Dichloromethane → HCID 70913338, compound

Participants

Reaction Conditions

Reaction Steps

To a dry flask was added zinc dust (40 mg, 0.61 mmol) followed by anhydrous DMA (2 ml) and the vessel was flushed with nitrogen whilst stirring vigorously and heating to 65° C. TMS-Cl (9 μl, 0.07 mmol) and 1,2-dibromoethane (6 μl, 0.07 mmol) were added and the reaction was stirred at 65° C. for 30 mins, followed by the dropwise addition of N-Boc-3-iodoazetidine (133 mg, 0.47 mmol) as a solution in anhydrous DMA (1 ml). The reaction was then cooled to room temperature and methyl 5-bromo-3-[ethyl(oxan-4-yl)amino]-2-methylbenzoate (100 mg, 0.28 mmol) was added as a solution in anhydrous DMA (2 ml). The resulting solution was degassed with nitrogen for 5 mins after which Pd(dppf)Cl2.DCM (7 mg, 0.01 mmol) and copper (I) iodide (3 mg, 0.02 mmol) were added as solids. The reaction was heated to 80° C. for 16 h and then cooled to room temperature followed by the addition of saturated NH4Cl solution (50 ml). The aqueous phase was extracted with EtOAc (3×100 ml), and then the combined organic phases were washed with brine (2×50 ml), dried with Na2SO4, filtered and evaporated. The residue was purified over a 5 g Isolute column using 10-30% EtOAc in heptane as the eluent to afford the title compound as a colourless oil (77 mg, 62%). LC-MS 98%, 2.19 min (3.5 minute LC-MS method), m/z=433.2, 1H NMR (500 MHz, CDCl3) δ 7.49 (d, J=1.6 Hz, 1H), 7.16 (d, J=1.6 Hz, 1H), 4.31 (t, J=8.7 Hz, 2H), 3.94 (dd, J=14.4, 5.5 Hz, 4H), 3.89 (s, 3H), 3.77-3.64 (m, 1H), 3.31 (td, J=11.4, 2.7 Hz, 2H), 3.06 (q, J=7.0 Hz, 2H), 2.99-2.87 (m, 1H), 2.46 (s, 3H), 1.65 (ddd, J=11.1, 8.6, 6.0 Hz, 4H), 1.46 (s, 9H), 0.85 (dd, J=13.1, 6.1 Hz, 3H).

Provenance & Evidence