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0 °C

A flask was charged with perfluorophenyl 4-(2-chloro-3′-fluoro-5-methoxy-[1,1′-biphenyl]-4-yl)quinazoline-7-sulfonate (Intermediate ZZZZZ; 0.060 g, 0.098 mmol), pyrimidin-4-amine (9.81 mg, 0.103 mmol), and THF (0.982 ml) and cooled to 0° C. LHMDS (1.0M in THF) (0.206 ml, 0.206 mmol) was added drop wise and the reaction was stirred for 30 minutes. The reaction was quenched with saturated ammonium chloride solution, diluted with ethyl acetate and washed with water. The aqueous layer was extracted with ethyl acetate, and the combined organic layers were dried with sodium sulfate, filtered, and concentrated. The material was purified via column chromatography (RediSep Gold 80 g, gradient elution 0-10% MeOH:DCM) to afford 4-(2-chloro-3′-fluoro-5-methoxy-[1,1′-biphenyl]-4-yl)-N-(pyrimidin-4-yl)quinazoline-7-sulfonamide (0.044 g, 0.084 mmol, 86% yield) as an -off-white solid. 1H NMR (400 MHz, DMSO-d6) δ=9.49 (s, 1H), 8.57 (s, 1H), 8.51 (d, J=1.6 Hz, 1H), 8.22 (d, J=6.9 Hz, 1H), 8.08 (dd, J=1.8, 8.8 Hz, 1H), 7.91 (d, J=8.9 Hz, 1H), 7.67 (s, 1H), 7.59 (dt, J=6.3, 8.1 Hz, 1H), 7.48-7.41 (m, 2H), 7.37-7.29 (m, 2H), 7.00 (d, J=5.0 Hz, 1H), 3.74 (s, 3H). m/z (ESI) 522.0 (M+H)+.

1. customThe reaction was quenched with saturated ammonium chloride solution
2. additiondiluted with ethyl acetate
3. washwashed with water
4. extractionThe aqueous layer was extracted with ethyl acetate
5. dry with materialthe combined organic layers were dried with sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated
8. customThe material was purified via column chromatography (RediSep Gold 80 g, gradient elution 0-10% MeOH:DCM)