Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate → 4-Cyano-4-[(5-methyl-pyridine-3-carbonyl)-amino]-piperidine-1-carboxylic acid tert-butyl ester

Temperatur

40 °C

To a solution of 4-amino-4-cyano-piperidine-1-carboxylic acid tert-butyl ester (0.485 g, 2.15 mmol, 1.0 equiv; prepared as described in WO 03/104 236 A1 (Bristol-Myers Squibb Company); [CAS RN 331281-25-5]) in anhydrous THF (11 mL) and N-ethyl diisopropylamine (0.44 mL) was added in the presence of (benzotriazol-1-yloxy)-tris-(dimethylamino)phosphonium hexafluorophosphate (1.047 g, 2.37 mmol, 1.1 equiv; BOP reagent) 5-methyl-nicotinic acid (0.295 g, 2.15 mmol, 1.0 equiv) and the reaction mixture stirred at 40° C. during a weekend. The reaction mixture was poured on crashed ice/NH4Cl, extracted with ethyl acetate (2×200 mL) and the combined organic phases washed with a sat. solution of NaCl (2×100 mL) and water (2×100 mL). The organic phase was dried over Na2SO4, concentrated by evaporation under reduced pressure and the crude material purified by silica column chromatography eluting with a mixture of ethyl acetate/triethylamine (97:3) providing 0.48 g (65%) of the title compound as off-white foam. MS (ISP): 345.3 [M+H]+

1. additionThe reaction mixture was poured
2. extractionextracted with ethyl acetate (2×200 mL)
3. washthe combined organic phases washed with a sat. solution of NaCl (2×100 mL) and water (2×100 mL)
4. dry with materialThe organic phase was dried over Na2SO4
5. concentrationconcentrated by evaporation under reduced pressure
6. customthe crude material purified by silica column chromatography
7. washeluting with a mixture of ethyl acetate/triethylamine (97:3)

ORD-Eintrag

ord-41949de553fa428e87290db816feb1dd

Quelldatensatz

uspto-grants-2011_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08026365B2