1,1'-Carbonyldiimidazole → N'-({2-[5-(4-fluorobenzyl)-3-pyridin-4-yl-1H-pyrazol-1-yl]acetyl}oxy)pyrimidine-2-carboximidamide

Participants

Reaction Steps

To a suspension of [5-(4-fluorobenzyl)-3-pyridin-4-yl-1H-pyrazol-1-yl]acetic acid (200 mg, 0.64 mmol) in THF (2 mL) and DMF (2 mL) was added CDI (240 mg, 1.41 mmol) and stirred for 2 hours forming a clear solution. To this was added N′-hydroxypyrimidine-2-carboximidamide (115 mg, 0.84 mmol) and the resulting suspension stirred for 18 hours at room temperature. The solid was filtered off to yield crude N′-({2-[5-(4-fluorobenzyl)-3-pyridin-4-yl-1H-pyrazol-1-yl]acetyl}oxy)pyrimidine-2-carboximidamide, and suspended in THF (2 mL) and a solution of TBAF (1 M in THF, 0.64 mL, 0.64 mmol) was added and the mixture stirred for 15 minutes at room temperature. The volatiles were then removed in vacuo and the residue purified by Biotage flash chromatography, eluting with 2-6% MeOH/DCM to afford the title compound as a waxy white solid, 100 mg, 37%. 1H NMR (400 MHz, DMSO-D6) δ ppm 9.00 (d, 2 H), 8.56 (d, 2 H), 7.68-7.73 (m, 3 H), 7.27-7.33 (m, 2 H), 7.05 (t, 2 H), 6.77 (s, 1 H), 6.00 (s, 2 H), 4.18 (s, 2 H); m/z (APCI+) for C22H16N7FO 414.1 (M+H)+.

Provenance & Evidence