Reaction Steps
Compound 17 (0.400 g, 1.66 mmol) was placed in ethanol (10 ml) and stirred in an ice-water bath while sodium borohydride (0.063 g, 1.66 mmol) was added. The reaction was brought to room temperature and stirred for 2 hours. The reaction was quenched with water (2 ml), diluted with a saturated NH4Cl solution, and extracted with ethyl acetate. The solution was concentrated in vacuo to yield 18 as a pale orange solid (0.390 g, 99% yield). The product was used in the next step without further purification. Methyl 3′-(hydroxymethyl)bi-phenyl-4-carboxylate 18 (0.210 g, 0.867 mmol) was dissolved in dichloromethane (4 ml) and placed under argon in an ice-water bath. To this solution was added dropwise 0.870 ml of 1.0 M phosphorous tribromide in dichloromethane. The reaction was stirred at room temperature for 2.5 hours and then quenched with 1:1 saturated NaHCO3:water followed by extraction with diethyl ether. The organic layer was dried over Na2SO4 and concentrated in vacuo to yield 19 as a white solid (0.277 g, quant. yield). The product was used for the next reaction without further purification. Methyl 3′-(bromomethyl)biphenyl-4-carboxylate 19 (0.278 g, 0.876 mmol) and sodium azide (0.113 g, 1.73 mmol) were heated to 70° C. in DMF (4 ml) overnight with vigorous stiffing. After 12 hours, the reaction was quenched with water (10 ml) and the product extracted with ethyl acetate (3×10 ml). The organic layers were washed with brine (15 ml), dried over Na2SO4, and concentrated in vacuo to yield 20 as a yellow oil. The product was purified by column chromatography (6:1 Hexane:ethyl acetate) to afford 3′-(azidomethyl)biphenyl-4-carboxylate as a pale orange solid (0.225 g, 92%). 1H NMR (400 MHz, CDCl3) δ 3.94 (s, 3H), 4.42 (s, 2H), 7.34 (d, J=7.6 Hz, 1H), 7.48 (t, J=7.6 Hz, 1H), 7.55-7.60 (m, 2H), 7.66 (d, J=8.4 Hz, 2H), 8.11 (d, J=8.4 Hz, 2H). 3′-(azidomethyl)-biphenyl-4-carboxylate 20 (0.150 g, 0.561 mmol) was heated to reflux in EtOH (4 ml, 80° C.) in the presence of hydrazine monohydrate (0.96 ml of a 20.63 M solution), and the solution was left to stir overnight (12 hours). The reaction was then concentrated in vacuo to remove excess ethanol. Water (10 ml) was added, and the product extracted with ethyl acetate (5×10 ml), dried over Na2SO4, and concentrated in vacuo to yield 5 as a pale yellow solid. The product was isolated by crystallization in 2:1 ethanol:ethyl acetate (0.127 g, 85%). 1H NMR (400 MHz, (CD3)2SO) δ 4.51 (s, 2H), 7.39 (d, J=7.2, 1H), 7.50 (t, J=7.6, 1H), 7.68-7.75 (m, 4H), 7.91 (d, J=8.0 Hz, 2H) 13C NMR (100 MHz, (CD3)2SO) δ 54.0, 127.0, 127.4, 128.1, 128.5, 130.0, 132.8, 136.9, 140.0, 142.6, 165.9; MS (ESI) calculated for C14H13N5O [M+H]+: m/z 268.3. found [M+H]+: 268.2
