反应详情

温度

130 °C

(4-Amino-10-aza-tricyclo[6.3.2.0*2,7*]trideca-2,4,6-trien-10-yl)-acetonitrile (30 mg, 0.132 mmol) and 2-(2,5-dichloro-pyrimidin-4-ylamino)-N-methyl-benzenesulfonamide (48.3 mg, 0.145 mmol, 1.1 eq) were dissolved in IPA (1.2 mL). 4.0 M HCl in dioxane (36 μL, 0.145 mmol, 1.1 eq) was added and the reaction was heated at 130° C. in a microwave for 20 minutes. The reaction was then concentrated under reduced pressure and the residue was taken up in CH2Cl2 (10 mL) and washed with sat. NaHCO3 (10 mL). The organic layer was dried (sodium sulfate), filtered, and concentrated under reduced pressure. Purification by preparative HPLC using a gradient of 5-75% acetonitrile/water as the eluting solvent to obtain 2-[5-chloro-2-(10-cyanomethyl-10-aza-tricyclo[6.3.2.0*2,7*]trideca-2,4,6-trien-4-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzenesulfonamide as an orange film (13 mg, 19%). LCMS (m/e) 524 (M+1); 1H-NMR (CDCl3, 400 MHz) δ 9.11 (s, 1H), 8.48 (d, 1H, J=8.3 Hz), 8.07 (s, 1H), 7.95 (dd, 1H, J=1.5 and 8.0 Hz), 7.60-7.53 (m, 1H), 7.35-7.20 (m, 3H), 7.05-6.99 (m, 2H), 4.86 (bs, 1H), 3.55 (s, 2H), 3.10-3.01 (m, 1H), 2.99-2.91 (m, 1H), 2.91-2.83 (m, 2H), 2.64 (s, 3H), 2.58 (d, 2H, J=9.9 Hz), 2.15 (d, 2H, J=8.3 Hz), 1.68 (d, 2H, J=9.4 Hz).

1. concentrationThe reaction was then concentrated under reduced pressure
2. washwashed with sat. NaHCO3 (10 mL)
3. dry with materialThe organic layer was dried (sodium sulfate)
4. filtrationfiltered
5. concentrationconcentrated under reduced pressure
6. customPurification by preparative HPLC