Dimethylformamide → HCID 58860800, compound

Participants

Reaction Conditions

Reaction Steps

n-BuLi (17 mL of a 1.6M solution in hexanes, 27.2 mmol) was added to a stirred solution of (E)-2-(4-bromophenyl)-3-(tetrahydropyran-4-yl)-N-thiazol-2-ylacrylamide (EXAMPLE 12, 4.00 g, 10.2 mmol) in anhydrous THF (100 mL) at −78° C. After 110 min, the mixture was treated with anhydrous DMF (5 mL, 64.6 mmol), before being allowed to warm to 20° C. over 30 min. The reaction was quenched with 1M HCl, then the THF was evaporated off under reduced pressure. The aqueous phase was extracted with CH2Cl2, then the CH2Cl2 extracts were dried (MgSO4), filtered, and concentrated. The residue was stirred with Na2S2O5 solution. The solid produced was collected and triturated with EtOAc. This material was then suspended in EtOAc, then saturated aqueous NaHCO3 was added with stirring. The layers were separated, then the aqueous phase was extracted with EtOAc and CH2Cl2. The combined organic layers were dried, filtered, concentrated, and subjected to column chromatography (CH2Cl2-THF, 93:7), to give EXAMPLE 125 (RTB=1.30 min; m/z (ES+)=371.2 [M+H]+) and EXAMPLE 126 (RTB=1.38 min; m/z (ES+)=343.4 [M+H]+). The EtOAc washings from the bisulfite addition complex were concentrated, then the residue was subjected to flash chromatography (CH2Cl2-THF, 24:1 to 93:7) to give EXAMPLE 124 (RTB=1.39 min; m/z (ES+)=315.3 [M+H]+) and an additional quantity of EXAMPLE 126.

Provenance & Evidence