Phosgene → [1-(4-fluorobenzyl)cyclobutyl]methyl(1S)-5-{[(dimethylamino)sulfonyl]amino}-1-{1-hydroxy-2-oxo-2-[(3-pyridinylmethyl)amino]ethyl}pentylcarbamate

Participants

Reaction Steps

To 110 mg (0.57 mmol) of [1-(4-fluorobenzyl)cyclobutyl]methanol in 2 mL of tetrahydrofuran was added 0.59 mL (1.1 mmol) of 1.93 M phosgene in toluene and the reaction stirred at room temperature overnight. The mixture was concentrated under reduced pressure and added to a solution of 250 mg (0.57 mmol) of (3S)-3-amino-7-{[(dimethylamino)sulfonyl]amino}-2-hydroxy-N-(3-pyridinylmethyl)heptanamide dihydrochloride and 0.28 mL of triethylamine in 4 mL of tetrahydrofuran. The mixture was filtered through a frit and the wash concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with 7:3 acetone:hexanes to leave 200 mg (59%) of [1-(4-fluorobenzyl)cyclobutyl]methyl(1S)-5-{[(dimethylamino)sulfonyl]amino}-1-{1-hydroxy-2-oxo-2-[(3-pyridinylmethyl)amino]ethyl}pentylcarbamate. 1H NMR (300 MHz, DMSO-d6) δ 8.38-8.55 (m, 2H), 7.65 (m, 1H), 6.7.00-7.40 (m, 7H), 6.55 (d, J=9 Hz, 1H), (5.83 (d, J=6 Hz) and 5.72 (J=6 Hz), 1H), 4.31 (m, 2H), 4.00 (m, 1H), 3.71-3.88 (m, 2H), 3.42 under water peak (m, 2H), 2.74-2.90 (m, 3H), 2.66 (s, 6H), 1.70-1.95 (m, 6H), 1.25-1.59 (m, 6H). ES-LCMS m/z 594 (M+H).

Provenance & Evidence