4-Methanesulfonylmorpholine → 3-ethyl-1-(morpholinosulfonylmethyl)-4-(6-((2-(trimethylsilyl)ethoxy)methyl)-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentanol

Participants

Reaction Conditions

Reaction Steps

To a solution of 4-(methylsulfonyl)morpholine (0.217 g, 1.314 mmol, Preparation #41) in THF (4 mL) at about 0° C. was added n-BuLi (2.5 M in hexanes, 0.53 mL, 1.3 mmol). The reaction mixture was stirred at about 0° C. for about 1 h. The resulting solution was added dropwise to a solution of 3-ethyl-4-(6-((2-(trimethylsilyl)ethoxy)methyl)-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentanone (0.350 g, 0.876 mmol, Example #35 Step G) in THF (4 mL) at about 0° C. The reaction mixture was maintained at about 4° C. in a refrigerator for about 48 h. The reaction mixture was partitioned between water (5 mL) and DCM (5 mL) The layers were separated and the aqueous solution was extracted with DCM (2×5 mL). The combined organic extracts were concd under reduced pressure. The product was purified by silica gel chromatography eluting with a gradient of 0-2% MeOH/DCM, then by RP-HPLC (Table 1, Method 1) to give 3-ethyl-1-(morpholinosulfonylmethyl)-4-(6-((2-(trimethylsilyl)ethoxy)methyl)-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentanol (0.17 g, 34%) as a yellow oil: LC/MS (Table 1, Method b) Rt=2.32 & 2.42 min; MS m/z: 565 (M+H)+.

Provenance & Evidence