Sodium Bicarbonate → HCID 59548318, compound

Participants

Reaction Steps

To a slurry of methyl 5-(4-amino-6-methyl-1,3,5-triazin-2-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)nicotinate (0.400 g, 1.038 mmol) and titanium(iv) isopropoxide (0.365 mL, 1.246 mmol) in 8 mL THF at ambient temperature was added ethylmagnesium bromide 1.0 M solution in THF (5.61 mL, 5.61 mmol) over 2-3 min. The reaction became dark brown and warm, with bubbling. The reaction was cooled briefly with an ice bath and then allowed to stir at ambient temperature. After 1 h, an additional 2.4 equiv 1.0 M ethylmagnesium bromide in THF was added at ambient temperature. After 30 min, the reaction was cooled to 0° C. and quenched with ice and sat'd aq. NH4Cl. The reaction was partitioned between sat'd aqueous NH4Cl and DCM. The aqueous layer was extracted with DCM 3 times, and ethyl acetate once, and the combined organics were dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. Purification by RPHPLC (Gradient, Acetonitrile+0.1% TFA/water+0.1% TFA) provided 0.070 g of a sticky orange film. The material was treated with sat'd aq. NaHCO3 and 10% iPrOH/DCM. The aq. layer was extracted 3×10% iPrOH/DCM and combined organics dried over sodium sulfate, filtered, and concentrated in vacuo to give 1-(5-(4-amino-6-methyl-1,3,5-triazin-2-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)cyclopropanol (0.027 g, 0.070 mmol, 7% yield) as a yellow solid. m/z (ESI, +ve ion) 384 (M+H)+. 1H NMR (400 MHz, d6-DMSO) δ 11.90 (s, 1H), 8.82 (d, J=2.5Hz, 1H), 8.29-8.48 (m, 2H), 8.20 (d, J=2.5 Hz, 1H), 7.91 (br. s., 1H), 7.75 (br. s., 1H), 6.03 (s, 1H), 3.93 (s, 3H), 2.44 (s, 3H), 1.04-1.13 (m, 2H), 0.86-0.98 (m, 2H).

Provenance & Evidence