2-Chloro-4-fluorobenzoyl chloride → 2-Chloro-N-[6-(1-cyclopropylmethyl-piperidin-4-yloxy)-pyridin-2-yl]-4-fluoro-benzamide

Participants

Reaction Steps

Add 2-chloro-4-fluorobenzoyl chloride (149 mg, 0.58 mmol) to a solution of 6-(1-cyclopropylmethyl-piperidin-4-yloxy)-pyridin-2-ylamine (preparation 70, 130 mg, 0.53 mmol) in pyridine (7 mL) and beat at 55° C. for 15 hr. Remove pyridine in vacuo, dissolve the residue in CH2Cl2, wash with saturated NaHCO3 solution, dry over Na2SO4, filter and concentrate to give a residue. Chromatography (silica gel, eluting with 5% 2M NH3-Methanol in CH2Cl2) provides 170 mg (79%) of the title compound: mass spectrum (ion spray): 404.1 (M+1); 1H NMR (CDCl3, ppm): 8.08 (s, 1H), 7.63 (m, 2H), 7.52 (t, 1H), 7.11 (m, 1H), 6.99 (m, 1H), 6.41 (d, 1H), 4.82 (m, 1H), 2.72 (m, 2H), 2.26 (m, 2H), 2.17 (d, 2H), 1.89 (m, 2H), 1.69 (m, 2H), 0.77 (m, 1H), 0.40 (m, 2H), 0.00 (m, 2H). Hydrochloride salt: Analytical calc. for C21H23ClFN3O2.HCl.0.5H2O: C, 56.13; H, 5.61; N, 9.35. Found: C, 56.12; H, 5.30; N, 9.35.

Provenance & Evidence