1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) → HCID 71711978, compound

Participants

Reaction Steps

To a 10-20 ml microwave vial charged with N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (INTERMEDIATE M) (0.05 g, 0.120 mmol), 3-bromo-2-methoxy-6-(trifluoromethyl)pyridine (Anichem) (0.046 g, 0.180 mmol), sodium t-butoxide (0.029 ml, 0.240 mmol), xantphos (0.014 g, 0.024 mmol), and Pd2(dba)3 (10.97 mg, 0.012 mmol) was added toluene (1.198 ml). The mixture was purged with argon and the vessel was sealed and irradiated at 130° C. for 30 mins. LC-MS indicated complete conversion to desired product (PMB protected, m/z=593). To the mixture was added TFA (200 μl) and the resulting mixture stirred at room temperature for 2 hrs. The mixture was filtered through celite and the filtrate dried under reduced pressure. The crude material was purified with a 25 g HP spherical silica column (15 μm, Interchim) ramping EtOAc in heptane (0-50%, then isocratic at 50%, 10% DCM isocratic throughout) providing product as a film which was lyophilized yielding an off-white solid. The material was further purified with preparative RP-HPLC ramping ACN in H2O (10-90%, 0.1% TFA) affording 4-(2-methoxy-6-(trifluoromethyl)pyridin-3-yl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (10 mg, 18%). 1H NMR (400 MHz, DMSO-d6) δ ppm 3.67-3.72 (m, 2 H) 3.92 (s, 3 H) 4.29-4.33 (m, 2 H) 6.44 (d, J=8.51 Hz, 1 H) 6.79 (d, J=4.60 Hz, 1 H) 7.13 (dd, J=8.51, 2.15 Hz, 1 H) 7.16 (d, J=2.05 Hz, 1 H) 7.22 (d, J=4.60 Hz, 1 H) 7.56 (d, J=7.92 Hz, 1 H) 7.90-7.97 (m, 1 H). m/z (ESI) 473.2 (M+H)+.

Provenance & Evidence