Triethylamine → 1-(benzo[d][1,3]dioxol-5-yl)-N-(5-((S)-(2-chloro-4-fluorophenyl)((R)-1,1-dimethylethylsulfinamido)methyl) thiazol-2-yl)cyclopropanecarboxamide

Participants

Reaction Conditions

Reaction Steps

To a solution of 1-(benzo[d][1,3]dioxol-5-yl)cyclopropanecarboxylic acid (618 mg, 3.0 mmol) in anhydrous CH2Cl2 (6 mL) was slowly added (COCl)2 (0.3 mL, 3.4 mmol) at −10° C. followed by DMF (3 drops). The reaction mixture was stirred at −10° C. for 0.5 h. The excess (COCl)2 was removed under vacuum. The acid chloride (10.5 mmol) was then dissolved in anhydrous CH2Cl2 (3 mL) and was slowly added to a solution of (R)—N—((S)-(2-aminothiazol-5-yl)(2-chloro-4-fluorophenyl)methyl)-2-methylpropane-2-sulfinamide (648 mg, 1.8 mmol) and Et3N (1.8 mL, 6 mmol) in anhydrous CH2Cl2 (3 mL). The reaction mixture was stirred at room temperature for 1 h, diluted with CH2Cl2 and washed with 1 N HCl, NaHCO3 and brine. The organic layer was separated from the aqueous layer and dried over MgSO4 and concentrated. The crude product was purified by column chromatography (40-60% EtOAc/Hexane) to provide 1-(benzo[d][1,3]dioxol-5-yl)-N-(5-((S)-(2-chloro-4-fluorophenyl)((R)-1,1-dimethylethylsulfinamido)methyl)thiazol-2-yl)cyclopropanecarboxamide as a colorless solid (680 mg, 69%). 1H-NMR (400 MHz, CDCl3) δ 8.60 (s, 1H), 7.60 (dd, J=8.7, 5.9 Hz, 1H), 7.28 (d, J=2.0 Hz, 1H), 7.13 (dd, J=8.3, 2.6 Hz, 1H), 7.05 (td, J=8.2, 2.6 Hz, 1H), 6.90 (td, J=8.3, 1.7 Hz, 2H), 6.83 (d, J=7.9 Hz, 1H), 6.18 (d, J=4.3 Hz, 1H), 6.04 (s, 2H), 3.90 (d, J=4.3 Hz, 1H), 1.73 (td, J=5.4, 2.0 Hz, 2H), 1.28 (t, J=7.1 Hz, 2H), 1.29 (s, 9H). HPLC ret. time 3.65 min, 10-99% CH3CN, 5 min run; ESI-MS 550.5 m/z (MH+).

Provenance & Evidence