Cyclopropanecarbonyl chloride → HCID 67254365, compound

Participants

Reaction Conditions

Reaction Steps

To a mixture of (S)-7-amino-2-(1-(3-hydroxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl)isoindolin-1-one (5.86 g, 15.6 mmol) 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-hydroxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl)-3-oxoisoindolin-4-yl)cyclopropanecarboxamide as a white solid (0.3 g, 4.3% yield). HPLC: HPLC: Hypersil DBS C8 column, 250×4.6 mm, 5 μm; 99/1 to 85/15 over 15 minutes Gradient CH3CN/10 mM aq. KH2PO4, 1.0 mL/min, 35° C., run time 20 minutes: tR 11.84 minutes. 1H-NMR (DMSO-d6): 10.50 (1H, s), 9.11 (1H, s), 8.22-825 (1H, d), 7.48-7.53 (1H, t), 7.18-7.2 (1H, d), 6.84-6.95 (3H, m), 5.80-5.85 (1H, m), 4.60-6.66 (1H, d), 3.90-4.30 (3H, m), 3.75 (3H, s), 3.04 (3H, s), 1.79-1.83 (1H, m), 0.88-0.90 (4H, m); LC-MS ES+ (M+1) 445.

Provenance & Evidence