Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1) → 2-(1-Boc-piperidin-4-ylmethylamino)-5-chloro-N-(5-chloropyridin-2-yl)benzamide

Temperatur

70 °C

To a solution of 1-Boc-piperidine-4-carboxaldehyde (3.5 g, 14 mmol) and 2-amino-5-chloro-N-(5-chloropyridin-2-yl)benzamide (3.9 g, 14 mmol) in benzene (250 mL), a catalytic amount of pyridinium p-toluenesulfonate (0.35 g, 1.4 mmol) was added, followed by 4 A molecular sieves. The reaction mixture was heated at reflux for 48 h with azeotropic removal of water. The mixture was subsequently filtered through a pad of diatomaceous earth, washing well with ethyl acetate. The filtrate was concentrated in vacuo to a residue that was taken up in acetic acid (100 mL) and treated with borane-trimethylamine complex (3 g, 42 mmol). The mixture was heated at 70° C. for 24 h; then it was diluted with 2 N NaOH and extracted with dichloromethane. The water layer was neutralized with solid sodium bicarbonate, and further extracted with dichloromethane. The combined organic extracts were dried with MgSO4, filtered, and concentrated in vacuo to a solid residue (8 g, >100%) which was identified as the desired product and taken on directly to the next step without further purification.

1. temperatureThe reaction mixture was heated
2. filtrationThe mixture was subsequently filtered through a pad of diatomaceous earth
3. washwashing well with ethyl acetate
4. concentrationThe filtrate was concentrated in vacuo to a residue that
5. extractionextracted with dichloromethane
6. extractionfurther extracted with dichloromethane
7. dry with materialThe combined organic extracts were dried with MgSO4
8. filtrationfiltered
9. concentrationconcentrated in vacuo to a solid residue (8 g, >100%) which
10. customwithout further purification

ORD-Eintrag

ord-1982d584fa92472b9a674be5cd0ed14a

Quelldatensatz

uspto-grants-2006_10

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07129245B2