Benzyl (2,4-difluoro-3-formylphenyl)carbamate → HCID 58316916, compound

Participants

Reaction Conditions

Reaction Steps

In a round bottom flask, 4-chloro-5-iodo-7-(toluene-4-sulfonyl)-7H-pyrrolo[2,3-d]pyrimidine (29, 1.549 g, 3.572 mmol) is combined with 25.0 mL of tetrahydrofuran and the solution is cooled to −50° C. under nitrogen. Isopropylmagnesium chloride (2.76 mL, 2.0 M in tetrahydrofuran, 5.00 mmol) is added slowly and the reaction is allowed to warm to 5° C. over 70 minutes, then cooled to −45° C. In a separate vessel, (2,4-difluoro-3-formyl-phenyl)-carbamic acid benzyl ester (33, 805 mg, 2.76 mmol) in 5 mL of tetrhydrofuran is cooled to −5° C. and o-tolylmagnesium chloride (2.76 mL, 1 M in tetrahydrofuran, 2.76 mmol) is added dropwise slowly, maintaining the temperature at −5° C. for 1 hour. This is then cooled to −30° C. and added to the above 4-chloro-5-iodo-7-(toluene-4-sulfonyl)-7H-pyrrolo[2,3-d]pyrimidine reaction mixture. The resulting reaction mixture is warmed to room temperature over 2-3 hours, then quenched with the addition of 1 M aqueous citric acid and extracted with ethyl acetate. The organic layer is washed with water, brine and dried over magnesium sulfate, then filtered and the filtrate is concentrated under vacuum. The resulting material is purified by silica gel column chromatography eluting with ethyl acetate and hexane. Appropriate fractions are combined and concentrated under vacuum to provide the desired compound (34, 445 mg). MS (ESI) [M+H+]+=598.8.

Provenance & Evidence