Diisopropylethylamine → tert-butyl (3S)-3-[(2-chloro-5-fluoro-pyrimidin-4-yl)amino]piperidine-1-carboxylate

HRID 74870

Reaktionsgleichung

[NH2:1][C@H:2]1[CH2:7][CH2:6][CH2:5][N:4]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:3]1.[Cl:15][C:16]1[N:21]=[C:20](Cl)[C:19]([F:23])=[CH:18][N:17]=1.C(N(C(C)C)CC)(C)C>C(O)(C)C>[Cl:15][C:16]1[N:21]=[C:20]([NH:1][C@H:2]2[CH2:7][CH2:6][CH2:5][N:4]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:3]2)[C:19]([F:23])=[CH:18][N:17]=1

Komponenten

Reaktionsbedingungen

Temperatur: 80 °C

Versuchsvorschrift

To a solution of tert-butyl (3S)-3-aminopiperidine-1-carboxylate (8.1 g, 40.4 mmol) and 2,4-dichloro-5-fluoro-pyrimidine (6.6 g, 39.8 mmol) in isopropanol (80 mL) was added N,N-diisopropyl-N-ethylamine (9.0 mL, 51.7 mmol). The reaction mixture was warmed to 80° C. and stirred for 17 hours. All volatiles were removed at reduced pressure and the residue was dissolved in EtOAc. The organic layer was partitioned with water and the layers were separated. The organic phase was washed with brine, dried (MgSO4), filtered and concentrated in vacuo. The resulting residue was dissolved in CH2Cl2 and purified by silica gel chromatography (0-50% EtOAc/Hexanes) to afford the desired product, 5a.

Aufarbeitung

customAll volatiles were removed at reduced pressure
dissolutionthe residue was dissolved in EtOAc
customThe organic layer was partitioned with water
customthe layers were separated
washThe organic phase was washed with brine
dry with materialdried (MgSO4)
filtrationfiltered
concentrationconcentrated in vacuo
dissolutionThe resulting residue was dissolved in CH2Cl2
custompurified by silica gel chromatography (0-50% EtOAc/Hexanes)

Quellen und Nachweise

ORD-Eintrag: ord-910471e5d46f4d8b857cb7c1c32da199
Quelldatensatz: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patentnummer: US08829007B2

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