Formic Acid → 6-[4-(3,6-Dihydro-4-phenyl-1(2H)-pyridinyl)-1-butynyl]-N-methyl-3-pyridinamine

Temperature

50 °C

To 0.50 mL (6.8 mmol) of acetic anhydride is added 0.32 mL (8.4 mmol) of 88% formic acid dropwise under nitrogen. Anhydrous tetrahydrofuran (10 mL) is added, and the solution is heated at 50° C. for 2 hours. To the cooled solution is added a suspension of 6-[4-(3,6-dihydro-4-phenyl-1(2H)-pyridinyl)-1-butynyl]-3-pyridinamine (Example 13) (0.8 g, 2.6 mmol) in 10 mL of tetrahydrofuran, and the solution is stirred at room temperature for 18 hours. The mixture is concentrated in vacuo, and the residue is partitioned between dichloromethane and 5% ammonium hydroxide. The organic layer is dried and concentrated in vacuo. The residue, in 10 mL of tetrahydrofuran, is added dropwise under nitrogen to a suspension of 0.14 g (3.9 mmol) of lithium aluminum hydride in 20 mL of dry tetrahydrofuran at 0° C. The reaction mixture is stirred at 0° C. for 5 hours. The reaction is quenched by sequential addition of 0.52 mL of 10% hydrochloric acid solution, 0.52 mL of 30% sodium hydroxide solution, and 0.52 mL of water. The resulting mixture is filtered through diatomaceous earth (Celite), evaporated in vacuo, and chromatographed (silica gel, 1% methanol/99% dichloromethane) to give the title compound, containing 0.5 mol of water; mp 164.5°-165.5° C.

1. additionTo the cooled solution is added
2. concentrationThe mixture is concentrated in vacuo
3. customthe residue is partitioned between dichloromethane and 5% ammonium hydroxide
4. customThe organic layer is dried
5. concentrationconcentrated in vacuo
6. stirringThe reaction mixture is stirred at 0° C. for 5 hours
7. customThe reaction is quenched by sequential addition of 0.52 mL of 10% hydrochloric acid solution, 0.52 mL of 30% sodium hydroxide solution, and 0.52 mL of water
8. filtrationThe resulting mixture is filtered through diatomaceous earth (Celite)
9. customevaporated in vacuo
10. customchromatographed (silica gel, 1% methanol/99% dichloromethane)

ORD record

ord-94b6ecaaa22f4ccdb0cd7c46171cf119

Source dataset

uspto-grants-1993_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05273977