Reaction Steps
To a nitrogen purged flask was added the N-((1R,2R)-2-(3-(4-(hex-5-ynyloxy)phenyl)propylamino)-1,2-diphenylethyl)-4-methylbenzenesulfonamide (116 mg, 0.200 mmol), Cu(OAc)2 (7 mg, 0.04 mmol) and sodium-(L)-ascorbate (16 mg, 0.08 mmol) and degassed solution of 1/1 THF/water (5 cm3). To the stirred solution was then added benzyl azide (32 mg, 0.24 mmol). The reaction became a blue colour when stirred and then became cloudy white. The reaction was stirred at room temperature for 48 hours. After this EtOAc (10 cm3) was added followed by ammonium hydroxide (35%) solution. The EtOAc was separated and aqueous phase extracted with further EtOAc (2×10 cm3). The EtOAc phases were combined and washed with further ammonium hydroxide (35%) solution. The EtOAc phases were dried over Na2SO4, filtered and the solvent removed under reduced pressure to leave the product as a white solid (140 mg, 0.19 mmol, 95%). Purification was not necessary. Mp 123-124° C.; [α]D27−25.2 (c 0.25 in CHCl3) (R,R); (found (ESI): M++H, 714.3481 C43H48N5O3S requires M, 714.3472); υmax 2925, 1510, 1454, 1324, 1241, 1155, 1047, 811, 698 cm−1; δH (400 MHz, CDCl3) 7.38-7.34 (4H, m, CHAr), 7.25-7.21 (3H, m, CHAr), 7.13-7.10 (3H, m, CHAr), 7.04-7.00 (5H, m, CHAr), 6.97-6.88 (6H, m, CHAr), 6.75 (2H, d, J 8.5 Hz, CHAr), 6.30 (1H, br s, NH), 5.46 (2H, s, ArCH2NNN), 4.25 (1H, d, J 7.9 Hz, CHNHSO2), 3.93 (2H, t, J 5.7 Hz, CH2OAr), 3.59 (1H, d, J 7.9 Hz, CHNH), 2.76 (2H, t, J 7.0 Hz, CH2CNNN), 2.49-2.38 (3H, m, CH2Ar and CHHNH), 2.31-2.24 (4H, m, CH3 and CHHNH overlapping), 1.84-1.81 (4H, m, CH2CH2CH2CH2OAr), 1.69-1.61 (2H, m, CH2CH2NH); δC (100 MHz, CDCl3) 157.18 (CAr), 148.42 (CAr), 142.72 (CAr), 139.31 (CAr), 138.40 (CAr), 137.09 (CAr), 133.76 (CAr), 129.21 (2 CHAr), 129.12 (2 CHAr), 129.09 (2 CHAr), 128.64 (CHAr), 128.31 (2 CHAr), 128.01 (2 CHAr), 127.93 (2 CHAr), 127.58 (2 CHAr), 127.45 (2 CHAr), 127.28 (CHAr), 127.11 (2 CHAr), 120.72 (CHAr), 114.37 (2 CHAr), 82.82 (CH), 67.76 (CH), 67.52 (CH2), 65.19 (C), 63.14 (CH), 62.18 (C), 54.01 (CH2), 46.44 (CH2), 32.37 (CH2), 31.70 (CH2), 28.88 (CH2), 25.98 (CH2), 25.46 (CH2), 21.46 (CH3); m/z (ESI) 714.3 (M++1).
