9‐Phenylphenanthrene

Mallory, Frank B.; Wood, Clelia S.

doi:10.1002/0471264180.os045.28

Cited by 1 publication

(1 citation statement)

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“…Large-Scale Synthesis of Intermediates 5 and 9. The high-yielding Green-Rowe oxidation procedure, [26][27][28] as used in the research synthesis of 4 (Scheme 1), was judged critical for scale-up: DSC measurements showed that deprotonation of 3 with potassium hydroxide in ethanol solution at 60 °C occurred at the onset temperature of the exothermic decomposition of the aci-nitroanion intermediate 13 29,30 (Scheme 2, estimated TMR < 30 min at 60 °C). Furthermore, the combination of ethanol and excess sodium hypochlorite is a source for ethylhypochlorite, which is both volatile (bp 36 °C) and explosive.…”

Section: Research Syntheses Of Pde472mentioning

confidence: 99%

Large-Scale Negishi Coupling as Applied to the Synthesis of PDE472, an Inhibitor of Phosphodiesterase Type 4D

Manley

Acemoglu

Marterer

et al. 2003

Org. Process Res. Dev.

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5-[2-Methoxy-5-(4-pyridinyl)phenyl]-2,1,3-benzoxadiazole (PDE472) is a selective inhibitor of the phosphodiesterase PDE4D isoenzyme, which is a recognised drug target for the treatment of asthma. Different synthetic routes to PDE472 were investigated, and the research synthesis was optimised to prepare a phase I batch on pilot-plant scale with the focus on the elimination or minimization of inherent process risks. An important refinement of the key Negishi aryl-aryl coupling involved preforming the arylpalladium complex, which was then added to the arylzinc intermediate. Residual palladium was removed from PDE472 via crystallization of the hemi-maleate salt, which afforded drug-substance containing <2 ppm Pd.

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Section: Research Syntheses Of Pde472mentioning

confidence: 99%