Diisopropylethylamine → methyl(1S)-1-{[((1s,2s,4s)-1-benzyl-2-hydroxy-4-{[(2s)-3-methyl-2-(2-oxo-3-{[2-(3-pyridinyl)-1,3-thiazol-4-yl]methyl}-1-imidazolidinyl)pentanoyl]amino}-5-phenylpentyl)amino]carbonyl}-2,2-dimethylpropylcarbamate

Participants

Reaction Conditions

Reaction Steps

A solution containing the product from Example 8B (0.275 g, 0.56 mmol) in THF (6 mL) was treated with the product from Example 3L (0.227 g, 0.61 mmol), DEPBT (0.275 g, 0.92 mmol), and N,N-diisopropylethylamine (0.55 mL, 3.16 mmol), stirred at 25° C. for 64 hours, and partitioned between ethyl acetate and 10% Na2CO3 solution. The organic phase was washed with additional 10% Na2CO3 solution and brine, dried over MgSO4, filtered and concentrated. The residue was chromatographed on silica gel eluting with 0-100% ethyl acetate/dichloromethane, followed by elution with 5% methanol in ethyl acetate to give the title compound (0.378 g, 77% yield). 1H NMR (300 MHz, DMSO-d6), δ ppm 0.67 (d, J=6.62 Hz, 3 H), 0.80 (m, 14 H), 0.94 (m, 1 H), 1.29 (m, 1 H), 1.49 (m, 2 H), 1.78 (m, 1 H), 2.42 (m, 1 H), 2.68 (m, 3 H), 2.86 (m, 1 H), 3.13 (m, 4 H), 3.58 (m, 4 H), 3.89 (m, 2 H), 4.12 (m, 2 H), 4.47 (s, 2 H), 4.79 (d, J=5.52 Hz, 1 H), 6.80 (d, J=9.19 Hz, 1 H), 7.07 (m, 7 H), 7.52 (m, 2 H), 7.57 (s, 1 H), 7.82 (d, J=8.82 Hz, 1 H), 8.29 (m, 1 H), 8.66 (dd, J=4.78, 1.84 Hz, 1 H), 9.13 (d, J=1.47 Hz, 1 H).

Provenance & Evidence