1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) → HCID 89761842, compound

Participants

Reaction Steps

A microwave vial containing a suspension of 2-(2-bromophenoxy)-2-methylpropanenitrile (0.173 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 (9.58 ml) was purged with nitrogen and was microwave irradiated at 110° C. for 30 min. Reaction mixture was diluted with EtOAc (50 mL) and washed with saturated NaCl solution. Organic layer was 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 4-(2-((2-cyanopropan-2-yl)oxy)phenyl)-N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (44 mg, 0.076 mmol, 16% yield). To the material was then added DCM (1 mL) and TFA (4 drops) and stirred at ambient temperature for 2 h The reaction mixture was 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 4-(2-((2-cyanopropan-2-yl)oxy)phenyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (3.8 mg, 0.008 mmol, 1.6% yield). 1H NMR (500 MHz, DMSO-d6) δ ppm 7.43 (dd, J=8.12, 1.28 Hz, 1 H) 7.39 (dd, J=7.85, 1.55 Hz, 1 H) 7.31-7.37 (m, 1 H) 7.21-7.27 (m, 1 H) 7.11-7.14 (m, 2 H) 7.08 (dd, J=8.55, 2.14 Hz, 1 H) 6.66 (d, J=4.38 Hz, 1 H) 6.34 (d, J=8.44 Hz, 1 H) 5.75 (s, 1 H) 4.26-4.32 (m, 2 H) 3.60-3.65 (m, 2 H) 1.55 (br. s., 6 H); MS (ESI, positive ion) m/z; 457.0 (M+1)

Provenance & Evidence