift, and these quantities were calculated approximately at frequencies up to 100 GHz, using the results corresponding to perturbation about the equivolumic spherical raindrop. The perturbation results are obtained quite inexpensively, whereas the least‐squares‐fitting procedure is very costly.

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The paper gives the results of calorimetric measurements of the heat capacities of solid and liquid CH4 and CD4, the heats of fusion of both substances and the heat of vaporization of CD4. The results for the solids, which extend from 2.3°K to the triple points, are analyzed in some detail. In order to account for the apparent zero-point entropies of both CH4 and CD4 quantitatively, it is necessary to recognize the existence of different nuclear spin species (as with ortho and para hydrogen) and to say that, as T approaches 0°K, each species tends to occupy its lowest available molecular energy level. No conversion between the different species has been observed. The relevance of these findings to the usual applications of the third law of thermodynamics is discussed. The thermal transitions which occur in solid CH4 and CD4 (as well as in the partially deuterated methanes) have also been examined and an attempt made to correlate the thermodynamic results with information derived from other experiments (e.g., spectroscopic, neutron scattering) and from theory. While correlations are possible, the fundamental causes of the transitions can still not be established.

AZD6738 is currently being tested in multiple phase I/II trials for the treatment of cancer. Its structure, comprising a pyrimidine core decorated with a chiral morpholine, a cyclopropyl sulfoximine, and an azaindole, make it a challenging molecule to synthesize on a large scale. We describe the evolution of the chemical processes, following the manufacture of AZD6738 from the initial scale-up through to multikilos on plant scale. During this evolution, we developed a biocatalytic process to install the sulfoxide with high enantioselectivity, followed by introduction of the cyclopropyl group first in batch, then in a continuous flow plate reactor, and finally through a series of continuous stirred tank reactors. The final plant scale process to form AZD6738 was operated on 46 kg scale with an overall yield of 18%. We discuss the impurities formed throughout the process and highlight the limitations of this route for further scale-up.

Hydropyrans are important structural units found in synthetic and natural ionophores and polyether macrolides. 1,2 Recent efforts directed at hydropyran synthesis include anionic cyclization, 3 cationic cyclization, 4 radical cyclization, 5 hetero-Diels-Alder cycloaddition, 6 dioxanone Claisen rearrangement, 7 and ring-closing metathesis of enol ethers. 8 To date, however, there has been no demonstration of a stereochemically general method for the synthesis of dihydropyrans of general structure 1 (eq 1).We envisioned the tandem sequence of glycolate Claisen rearrangement 9 /ring-closing metathesis 10 as providing such a protocol. Diene metathesis substrate 2 contains an R-alkoxy-γ,δ-unsaturated ester, known to be available via a glycolate Claisen rearrangement 9 of substrates such as 3. Merger of two allylic alcohol subunits with a bromoacetic acid linchpin would afford this glycolate Claisen substrate. Stereogenicity at the indicated centers in 1 would follow in a predictable fashion from the indicated stereogenic centers in the allylic alcohol components 4 and 5. This convergent and stereochemically general synthesis of substituted hydropyrans is illustrated herein for cis-and trans-3-substituted dihydropyran-2-carboxylates and for all four diastereomeric permutations of 3,6-disubstituted dihydropyran-2carboxylates.A simple example in a racemic series is illustrated in Scheme 1. O-Alkylation of allyl alcohol with bromoacetic acid (2 equiv of NaH, THF, 66°C) gave 6, which afforded glycolate Claisen substrate 7 upon Steglich-Hassner 11 coupling with (E)-3-penten-2-ol. Subjection of the ester to standard Ireland-Claisen conditions 12 effected the [3,3]-(1) (a) Burke, S. D.; Porter, W. J.; Rancourt, J.; Kaltenbach, R. F. Kan, T.; Yanagiya, M.; Shirahama, H.; Matsumoto, T. Tetrahedron Lett. 1987, 28, 5665. (d) Faivre, V.; Lila, C.; Saroli, A.; Doutheau, A. Tetrahedron 1989, 45, 7765. (e) Nicolaou, K. C.; Prasad, C. V. C.; Somers, P. K.; Hwang, C.-K. (13) (a) see ref 9a. (b) Typical procedure: A solution of glycolate ester in THF is added slowly to a solution of freshly prepared LDA at -100°C.After the solution is stirred at -100°C for 15 min, the supernatant of a centrifuged 1:1 (v/v) mixture of TMSCl and triethylamine is added. The mixture is allowed to warm to ambient temperature and stirred overnight. The silyl ester is hydrolyzed by treatment with either 1 M NaOH or 1 M HCl. The acid is isolated by acid/base extractions. Scheme 1 3160sigmatropic shift via the bracketed silyl ketene acetal. 13 Chelation control over enolate geometry and π-facial preferences dictated by the chairlike transition state produce, after esterification, the metathesis substrate 8b with the relative stereochemistry shown for the major isomer (diastereoselectivity 6:1). Exposure of 8b to [RuCl 2 (dCHPh)(PCy 3 ) 2 ] (9) 14 in benzene (60°C, 0.5 h) or CH 2 Cl 2 , (23°C, 3 h) gave cis-3-substituted dihydropyran-2-carboxylate 10 in 73% yield.Further examples of metathesis substrate preparation via the glycolate Claisen rearrangement are sum...