Reaktion #2161289

ord-f565be3b09ea4dc4bc2fb1fa691937d6

Reaktionsgleichung

CC(C)(C)[Si](C)(C)OCCCBr
(3-bromopropoxy)(tert-butyl)dimethylsilane
Fc1ccc(Cc2cc(-c3ccncc3)n[nH]2)cc1
4-[5-(4-fluorobenzyl)-1H-pyrazol-3-yl]pyridine
[H-].[Na+]
NaH
CC(C)(C)[Si](C)(C)OCCCn1nc(-c2ccncc2)cc1Cc1ccc(F)cc1
4-(5-(4-fluorobenzyl)-1-(3-(tert-butyldimethylsilyloxy)propyl)-1H-pyrazol-3-yl)pyridine

Lösungsmittel

Reaktionsbedingungen

Temperatur
100°CELSIUS
Detaillierte Bedingungen
See reaction.notes.procedure_details.

Aufarbeitung

  1. 1
    SonstigeThe solvent was removed

Vorschrift

To a solution of 4-[5-(4-fluorobenzyl)-1H-pyrazol-3-yl]pyridine (0.5 g, 1.97 mmol) in DMF (10 mL) was added NaH (80 mg, 1.97 mmol) and the suspension was stirred for 20 minutes under nitrogen. This was followed by the addition of (3-bromopropoxy)(tert-butyl)dimethylsilane (457 μL, 1.97 mmol) and the reaction mixture was heated to 100° C. under nitrogen overnight. The solvent was removed to yield crude 4-(5-(4-fluorobenzyl)-1-(3-(tert-butyldimethylsilyloxy)propyl)-1H-pyrazol-3-yl)pyridine that was taken into THF (10 mL) at 0° C. and TBAF (1 M in THF, 1.97 mL, 1.97 mmol) was added. The mixture was stirred at 0° C. for 1 hour followed by stirring at room temperature for 1 hour. The solvent was removed and the residue was diluted with EtOAc and washed with H2O, brine, dried over MgSO4, filtered and concentrated. The residue was purified by flash chromatography (2-5% MeOH/CH2Cl2) then again using 3% MeOH/EtOAc followed by trituration with Et2O to yield the title compound as a white solid (0.33 g, 54%). 1H NMR (400 MHz, DICHLOROMETHANE-D2) δ ppm 8.55 (d, 2 H), 7.60 (d, 2 H), 7.16-7.24 (m, 2 H), 7.04 (t, 2 H), 6.40 (s, 1 H), 4.18 (t, 2 H), 4.03 (s, 2 H), 3.57 (t, 2 H), 1.87-1.96 (m, 2 H); m/z (APCI+) for C18H18N3FO 312.2 (M+H)+.

Quelle

DOI: 10.6084/m9.figshare.5104873.v1Patent: US07919488B2uspto-grants-2011_04