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Pazopanib, a multi-targeted tyrosine kinase inhibitor, is associated with cardiovascular adverse events, such as hypertension, cardiac dysfunction, and thromboembolism. However, symptomatic pazopanib-related bradycardia is uncommon. We herein report a case of symptomatic bradycardia of 35 beats per minute in a patient with solitary fibrous tumor/hemangiopericytoma (SFT/HPC) treated with pazopanib for 1 month. His heart rate recovered to a normal range soon after pazopanib cessation. He restarted pazopanib at a reduced dose, which was continued without SFT/HPC progression or bradycardia recurrence. This case highlights the possibility of bradycardia induced by pazopanib and the importance of monitoring the patient's heart rate.

TiCl 4 ÀEt 3 N or ÀBu 3 N reagent conducted a highly (Z)-stereoselective carbon homologation (dehydration type Ti-Claisen condensation) of alkyl a-heteroatom (halo and sulfonyloxy)-substituted acetates (XCH 2 CO 2 R) with alkyl formates (HCO 2 R) to afford various alkyl b-alkoxy-a-halo or sulfonyloxy-substituted acrylates (24 examples; 51%-91% yield). Stereoretentive Suzuki-Miyaura, Negishi, and Sonogashira cross-couplings using the obtained methyl b-methoxy-a-halo or sulfonyloxysubstituted acrylates proceeded smoothly to produce a variety of b-alkoxy-a-substituted acrylates in moderate to high yield (35 examples; 29%-99% yield). As a successful application, a 3-step straightforward synthesis of strobilurin A was performed utilizing the present reaction sequence (dehydration type Ti-Claisen condensation and Suzuki-Miyaura crosscoupling), wherein the geometry of the three consecutive olefins (2E,3Z,5E) was completely maintained. . Reported dehydration-type inter and intramolecular Ti-Claisen condensations. Scheme 2. (Z)-Stereoselective dehydration-type Ti-Claisen condensation of esters 1 and 4 with alkyl formates 2. Scheme 3. (Z)-Stereoretentive Suzuki-Miyaura, Negishi, and Sonogashira cross-couplings using acrylates 3 and 5.Scheme 4. (E)-Stereoselective dehydration-type Ti-Claisen condensation of octyl acetate with methyl formate 2 a.UPDATES