Isopropanol → 6-Amino-4-isopropoxynicotinonitrile

Participants

Reaction Steps

A solution of KHMDS (87 g, 438 mmol) was added portionwise to a solution of propan-2-ol (26.3 g, 438 mmol) in THF (250 ml) at room temperature. After 15 min a solution of 6-amino-4-fluoronicotinonitrile (intermediate 21, 30 g, 219 mmol) in THF (200 ml) was added and the reaction mixture stirred for 18 h at room temperature. The reaction mixture was partitioned between saturated aqueous NH4Cl and EtOAc, extracted with EtOAc (2×), the combined EtOAc layers were dried over Na2SO4 and evaporated. The residue was triturated with Et2O and the product obtained by filtration as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 8.12 (s, 1H), 6.82 (s, 2H), 6.07 (s, 1H), 4.64 (septet, 1H), 1.31 (d, 6H). (UPLC-MS 7) tR 0.61; ESI-MS 178.1 [M+H]+.

Provenance & Evidence