2-cyclopropyl-4-Methylpyridin-3-aMine synthesis

Yield:-

Reaction Conditions:

with caesium carbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂ in tetrahydrofuran;water at 80;Inert atmosphere;Sealed tube;

Steps:

6
PREPARATIVE EXAMPLE 6; 2-Cvclopropyl-4-methylpyridin-3-amine (FFl); Following a modified synthetic procedure reported in J. Org. Chem. 2003, 68, 5534, a mixture of 2-bromo-4-methylpyridin-3-amine (1.0 eq.), potassium cyclopropyltrifluoroborate (2.0 eq.), Cs₂CO₃ (3.0 eq.) and PdCl₂(dppf)-CH₂Cl₂ adduct (0.1 eq.) in 10:1 solution THF:H₂O (0.14M) was put in a 10-mL glass vial equipped with a small magnetic stirring bar. The reaction vessel was fitted with a rubber septum, was evacuated and back-filled with argon and sealed with an aluminum/Teflon crimp top. The reaction mixture was then heated for O/N at 80 ⁰C. After completion of the reaction, the vial was cooled to RT before it was opened. The reaction mixture was diluted with EtOAc and filtered on a pad of Solca Floc200FCC. The crude product was purified by flash chromatography eluting with 10-100% EtO Ac/petroleum ether affording the titled compound as brown oil. ¹H-NMR (400 MHz, DMSO-d₆, 300K) δ 7.55 (IH, d, J = 4.7 Hz), 6.75 (IH, d, J = 4.7 Hz), 4.89 (2H, br. s), 2.13-2.04 (4H, m), 0.85-0.68 (4H, m). MS (ES) C₉Hi₂N₂ requires: 148, found: 149 (M+H)⁺.

References:

ISTITUTO DI RICERCHE DI BIOLOGIA MOLECOLARE P. ANGELETTI S.P.A.;BRANCA, Danila;FERRIGNO, Federica;HERNANDO, Jose, Ignacio, Martin;JONES, Philip;KINZEL, Olaf;MALANCONA, Savina;MURAGLIA, Ester;PALUMBI, Maria, Cecilia;PESCATORE, Giovanna;SCARPELLI, Rita WO2010/23480, 2010, A1 Location in patent:Page/Page column 43