Hydrochloric Acid → (3S,5S,8S)-3-((1S)-1-{[(2S)-2-(3-benzyl-2-oxoimidazolidin-1-yl)-3,3-dimethylbutanoyl]amino}-2-phenylethyl)-8-tert-butyl-7,10-dioxo-5-(4-pyridin-2-ylbenzyl)-2,11-dioxa-6,9-diazadodec-1-yl (dimethylamino)acetate

Participants

Reaction Steps

To a solution of the product from Example 195A (0.045 g, 0.052 mmol) in 1,2-dichloromethane (1.5 mL) were added molecular sieves (4 Å, 0.24 g), N,N-dimethylglycine hydrochloride (0.075 g, 0.537 mmol), followed by N-iodosuccinimide (0.013 g, 0.058 mmol), and the mixture was stirred at room temperature for 2 hours. The reaction was filtered through celite. The filtrate was diluted with ethyl acetate and was washed with a mixture of dilute NaHCO3 and Na2S2O3, dried over MgSO4, filtered and evaporated. The residue was dissolved in ether and 2 equivalents of 4 N HCl in dioxane were added. The crude product was purified by chromatography on silica gel eluting with a gradient starting with dichloromethane and ending with methanol to give the title compound as the bis hydrochloride salt (0.037 g, 77% yield). 1H NMR (300 MHz, DMSO-d6), δ ppm 0.87 (s, 9 H), 0.88 (s, 9 H), 1.60-1.73 (m, 2 H), 2.22 (s, 6 H), 2.29 (q, J=9.6 Hz, 1 H), 2.54-2.84 (m, 6 H), 2.93 (q, J=8.8 Hz, 1 H), 3.08-3.24 (m, 4 H), 3.53 (s, 3 H), 3.72-3.76 (m, 1 H), 3.87 (d, J=9.6 Hz, 1 H), 4.11-4.35 (m, 5 H), 5.26 (d, J=6.6 Hz, 1 H), 5.37 (d, J=6.6 Hz, 1 H), 6.78 (d, J=9.6 Hz, 1 H), 6.94-7.15 (m, 5 H), 7.22-7.40 (m, 8 H), 7.82-7.95 (m, 6 H), 8.63 (m, 1 H).

Provenance & Evidence