Acetyl chloride → Tert-butyl 4-{[2-({3-(acetylamino)-5-[2-(1-hydroxycyclobutyl)-1,3-thiazol-5-yl]phenyl}amino)pyrimidin-4-yl]oxy}piperidine-1-carboxylate

Participants

Reaction Steps

At 0° C., the product from Step 3 (40 mg, 0.074 mmol) in DCM (0.4 mL) was added to acetyl chloride (6.34 μL, 0.089 mmol) and triethylamine (15.53 μL, 0.111 mmol) and the reaction was aged for 1 h. The mixture was then purified directly by column chromatography on silica gel (30-100%, ethyl acetate: 10:1 methanol in hexanes) to afford tert-butyl 4-{[2-({3-(acetylamino)-5-[2-(1-hydroxycyclobutyl)-1,3-thiazol-5-yl]phenyl}amino)pyrimidin-4-yl]oxy}piperidine-1-carboxylate (28 mg, 65% yield). Example 109(1). MS ESI: [M+H]+ m/z 581.3. 1H NMR (600 MHz, CDCl3): δ 8.10 (d, J=6.0 Hz, 1H); 7.90 (s, 1H); 7.76 (s, 1H); 7.65 (br s, 1H); 7.53 (s, 1H); 7.11 (s, 1H); 6.14 (d, J=6.0 Hz, 1H); 5.25 (m, 1H); 3.67 (m, 2H); 3.12 (br s, 2H); 2.64 (m, 2H); 2.43 (m, 2H); 2.13 (s, 3H); 1.92 (m, 4H); 1.66 (m, 2H); 1.43 (s, 9H). rhSYK activity=++

Provenance & Evidence