Cyclopropylamine → HCID 86707740, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-chloroethanol (0.10 mL, 1.3 mmol) in DCM (1 mL) at rt was added a solution of sulfurisocyanatidic chloride (180 mg, 1.3 mmol) in DCM (1 mL) and the reaction mixture was stirred for 6 h. The resulting mixture was added to a solution of Compound 181a (300 mg, 0.65 mmol, prepared as described in Example 45) and TEA (0.45 mL, 3.2 mmol) in DCM (4 mL) and the mixture stirred for 30 min then heated at 35° C. for 16 h. The reaction mixture was concentrated under reduced pressure and the residue was purified by silica gel chromatography eluting with 0-100% hexane/EtOAc to afford (S)-benzyl 2-(2-oxooxazolidine-3-sulfonamido)-3-(5-((6-phenylbenzo[d]thiazol-2-yl)methyl)-1,3,4-oxadiazol-2-yl)propanoate (230 mg, 57% yield) as a yellow foam. LCMS=1.2 min using analytical method (B), 620.2 (M+H). A portion of (S)-benzyl 2-(2-oxooxazolidine-3-sulfonamido)-3-(5-((6-phenylbenzo[d]thiazol-2-yl)methyl)-1,3,4-oxadiazol-2-yl)propanoate (93 mg, 0.15 mmol) was dissolved in ACN (3 mL) then TEA (0.031 mL, 0.23 mmol) was added followed by cyclopropanamine (0.053 mL, 0.75 mmol) and the reaction mixture heated at 70° C. for 16 h. The reaction mixture was allowed to cool to rt then concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with 0-100% hexane/EtOAc to give Compound 181b (41 mg, 46% yield) as a yellow solid. 1H NMR (400 MHz, CDCl3) δ 8.13-7.97 (m, 2H), 7.72 (dd, J=8.5, 1.9 Hz, 1H), 7.67-7.59 (m, 2H), 7.51-7.44 (m, 2H), 7.42-7.38 (m, 1H), 7.34-7.31 (m, 3H), 7.30-7.27 (m, 2H), 5.53 (d, J=8.1 Hz, 1H), 5.23 (s, 1H), 5.18 (s, 2H), 4.68 (d, J=4.4 Hz, 2H), 3.43 (dd, J=5.7, 1.8 Hz, 2H), 2.51-2.35 (m, 1H), 0.65-0.43 (m, 4H). LCMS=1.2 min using analytical method (B), 590.2 (M+H)±.

Provenance & Evidence