Dimethylformamide → HCID 24803254, compound

Participants

Reaction Conditions

Reaction Steps

Dissolve 5-(4-chloro-phenyl)-3-methyl-thiophene-2-carboxylic acid [3-methoxy-4-((R)-3-triisopropylsilanyloxy-pyrrolidin-1-yl)-phenyl]-amide (0.573 g, 0.958 mmol) in THF (10 mL). Cool the mixture to −78° C. under argon. Add t-BuLi (1.2 mL, 2.11 mmol) dropwise and stir at −78° C. for 20 min. Add DMF (1.5 mL) and stir at −78° C. for 10 min, then warm gradually to 0° C. Quench the mixture with saturated NH4Cl (10 mL) then dilute with EtOAc (100 mL) and wash with water (2×30 mL). Dry the solution with Na2SO4, filter, and concentrate. Suspend the resulting crude material in toluene (40 mL) and treat with p-toluenesulfonic acid-H2O (0.45 g, 2.37 mmol). Reflux the mixture using a Dean-Stark trap. Dilute the mixture with EtOAc (150 mL) and wash with saturated NaHCO3 (2×50 mL). Dry the solution with Na2SO4, filter, and concentrate. Purify the crude material by chromatography, eluting with 100% EtOAc to give 0.144 g (33%) of 2-(4-chloro-phenyl)-6-[4-((R)-3-hydroxy-pyrrolidin-1-yl)-3-methoxy-phenyl]-6H-thieno[2,3-c]pyridin-7-one.

Provenance & Evidence