2,4-Dichloropyridine → N-(4-chloro-2-pyridinyl)-1,3-oxazol-2-amine

Temperature

100 °C

Palladium(II) acetate (11.38 mg, 0.05 mmol) was added in a single portion to a degassed solution of 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (44.0 mg, 0.08 mmol), oxazol-2-amine (85 mg, 1.01 mmol), cesium carbonate (768 mg, 2.36 mmol),2,4-dichloropyridine (0.109 mL, 1.01 mmol), dioxane (4 mL) and DMSO (0.8 mL) and the resulting mixture was heated at 100 °C for 16 hours under a nitrogen atmosphere. Note: the reaction mixture was degassed by first combing the reagents (with the exception of Pd((OAc)2), sealing the vessel and carrying out three pump- purge cycles (vac-nitrogen). Dioxane was then added to this mixture via syringe, followed by the Pd(OAc)2 in a single portion and the vessel was heated for the required time as above. Solvent boiled dry from reaction overnight. Only DMSO remained. **Crude proton NMR shows mainly dichlorpyridine starting material and the 2-aminooxazole starting material was absent**. Crude LCMS indicates that a product of the required mass is present. The crude product was purified by flash chromatography on C-18 modified silica, elution gradient 0 to 100% MeCN in water with basic modifier (1% ammonium hydroxide). Pure fractions were evaporated to dryness to afford N-(4-chloropyridin-2-yl)oxazol-2-amine (22.00 mg, 11.10 %) as a pale yellow residue. The product isolated, although impure, looks like the required product based on LCMS. The 1H NMR of the purified material is in D6-DMSO here and so not directly comparable with previous spectra in CDCl3. Conclusion: This may be worth pursuing (i.e. adding DMSO to aid solubility) based on the slightly increased yield. **Revision: Required product not isolated, spectral analysis of isolated sample does not match those of authentic samples of the coupled product** .

ORD record

ord-5dfaf464504c42b7bafec75259e5a214

Source dataset

750 AstraZeneca ELN dataset

Original link

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