Reaction SMILES: O[C:2]([CH2:4][CH2:5][CH2:6][CH2:7][C@H:8]1[C@@H:16]2[C@@H:11]([NH:12][C:13]([NH:15]2)=[O:14])[CH2:10][S:9]1)=[O:3].Cl.[CH3:18][O:19][C:20](=[O:28])[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][NH:26][CH3:27].C(N(CC)CC)C.P(=O)([O-])[O-].P(=O)([O-])[O-].P(=O)([O-])[O-].P(=O)([O-])[O-].P(=O)([O-])[O-].P(=O)([O-])[O-].N1C2C=CC=C(O[P+](N(C)C)(N(C)C)N(C)C)C=2N=N1.N1C2C=CC=C(O[P+](N(C)C)(N(C)C)N(C)C)C=2N=N1.N1C2C=CC=C(O[P+](N(C)C)(N(C)C)N(C)C)C=2N=N1.N1C2C=CC=C(O[P+](N(C)C)(N(C)C)N(C)C)C=2N=N1.N1C2C=CC=C(O[P+](N(C)C)(N(C)C)N(C)C)C=2N=N1.N1C2C=CC=C(O[P+](N(C)C)(N(C)C)N(C)C)C=2N=N1.N1C2C=CC=C(O[P+](N(C)C)(N(C)C)N(C)C)C=2N=N1.N1C2C=CC=C(O[P+](N(C)C)(N(C)C)N(C)C)C=2N=N1.N1C2C=CC=C(O[P+](N(C)C)(N(C)C)N(C)C)C=2N=N1.N1C2C=CC=C(O[P+](N(C)C)(N(C)C)N(C)C)C=2N=N1.N1C2C=CC=C(O[P+](N(C)C)(N(C)C)N(C)C)C=2N=N1.N1C2C=CC=C(O[P+](N(C)C)(N(C)C)N(C)C)C=2N=N1>CN(C)C=O>[CH3:27][N:26]([CH2:25][CH2:24][CH2:23][CH2:22][CH2:21][C:20]([O:19][CH3:18])=[O:28])[C:2](=[O:3])[CH2:4][CH2:5][CH2:6][CH2:7][C@H:8]1[C@@H:16]2[C@@H:11]([NH:12][C:13]([NH:15]2)=[O:14])[CH2:10][S:9]1
Reactant: CNCCCCCC(=O)OC
Reactant: O=C(O)CCCC[C@@H]1SC[C@@H]2NC(=O)N[C@@H]21
Agent: CN(C)[P+](Oc1cccc2[nH]nnc12)(N(C)C)N(C)C
Agent: Cl
Agent: O=[PH]([O-])[O-]
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: COC(=O)CCCCCN(C)C(=O)CCCC[C@@H]1SC[C@@H]2NC(=O)N[C@@H]21
Temperature: 25 °C
Reaction time: 13 h

Procedure:
To a 500 mL round bottom flask, charged with 9.00 g (36.8 mmol) of biotin (Sigma Chemical Company), 7.93 g (40.5 mmol, 1.1 equiv.) of amine hydrochloride 12, and 200 mL of anhydrous dimethylformamide was added 17 mL of triethylamine (120 mmol) followed by 17.1 g (38.7 mmol, 1.05 equiv.) of benzotriazolyloxytris(dimethylamino)phosphonium hexaphosphonate (BOP, commercially available from Aldrich Chemical Company and Chem-Impex International, Wood Dale, Ill.) coupling agent. The reaction was stirred at room temperature for 13 h and then concentrated. The residue was diluted with 100 mL of 2-propanol and 300 mL of methylene chloride and the resulting mixture was washed with 2×150 mL aliquots of 1N aqueous HCl and then with 150 mL of de-ionized water. The organic phase was dried with anhydrous magnesium sulfate and vacuum filtered. The solids were rinsed with 100 mL of 25% 2-propanol/methylene chloride. The combined filtrates were concentrated. The residue was chromatographed on 9×22 cm of silica gel, eluting with 20% methanol/ethyl acetate. The fractions containing product (13) were combined and concentrated via rotary evaporation. The residue was chromatographed on 7×18 cm of RP-18 silica gel, eluting with 800 mL of 50:50 methanol/water, 1 liter of 55:45 methanol/water and 2 liters of 60:40 methanol/water. The fractions containing product (13) were combined and concentrated, first via rotary evaporation and finally under full vacuum pump pressure (<0.5 mm Hg) to afford 11.58 of the product (13) as a near colorless oil: 1H NMR (d6-DMSO) d 6.42 (1H, s), 6.33 (1H, s), 4.29 (1H, m), 4.12 (1H, m), 3.57 (3H, s), 3.22 (2H, t), 3.09 (1H, m), 2.91 and 2.77 (3H, 2 s), 2.81 (1H, dd), 2.57 (1H, d), 2.34-2.19 (4H, m) and 1.70-1.10 (12H, m) ppm; 1H NMR (CD3pk OD) d 4.48 (1H, dd), 4.29 (1H, dd), 3.63 and 3.62 (3H, 2 s), 3.34 (2H, t), 3.20 (1H, m), 3.02 and 2.88 (3H, 2 s), 2.91 (1H, dd), 2.68 (1H, d), 2.43-2.27 (4H, m) and 1.80-1.20 (12H, m) ppm; Thin Layer Chromatography (Visualization with p-aminocinnimaldehyde spray); Silica Gel, Rf=0.31 ({fraction (80/20)} ethyl acetate/methanol); RP-18 Silica Gel, Rf=0.29 ({fraction (60/40)} methanol/water).