Sodium Iodide → HCID 178523847, compound

Participants

Reaction Steps

A 25 mL round-bottomed flask containing a suspension of (S)-2-methoxy-N-((4-(trifluoromethyl)phenyl)(3-(trifluoromethyl)pyridin-2-yl)methyl)pyrimidine-5-carboxamide (Example 44) (0.094 g, 0.206 mmol) and sodium iodide, anhydrous (0.129 g, 0.861 mmol) in anhydrous MeCN (3.5 mL) was treated with chlorotrimethylsilane, redistilled (0.130 mL, 1.028 mmol). The resulting suspension was stirred at rt for 17.5 h. The reaction was concentrated on the rotary evaporator resulting in a gummy residue which was taken up in DCM (55 mL), H2O (25 mL), and 10% aqueous sodium thiosulfate (20 mL). The resulting mixture was transferred to a separatory funnel and after vigorous extraction the organic layer was separated, dried over anhydrous sodium sulfate, and concentrated to yield the product. The product thus obtained was dissolved in DMSO/MeOH (1/1) (3.5 mL) and loaded on a Gibson HPLC system for purification using a MeCN/H2O/0.1% TFA gradient and Phenomenex™ Gemini Axia-5μ C-18 column (150×30 mm). The solvent was removed from the pure fractions in the Genevac™ and the resulting product was dissolved in MeOH (3 mL), concentrated in the Genevac™, and dried under high vacuum to yield (S)-2-hydroxy-N-((4-(trifluoromethyl)phenyl)(3-(trifluoromethyl)pyridin-2-yl)-methyl)pyrimidine-5-carboxamide as an amorphous white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.30 (d, J=7.6 Hz, 1H), 8.93 (d, J=3.9 Hz, 1H), 8.80 (s, 2H), 8.27 (dd, J=8.0, 1.2 Hz, 1H), 7.75-7.70 (m, 2H), 7.64 (dd, J=7.9, 5.0 Hz, 1H), 7.56-7.50 (m, 2H), 6.76 (d, J=7.6 Hz, 1H). MS (ESI pos. ion) m/z: 443.1 (M+H).

Provenance & Evidence