Scheme 2.

Synthesis of 3-bromopyridine 14. Reagents and conditions: (i) Br₂ (0.9 eq.), 20% oleum, 165 °C, 24 h, 11 (12%), 12 (22%), 13 (35%); (ii) KMnO₄ (5 eq.), NaOH (0.7 eq.), H₂O, 110 °C, 3 h; (iii) cat. H₂SO₄, MeOH, reflux, 24 h, 53%; (iv) n-BuLi (1.1 eq.), THF, −78 °C, 1 h, or i-PrMgCl (1.1 eq.), THF, RT; then MeOH workup; (v) tetrahydropyran-2-ol (1.1 eq.), PPh₃ (1.1 eq.), diisopropyl azodicarboxylate (1.1 eq.), RT, 2 h, 46%;²³ (vi) methoxymethyl chloride (1.05 eq.), KO^tBu (1.1 eq.), DMF–CH₃CN, RT, 1 h;²⁶ (vii) base (1.5 eq.), then excess CO₂(s); base (1.5 eq.), then excess CO₂(s); then HCl/dioxane; *Ratios as determined by ¹H NMR.