Toluene → 2-(Ethyloxy)-6-fluoro-4-{2-(methylamino)-6-[(3R)-3-(1-methylethyl)-4-morpholinyl]-4-pyrimidinyl}benzonitrile

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2,6-Difluoro-4-{2-(methylamino)-6-[(3R)-3-(1-methylethyl)-4-morpholinyl]-4-pyrimidinyl}benzonitrile (377 mg, 1.01 mmol) was azeotroped with toluene (2×15 mL). The residue was dissolved in 5 mL of DMF as a clear yellow solution. NaH (260 mg, 60% wt in mineral oil, 6.5 mmol) was weighted into a 50 mL 3-neck RB, to which under nitrogen was added ethanol (7.5 mL) portion-wise. The resulting clear solution was stirred at ambient temperature for 10 minutes. A portion of this solution (1.40 mL, 1.21 mmol of NaOEt, 1.2 equiv) was added to the above yellowish solution via syringe at room temperature under nitrogen in one portion. The resulting orange clear solution was stirred at room temperature for 20 hours. LCMS showed complete conversion. The mixture was concentrated in vacuo, and then pumped under vacuum to give a residue, which was taken up in 20 mL of water as a suspension. This suspension was sonicated briefly and filtered. The collected solids were dissolved in EtOAc (50 mL), and the resulting organic solution was washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. Purification of the resulting residue by silica gel column chromatography using gradient elution of 1% EtOAc in CHCl3 to 100% EtOAc gave the title compound (315 mg) as a yellowish residue. LC-MS (ES) m/z=400 [M+H]+.

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