3-Benzyloxybenzyl bromide

Synthesis of Compound 172 Synthesis of Compound 172 Using the procedure reported by K. Thakkar et al., J. Med. Chem., 1993, 36 (20), 2950. [0500] Phosphorus tribromide (1.96 mL, 20.6 mmol) was added to a solution of 3-benzyloxybenzyl alcohol (4.29 g, 20 mmol) in anhydrous dichloromethane (90 mL) at 0° C. The mixture was stirred at 0° C. for 2 h and then at room temperature for 1 h. The reaction was poured onto ice/water (400 mL) and allowed to warm to room temperature. The aqueous solution was extracted with Et2O (5.x.100 mL) and the combined ethereal solution dried (MgSO4). Concentration in vacuo gave a light yellow oil which crystallised on standing to give OBS01018 as colourless needles (4.93 g, 89percent). TLC [SiO2, EtOAc-n-hexane (1:1)] Rf=0.9; m.p. 55-56° C. [Lit. (Petroleum ether): 55° C.]; 1H-NMR (400 MHz, CDCl3) 4.44 (2H, s), 5.05 (2H, s); 6.78 (1H, d, J=2), 6.93 (1H, m), 7.22 (1H, t, J=8), 7.40 (5H, m).3-Hydroxybenzaldehyde (5.00 g, 0.041 mol) was dissolved in anhydrous acetonitrile (130 mL) under argon atmosphere. Cesium carbonate (20.01 g, 0.061 mol) was added and the suspension stirred for 5 min. Benzyl bromide (11.69 mL, 0.102 mol) was then added and the solution heated at reflux for 16 h. The solution was concentrated on rotary evaporator, water was added and the mixture was extracted with EtOAc. The organic phase was washed twice with water, once with brine, dried over MgSOIn an ice cooled solution of 3-benzyloxy-phenylmethanol (2.14 g, 10 mmol) in Et4-[(3-Benzyloxybenzyl)(4-cyanophenyl)amino]-4H-[1, 2, 4]triazole (OBS01019, STX675) To a suspension of NaH (60percent dispersion in oil, 0.22 g, 5.4 mmol) in anhydrous DMF (20 mL) at room temperature was added a solution of 4-[(4-cyanophenyl)amino]-4H-[1, 2, 4]triazole (see LWO02023) (1.0 g, 5.4 mmol) in anhydrous DMF (4 mL) and the mixture stirred under a positive flow of dry nitrogen for 1 h. The orange-yellow suspension was then treated with a solution of OBS01018 (1.57 g, 5.66 mmol) in anhydrous DMF (5 mL) and the mixture was stirred at room temperature overnight. The mixture was transferred to a separating funnel and diluted with EtOAc (100 mL). The organic layer was washed with water (4*100 mL), brine (100 mL), and dried (MgSO4). Concentration in vacuo gave a residue which was recystallised from i-PrOH to give OBS01019 as a white solid (0.58 g, 28percent). TLC [SiO2, EtOAc-n-hexane (1:1)] Rf=0.15 (blue fluorescence at 254 nm); 1H-NMR (400 MHz, CDCl3) 4.85 (2H, s), 5.03 (2H, s); 6.62 (2H, AA'BB'), 6.77 (1H, d, J=7.8), 6.79 (1H, d, J=2.4), 6.96 (1H, dd, J=7.8, 2.4), 7.26 (11H, t, J=7.8), 7.34-7.37 (5H, m), 7.57 (2H, AA'BB'), 8.04 (2H, s); LC-MS: tR=6.81 min, M+H=382 (Waters 2790 Alliance HPLC/ZQ MicroMass spectrometer with PDA detector using APCI, gradient elution: 5:95 MeCN/H2O-95:5 MeCN/H2O over 10 mins then 95:5 MeCN/H2O-5:95 MeCN/H2O using Waters 'Symmetry' C18 (packing: 3.5 mum), 100 mm column); HPLC (Waters 717+Autosampler with PDA detector, using Waters 'Symmetry' C18 (packing: 3.5 mum), 4.6*150 mm column, 90:10 MeOH/H2O) tR=2.27 min (98percent purity).4- [(3-Benzyloxybenzyl)(4-cyanoplzenyl)amino]-4H-[1, 2, 4]triazole;To a stirred suspension of NaH (60percent dispersion in oil, 0.22 g, 5.4 mmol) in anhydrous DMF (5 mL) was added a solution of 4-[(4-cyanophenyl)amino]-4H-[1, 2, 4]triazole (1.0 g, 5.68 mmol) in anhydrous DMF (3 mL) and the mixture stirred at r. t. for 0.5h. A solution of

Molecular Weight:277.16
XLogP3:4.3
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:4
Exact Mass:276.01498
Monoisotopic Mass:276.01498
Topological Polar Surface Area:9.2
Heavy Atom Count:16
Complexity:189
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes