1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) → HCID 89762106, compound

Participants

Reaction Steps

A microwave vial containing a suspension of 4-(2-bromophenoxy)pyridine (0.180 g, 0.719 mmol), N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (Intermediate M; 0.2 g, 0.479 mmol), sodium t-butoxide (0.117 ml, 0.958 mmol), Xantphos (0.111 g, 0.192 mmol) and tris(dibenzylideneacetone)dipalladium (0) (0.088 g, 0.096 mmol) in toluene (4.79 ml) was purged with nitrogen and was microwave irradiated at 100° C. for 45 min. Reaction mixture was diluted with EtOAc (100 mL) and washed with water (2×50 mL). The organic layer was dried over anhydrous sodium sulfate, concentrated and purified by preperative LC/MS-2 System Column: XBridge 19×100 mm 12230326114 03 Mobile phase: 0.1% NH4OH in water/acetonitrile Flow rate: 40 ml/min Inj: 2200 uL. Gradient: 10 min5-50% shallow; 10 min10-60% shallow to obtain N-(4-methoxybenzyl)-4-(2-(pyridin-4-yloxy)phenyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (0.108 g, 0.184 mmol, 38.4% yield) as yellow solid. The material was then dissolved in DCM (1 mL) and TFA was added (1 ml). The reaction mixture was concentrated and purified by MPLC (Biotage Isolera One; PuriFlash HP, 15p., 80 g), eluting with DCM:MeOH (90:10) to obtain 4-(2-(pyridin-4-yloxy)phenyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (0.03 g, 0.064 mmol, 13.42% yield) as an off white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.57 (br. s., 1 H) 8.30-8.34 (m, 2 H) 7.50-7.54 (m, 1 H) 7.41-7.45 (m, 2 H) 7.33-7.38 (m, 1 H) 7.23 (d, J=4.60 Hz, 1 H) 7.13 (dd, J=8.51, 2.15 Hz, 1 H) 7.02 (d, J=2.15 Hz, 1 H) 6.79 (d, J=4.60 Hz, 1 H) 6.64-6.68 (m, 2 H) 6.43 (d, J=8.51 Hz, 1 H) 3.56 (br. s., 2 H) 3.29 (br. s., 1H); MS (ESI, positive ion) m/z; 467.1 (M+1)

Provenance & Evidence