N,N-Dimethylglycine → 5-(4-fluorophenyl)-2-(pyridin-3-yloxymethyl)-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one

HRID 2046210Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2046210
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]3[N:14]=[C:15]([CH2:17][OH:18])[CH:16]=[C:10]3[C:9]2=[O:19])=[CH:4][CH:3]=1.Br[C:21]1[CH:22]=[N:23][CH:24]=[CH:25][CH:26]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CN(C)CC(O)=O>O1CCOCC1.CCOC(C)=O.[Cu]I>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]3[N:14]=[C:15]([CH2:17][O:18][C:21]4[CH:22]=[N:23][CH:24]=[CH:25][CH:26]=4)[CH:16]=[C:10]3[C:9]2=[O:19])=[CH:4][CH:3]=1

Komponenten

8

Edukt 4

HCID 673N,N-Dimethylglycine2×HCID 10796Cesium carbonate2×HCID 122863-BromopyridineHCID 679743405-(4-Fluoro-phenyl)-2-hydroxymethyl-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one

Produkt 1

HCID 574101415-(4-fluorophenyl)-2-(pyridin-3-yloxymethyl)-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-oneAusbeute 11 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Katalysator2×HCID 8857Ethyl AcetateLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

Copper (I) iodide (7.3 mg, 0.038 mmol) was added to a stirred suspension of 5-(4-fluoro-phenyl)-2-hydroxymethyl-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one (50 mg, 0.19 mmol), 3-bromopyridine (0.073 mL, 0.76 mmol), cesium carbonate (0.25 g, 0.77 mmol) and N,N-dimethylglycine (7.89 mg, 0.077 mmol) in 1,4-dioxane (1 mL) in a sealed tube and under nitrogen. The mixture was stirred at 100° C. for 16 hours. More copper (I) iodide (7.3 mg, 0.038 mmol) was added, N,N-dimethylglycine (7.89 mg, 0.077 mmol), cesium carbonate (0.25 g, 0.77 mmol) 3-bromopyridine (0.073 mL, 0.76 mmol) were added and the mixture was stirred at 130° C. for another 24 hours. The mixture was diluted with AcOEt and washed with a 16% aqueous solution of NH4OH. The organic layer was separated, dried (MgSO4), filtered and the solvents evaporated in vacuo. The crude product was purified by flash column chromatography (silica; 7 M solution of ammonia in MeOH in DCM 0/100 to 5/95). The desired fractions were collected and the solvents evaporated in vacuo to yield 5-(4-fluorophenyl)-2-(pyridin-3-yloxymethyl)-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one (7 mg, 11% yield) as a yellow solid. 1H NMR (500 MHz, CDCl3) δ ppm 4.13-4.22 (m, 2H), 4.55 (dd, J=6.8, 5.3 Hz, 2H), 5.17 (s, 2H), 7.03 (s, 1H), 7.10-7.18 (m, 2H), 7.23 (dd, J=8.5, 4.8 Hz, 1H), 7.28-7.36 (m, 3H), 8.25 (dd, J=4.6, 1.2 Hz, 1H), 8.41 (d, J=2.9 Hz, 1H).

Aufarbeitung

  1. stirringthe mixture was stirred at 130° C. for another 24 hours
  2. washwashed with a 16% aqueous solution of NH4OH
  3. customThe organic layer was separated
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customthe solvents evaporated in vacuo
  7. customThe crude product was purified by flash column chromatography (silica; 7 M solution of ammonia in MeOH in DCM 0/100 to 5/95)
  8. customThe desired fractions were collected
  9. customthe solvents evaporated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-8d34fac4b71c436ea08008038d99e6b2
Quelldatensatz
uspto-grants-2013_11
Patentnummer
US08592422B2

Notizen zur Reaktion

Wird geladen…