Sodium Carbonate → tert-butyl 4-(4-(6-amino-5-bromopyridin-3-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate

HRID 1926220

Reaktionsgleichung

Reaktionsgleichung von HRID 1926220
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[CH:18]=[C:17]([C:19]3[CH:20]=[N:21][C:22]([NH2:25])=[CH:23][CH:24]=3)[CH:16]=[N:15]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([O-])([O-])=O.[Na+].[Na+].[Br:32]Br.S([O-])([O-])(=O)=S.[Na+].[Na+].C(=O)(O)[O-].[Na+]>C(Cl)Cl.O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[CH:18]=[C:17]([C:19]3[CH:20]=[N:21][C:22]([NH2:25])=[C:23]([Br:32])[CH:24]=3)[CH:16]=[N:15]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Komponenten

8

Edukt 5

HCID 10340Sodium CarbonateHCID 24408BromineHCID 24477Sodium ThiosulfateHCID 516892Sodium BicarbonateHCID 675215374-[4-(6-Aminopyridin-3-yl)-pyrazol-1-yl]-piperidine-1-carboxylic acid tert-butyl ester

Produkt 1

HCID 67366272tert-butyl 4-(4-(6-amino-5-bromopyridin-3-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6344DichloromethaneLösungsmittel2×

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a well stirred solution of 4-[4-(6-aminopyridin-3-yl)-pyrazol-1-yl]-piperidine-1-carboxylic acid tert-butyl ester (24.4 g, 71.1 mmol) in DCM (800 mL) was added solid Na2CO3 (11.2 g, 107 mmol), and the mixture was cooled to 0° C. A solution of bromine (3.6 mL, 71 mmol) in DCM (200 mL) was added dropwise during 30 min, and the reaction mixture was stirred for further 5 h at ambient temperature. The reaction mixture was then cooled to 10° C., and a cold solution of 10% sodium thiosulfate in water (100 mL) followed by saturated sodium bicarbonate solution (100 mL) was added. After stirring for 10 min, the organic layer was separated, washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure to yield a brown solid. It was triturated twice with tert-butyl methyl ether (100 mL) at 40-45° C., filtered, and dried in vacuo to yield the title compound as white solid. 1H NMR (300 MHz, CDCl3): δ=1.48 (s, 9H), 1.92-1.96 (m, 2H), 2.13-2.17 (m, 2H), 2.89 (m, 2H), 4.23-4.28 (m, 3H), 4.86 (s, broad, 2H), 7.56 (s, 1H), 7.66 (s, 1H), 7.75 (d, 1H, J=2.1 Hz), 8.15 (d, 1H, J=2.1 Hz).

Aufarbeitung

  1. temperatureThe reaction mixture was then cooled to 10° C.
  2. additionwas added
  3. stirringAfter stirring for 10 min
  4. customthe organic layer was separated
  5. washwashed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customto yield a brown solid
  10. customIt was triturated twice with tert-butyl methyl ether (100 mL) at 40-45° C.
  11. filtrationfiltered
  12. customdried in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-6e6a3c2824a2444f98d79291ac973ff0
Quelldatensatz
uspto-grants-2012_05
Patentnummer
US08178668B2

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