Cesium fluoride → Tert-butyl 6-[4-({[6-(3-fluorophenyl)pyridin-3-yl]carbonyl}amino)piperidin-1-yl]nicotinate

HRID 602088

Reaktionsgleichung

Reaktionsgleichung von HRID 602088
[F:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:22]=[CH:21][C:11]([C:12]([NH:14][CH:15]3[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]3)=[O:13])=[CH:10][N:9]=2)[CH:5]=[CH:6][CH:7]=1.Br[C:24]1[CH:36]=[CH:35][C:27]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])=[CH:26][N:25]=1.[F-].[Cs+]>CC(N(C)C)=O>[F:1][C:2]1[CH:3]=[C:4]([C:8]2[N:9]=[CH:10][C:11]([C:12]([NH:14][CH:15]3[CH2:16][CH2:17][N:18]([C:24]4[CH:36]=[CH:35][C:27]([C:28]([O:30][C:31]([CH3:32])([CH3:33])[CH3:34])=[O:29])=[CH:26][N:25]=4)[CH2:19][CH2:20]3)=[O:13])=[CH:21][CH:22]=2)[CH:5]=[CH:6][CH:7]=1

Komponenten

5

Edukt 3

HCID 25953Cesium fluorideHCID 26369925(tert-Butyl) 6-bromonicotinateHCID 672679066-(3-fluorophenyl)-N-(piperidin-4-yl)nicotinamide

Produkt 1

HCID 59743962Tert-butyl 6-[4-({[6-(3-fluorophenyl)pyridin-3-yl]carbonyl}amino)piperidin-1-yl]nicotinateAusbeute 97 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 31374DimethylacetamideLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To a microwave tube was added 6-(3-fluorophenyl)-N-(piperidin-4-yl)nicotinamide (2.2 g, 7.35 mmol, tert-butyl 6-bromonicotinate (2.85 g, 11 mmol), DMA (5 mL), CsF(6.70 g, 44.1 mmol) and TEA (5 drops). After heating the reaction mixture on CEM microwave at fullpower (100° C. for 45 min), the solution was extracted with ethyl acetate and washed with water. The solvent was removed and the residue purified by chromatography (silica, 50% EtOAc: Hep) to give the desired product, tert-butyl 6-[4-({[6-(3-fluorophenyl)pyridin-3-yl]carbonyl}amino)piperidin-1-yl]nicotinate (3.39 g, 97%). 1H NMR (400 MHz, DMSO-d6) □ ppm 9.06 (1H, d, J=1.1 Hz), 8.58 (1H, d, J=1.6 Hz), 8.47 (1H, d, J=7.9 Hz), 8.27 (1H, d, J=8.4 Hz), 8.10 (1H, d, J=8.2 Hz), 7.98 (1H, d, J=8.4 Hz), 7.93 (1H, d, J=10.8 Hz), 7.86 (1H, d, J=9.1 Hz), 7.54 (1H, q), 7.29 (1H, t, J=8.6 Hz), 6.88 (1H, d, J=9.1 Hz), 4.41 (2H, d, J=13.5 Hz, 4.15 (1H, d, J=4.8 Hz), 3.10 (2H, t, J=12.3 Hz), 2.48 (2H, br. s.), 1.91 (2H, d, J=13.4 Hz), 1.50 (9H, s), HRMS (TOF, ES+) calculated 477.2302; observed 477.2515.

Aufarbeitung

  1. extractionthe solution was extracted with ethyl acetate
  2. washwashed with water
  3. customThe solvent was removed
  4. customthe residue purified by chromatography (silica, 50% EtOAc: Hep)

Quellen und Nachweise

ORD-Eintrag
ord-8108179a80d5444bb634f1cc4a6adf0a
Quelldatensatz
uspto-grants-2011_03
Patentnummer
US07902373B2

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