Lithium Hexamethyldisilazide → HCID 86617877, compound

Participants

Reaction Steps

To a −78° C. solution of N-(4-acetyl-6-{benzyl[(2-methylcyclopropyl)methyl]amino}pyridin-2-yl)-N-methylpropane-2-sulfonamide (100 mg, 0.23 mmol) from Step B in 1.5 mL dry THF was added lithium bis(trimethylsilyl)amide (244 μL, 0.49 mmol, 2M solution in THF), and the resulting mixture was allowed to stir for 15 min. To this mixture was added a solution of tert-butyl (1R) -1-benzyl-1-methyl-2-oxoethylcarbamate (61 mg, 0.23 mmol, prepared according to preparation of intermediate III up to step C) dissolved in 1 mL dry THF. The solution was allowed to slowly warm to rt and then allowed to stir for an additional 16 h, at which time it was quenched with a saturated solution of ammonium chloride (15 mL) and extracted with ethyl acetate (2×25 mL). The combined organics were dried over sodium sulfate and concentrated. Purification by reverse-phase chromatography afforded tert-butyl (1R,2E)-1-benzyl-4-{2-{benzyl[(2-methylcyclopropyl)methyl]amino}-6-[(isopropylsulfonyl)(methyl)amino]pyridin-4-yl}-1-methyl-4-oxobut-2-enylcarbamate, intermediate n, as an orange oil. LCMS [M+H]=675.3.

Provenance & Evidence