Fig 5.

Synthesis of intermediate 7. Reagents and conditions: (a) 2-bromoacetonitrile, Lithium bis(trimethylsilyl)amide solution 1.0 M in THF, THF, −78°C to room temperature, 2 h. (b) (i) H₂(g), Pt₂O, MeOH, room temperature, 24 h. (ii) MeOH, room temperature, 24 h. (c) 20% aq NaOH in MeOH: THF: H₂O (5:5:1), rt, 4 h. (d) Isobutyl chloroformate, THF, Et₃N, −30°C to 10°C, 1 h then CH₂N₂ in Et₂O, 0°C to room temperature, 16 h. (e) 33% HBr in H₂O, THF, −20°C. (f) Cesium fluoride, 2,6-dichlorobenzoic acid, THF. (g) 20% TFA in CH₂Cl₂, 0°C to room temperature, 2 h.