Methanesulfonamide → N-((5-(4-cyano-3-methoxyphenyl)pyridin-3-yl)methyl)methanesulfonamide

Participants

Reaction Conditions

Reaction Steps

(General reductive amination procedure): Titanium(IV) isopropoxide (0.098 ml, 0.336 mmol) was added dropwise to a mixture of 4-(5-formyl-pyridin-3-yl)-2-methoxy-benzonitrile (40 mg, 0.168 mmol) and methanesulfonamide (23.96 mg, 0.252 mmol) in toluene (10 mL). The resulting mixture was heated to 140° C. (bath temperature) for 3 hr. After concentration, the residue was dissolved in CH2Cl2 (10 mL). NaBH(OAc)3 (107 mg, 0.504 mmol) was added at room temperature. The resulting mixture was stirred at room temperature overnight (18 h). The reaction was quenched by the addition of saturated NaHCO3 solution (10 mL). The mixture was filtered, and the organic layer was separated. The aqueous layer was extracted with CH2Cl2 (15 mL×3). The combined extracts were dried over Na2SO4. After filtration and concentration, the residue was purified by isco column (MeOH—CH2Cl2, v/v, 15 to 3%) and yielded a colorless solid (31 mg). HRMS 317.08431 M+, C15H15N3O3S requires 317.08341, ESI-MS m/z: 318.0 [M+H]+, 1H NMR (400 MHz, CDCl3) δ ppm 2.94 (s, 3H), 3.96 (s, 3H), 4.38 (d, J=6.3 Hz, 2H), 4.70 (m, 1H), 7.06 (d, J=1.24 Hz, 1H), 7.16 (m, 1H), 7.60 (d, J=8 Hz, 1H), 7.87 (s, 1H), 8.57 (d, J=2 Hz, 1H), 8.73 (d, J=2 Hz, 1H).

Provenance & Evidence