Diisopropylethylamine → methyl (1S)-1-[({(1S,3S,4S)-4-{[(2,6-dimethylphenoxy)acetyl]amino}-3-hydroxy-5-phenyl-1-[4-(2-pyridinyl)benzyl]pentyl}amino)carbonyl]-2,2-dimethylpropylcarbamate

Participants

Reaction Conditions

Reaction Steps

A solution containing the product from Example 2C (0.020 g, 0.038 mmol) in THF (0.4 mL) was treated with 2,6-dimethylphenoxy acetic acid (U.S. Pat. No. 5,914,332, see Example 1H) (0.008 g, 0.044 mmol), DEPBT (0.017 g, 0.057 mmol), and N,N-diisopropylethylamine (0.030 mL, 0.172 mmol), stirred at 25° C. for 16 hours. The mixture was 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 0-80% ethyl acetate/chloroform to give the title compound (0.021 g, 77% yield). 1H NMR (300 MHz, DMSO-d6), δ ppm 0.83 (s, 9 H), 1.52 (m, 2 H), 2.08 (s, 6 H), 2.72 (m, 2 H), 2.80 (m, 2 H), 3.51 (s, 3 H), 3.72 (m, 1 H), 3.85 (d, J=9.19 Hz, 1 H), 4.01 (s, 2 H), 4.22 (m, 2 H), 5.05 (d, J=5.88 Hz, 1 H), 6.71 (d, J=9.93 Hz, 1 H), 6.92(m, 3 H), 7.26 (m, 8 H), 7.45 (d, J=9.56 Hz, 1 H), 7.85 (m, 5 H), 8.62 (d, J=4.78 Hz, 1 H).

Provenance & Evidence