Cyclopropanecarbonyl chloride → HCID 53242133, compound

Participants

Reaction Conditions

Reaction Steps

To a mixture of (S)-7-amino-2-(1-(3-ethoxy-4-hydroxyphenyl)-2-(methylsulfonyl)ethyl)isoindolin-1-one (5.86 g, 15.0 mol) in THF (60 mL) was added cyclopropanecarbonyl chloride (1.5 mL, 16.1 mmol). The mixture was heated to 60° C. for 1 hour then cooled to room temperature. The solvent was removed and the crude residue purified using column chromatography (MeOH/CH2Cl2; 0-5% over 60 minutes) to give 4.7 g of crude, 68% yield. Further purification was then carried out by prep-HPLC to give (S)—N-(2-(1-(3-ethoxy-4-hydroxyphenyl)-2-(methylsulfonyl)ethyl)-3-oxoisoindolin-4-yl)cyclopropanecarboxamide as a white solid (1.38 g, 20% yield). HPLC: HPLC: Hypersil DBS C8 column, 250×4.6 mm, 5 μm; 99/1 to 85/15 over 15 min Gradient CH3CN/10 mM aq. KH2PO4, 1.0 mL/min, 35° C., run time 20 minutes: tR 12.45 minutes. 1H-NMR (DMSO-d6): 10.51 (1H, s), 9.07 (1H, s), 8.22-8.25 (1H, d), 7.47-7.53 (1H, t), 7.18-7.20 (1H, d), 7.01 (1H, d), 6.78-6.86 (2H, m), 5.82-5.87 (1H, m), 4.61-4.67 (1H, d), 3.91-4.33 (5H, m), 3.02 (3H, s), 1.76-1.82 (1H, m), 1.31-1.36 (3H, t), 0.82-0.96 (4H, m); LC-MS ES+ (M+1) 459.

Provenance & Evidence