Dichloromethane → HCID 59548287, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 1-(methylsulfonyl)piperazine (13.34 mg, 0.081 mmol, Apollo), 1-(6-(6-amino-2-methylpyrimidin-4-yl)-5-(5-fluoro-6-methoxypyridin-3-ylamino)pyrazin-2-yl)ethanone (15 mg, 0.041 mmol) and titanium(iv) isopropoxide (0.048 mL, 0.162 mmol, Aldrich, St. Louis, Mo.) in tetrahydrofuran (0.5 mL) was stirred at 75° C. for 25 h. The mixture was cooled down to 20° C. and CH2Cl2 (1 mL) was added followed by sodium triacetoxyborohydride (34.4 mg, 0.162 mmol). The reaction mixture was stirred at room temperature for 5 h. The reaction mixture was diluted with ammonia (3 mL, 30% in water) and extracted with CH2Cl2 (2×20 mL). The combined organic extracts were washed with saturated NaCl (5 mL) and dried over Na2SO4. The solution was filtered and concentrated in vacuo to give the crude material as a yellow solid. The crude product was purified by silica gel chromatography eluting with 5% MeOH/CH2Cl2 to give 6-(3-(5-fluoro-6-methoxypyridin-3-ylamino)-6-(1-(4-(methylsulfonyl)piperazin-1-yl)ethyl)pyrazin-2-yl)-2-methylpyrimidin-4-amine (4.8 mg, 9.27 μmol, 23% yield). 1H NMR (300 MHz, CDCl3) δ 1.44 (d, J=6.58 Hz, 3H) 2.46-2.69 (m, 7H) 2.77 (s, 3H) 3.23 (t, J=4.24 Hz, 4H) 3.55 (q, J=6.77 Hz, 1H) 4.03 (s, 3H) 5.42 (s, 2H) 8.04 (d, J=2.19 Hz, 1H) 8.20-8.37 (m, 2H) 8.70 (d, J=1.90 Hz, 1H) 11.90 (s, 1H). m/z (ESI, +ve ion) 518.2 (M+H)+.

Provenance & Evidence