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

Temperature

140 °C

(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).

1. concentrationAfter concentration
2. dissolutionthe residue was dissolved in CH2Cl2 (10 mL)
3. customThe reaction was quenched by the addition of saturated NaHCO3 solution (10 mL)
4. filtrationThe mixture was filtered
5. customthe organic layer was separated
6. extractionThe aqueous layer was extracted with CH2Cl2 (15 mL×3)
7. dry with materialThe combined extracts were dried over Na2SO4
8. filtrationAfter filtration and concentration
9. customthe residue was purified by isco column (MeOH—CH2Cl2, v/v, 15 to 3%)

ORD record

ord-990c0711119f46a295a22e1f7e8bde7d

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08809545B2