Reaction Steps
A solution of toluene-4-sulfonic acid trans-3-[4-amino-5-(2-phenylquinolin-7-yl)pyrrolo[2,3-d]pyrimidin-7-yl]-cyclobutylmethyl ester and azetidine (0.30 mL, 254 mg, 4.5 mmol) in THF (4 mL) was heated in a sealed tube to 50° C. overnight. More azetidine (0.30 mL, 254 mg, 4.5 mmol) was added, and heating was continued overnight. THF was evaporated, water and saturated NaHCO3 solution were added, the mixture was extracted with CH2Cl2 (5×20 mL), and the combined CH2Cl2 extracts were washed with water and brine and dried over MgSO4. The crude material was purified by chromatography on silica gel [Jones Flashmaster, 5 g/25 mL cartridge, eluting with CH2Cl2 (1-9)→5% MeOH in CH2Cl2 (10-31)→6.6% MeOH in CH2Cl2 (32-55)→6.6% MeOH in CH2Cl2+NH3 (0.05 M) (56-86)], yielding the title compound as a highly viscous yellow oil. This oil was dissolved in CDCl3 (0.7 mL), tBuOMe was added, and the off-white precipitate was filtered off and dried in vacuo yielding the desired product. 1H NMR (CDCl3, 400 MHz) δ 2.15 (quint, J=7.2 Hz, 2H), 2.33-2.54 (m, 4H), 2.57-2.70 (m, 3H), 2.73 (d, J=7.4 Hz, 2H), 3.33 (t, J=7.2 Hz, 4H), 5.26 (brs, 2H), 5.44 (quint, J=8.1 Hz, 1H), 7.37 (s, 1H), 7.46-7.52 (m, 1H), 7.52-7.58 (m, 2H), 7.70 (dd, J=1.7, 8.3 Hz, 1H), 7.91 (d, J=8.5 Hz, 1H), 7.93 (d, J=7.2 Hz, 1H), 8.17-8.22 (m, 2H), 8.26 (d, J=8.6 Hz, 1H), 8.28-8.31 (m, 1H), 8.35 (s, 1H). 13C NMR (CDCl3, 100.6 MHz, DEPT135) δ 17.73 (−), 27.06 (+), 33.60 (2C, −), 46.72 (+), 55.51 (2C, −), 63.99 (−), 101.05 (Cquart), 116.12 (Cquart), 118.85 (+), 120.57 (+), 125.86 (Cquart), 127.29 (+), 127.45 (2C, +), 128.18 (+), 128.34 (+), 128.76 (2C, +), 129.41 (+), 136.31 (Cquart), 136.46 (+), 139.30 (Cquart), 148.38 (Cquart), 150.73 (Cquart), 151.83 (+), 157.07 (Cquart), 157.95 (Cquart). MS (ES+): m/z 461.2 (11) [MH+], 338.2 (14) [MH+−C4H5CH2azetidine]. HPLC: tR=2.0 min (OpenLynx, polar—5 min).
