Diisopropylethylamine → HCID 20664172, compound

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Reaction Steps

Diisopropylethylamine (0.018 mL, 0.1 mmol) was added to a solution of 4-(3-benzyl-1-ethyl-(1H-pyrazol-5-yl))piperidine trifluoroacetate (37 mg, 0.1 mmol, from Example 1, Step C) in 0.5 mL of 1,2-dichloroethane (DCE). A solution of dihydro-3-(R)-(3-(R)-formyl-4-(S)-(3-fluorophenyl)-pyrrolidin-1-yl)-4,4-dimethyl-2(3H)furanone (25 mg, 0.082 mmol, from Step D) in 0.5 mL of DCE was then added, followed by a slurry of sodium triacetoxyborohydride (30 mg, 0.144 mmol) in 0.5 mL of DCE. The reaction mixture was mixed well, then allowed to stand at room temperature for 2 h. The mixture was concentrated and purified by preparative HPLC (column: YMC combiprep ODS-A 20×50 mm, gradient: 10% acetonitrile/water w/0.1% TFA to 100% acetonitrile/water w/0.1% TFA over 8 min, then ramp to 10% acetonitrile/water w/0.1% TFA over 2 min, flow: 20 mL/min), followed by conversion to the free base by solid phase extraction (column: Varian SCX, loading: methanol, elution: 2.0M ammonia in methanol) to afford 17.2 mg (37% yield) of the title compound. ESI-MS. M/z; (M+H)=559.7; HPLC A: 2.34 min.

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