2,4-Dichloropyrimidine → tert-Butyl 4-((2-chloropyrimidin-4-yl)amino)piperidine-1-carboxylate

HRID 2242963Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2242963
[Cl:1][C:2]1[N:7]=[C:6](Cl)[CH:5]=[CH:4][N:3]=1.[C:9]([O:13][C:14]([N:16]1[CH2:21][CH2:20][CH:19]([NH2:22])[CH2:18][CH2:17]1)=[O:15])([CH3:12])([CH3:11])[CH3:10]>CN(C=O)C>[C:9]([O:13][C:14]([N:16]1[CH2:21][CH2:20][CH:19]([NH:22][C:6]2[CH:5]=[CH:4][N:3]=[C:2]([Cl:1])[N:7]=2)[CH2:18][CH2:17]1)=[O:15])([CH3:12])([CH3:10])[CH3:11]

Komponenten

4

Edukt 2

HCID 775312,4-DichloropyrimidineHCID 12682914-Amino-1-Boc-piperidine

Produkt 1

HCID 22309647tert-Butyl 4-((2-chloropyrimidin-4-yl)amino)piperidine-1-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

A mixture of 2,4-dichloro-pyrimidine (4.0 g, 26.85 mmol, 1.0 equiv; commercially available) and 4-amino-piperidine-1-carboxylic acid tert-butyl ester (6.45 g, 32.22 mmol, 1.2 equiv) in anhydrous DMF (100 mL) was stirred at rt for 18 h. The organic phase was concentrated under reduced pressure and the crude reaction mixture purified with silica column chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of heptane/ethyl acetate providing 3.2 g (38%) of the title compound. 1H NMR (400 MHz, CDCl3): δ1.35-1.45 (m, 2H), 1.47 (s, 9H), 1.99-2.03 (m, 2H), 2.91-2.97 (m, 2H), 3.81-3.90 (m, 1H), 4.04-4.07 (br d, 2H), 5.33 (d, J=8.0 Hz, 1H), 6.25 (d, J=4.0 Hz, 1H), 7.98 (d, J=4.0 Hz, 1H). 13C NMR (75 MHz, DMSO): δ 28.05, 30.94, 42.04, 46.69, 78.64, 105.13, 153.86, 155.57, 159.81, 162.72. MS (ISP): 313.1 [M+H]+.

Aufarbeitung

  1. concentrationThe organic phase was concentrated under reduced pressure
  2. customthe crude reaction mixture
  3. custompurified with silica column chromatography
  4. washeluting with a gradient of heptane/ethyl acetate providing 3.2 g (38%) of the title compound

Quellen und Nachweise

ORD-Eintrag
ord-813307e5e34e4abe988a0e703607cec5
Quelldatensatz
uspto-grants-2010_03
Patentnummer
US07674804B2

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