Pyridine → HCID 9900648, compound

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Reaction Steps

To a solution of the compound of Example 16, Step 2 (30 mg, 0.2 mmol) in THF (1.2 ml) was added cyclohexylmagnesium chloride (2 M in ether, 1.0 ml, 2 mmol) at −44° C. under argon, the reaction was slowly warmed to room temperature, and stirred to for 10 min. Saturated NH4Cl was added, the resulting mixture was extracted several times with EtOAc, the combined organic layer dried, filtered through a silica gel pad, and concentrated to give yellow oil. The oil was dissolved in CH2Cl2 (2 ml), then pyridine (80 μl, 0.9 mmol) and ethyl chloroformate (50 μl, 0.5 mmol) were added, the mixture was stirred at room temperature for 30 min, stirred for another 10 min after which H2O (25 μl) and EtOAc were added, and the mixture dried over Na2SO4, filtered through a silica gel pad, and concentrated to give yellow oil. The oil was dissolved in CH3CN (2 ml), H2O (0.3 ml) and TFA (0.2 ml) were added, and the mixture stirred at room temperature for 2 h. Saturated NaHCO3 solution and EtOAc were added, the aqueous layer was separated and extracted with EtOAc, and the combined organic layer was dried over Na2SO4, concentrated and chromatographed on silica gel to give 35 mg of desired product as yellow foam (60%). MS (M+H)+=392. HPLC RT=3.60 min (YMC S5 ODS column 4.6×50 mm, 10-90% aqueous methanol over 4 minutes containing 0.2% phosphoric acid, 4 ml/min, monitoring at 220 nm)

Provenance & Evidence