Potassium Carbonate → tert-butyl 3-{[3-(3-chloro-5-cyanophenoxy)-2-oxo-4-(trifluoromethyl)pyridin-1(2H)-yl]methyl}-1H-pyrazolo[3,4-b]pyridine-1-carboxylate

HRID 1952360Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1952360
[Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([O:10][C:11]2[C:12](=[O:21])[NH:13][CH:14]=[CH:15][C:16]=2[C:17]([F:20])([F:19])[F:18])[CH:9]=1)[C:5]#[N:6].C(=O)([O-])[O-].[K+].[K+].Br[CH2:29][C:30]1[C:38]2[C:33](=[N:34][CH:35]=[CH:36][CH:37]=2)[N:32]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[N:31]=1>CN(C)C=O.O.CO>[Cl:1][C:2]1[CH:9]=[C:8]([CH:7]=[C:4]([C:5]#[N:6])[CH:3]=1)[O:10][C:11]1[C:12](=[O:21])[N:13]([CH2:29][C:30]2[C:38]3[C:33](=[N:34][CH:35]=[CH:36][CH:37]=3)[N:32]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[N:31]=2)[CH:14]=[CH:15][C:16]=1[C:17]([F:18])([F:19])[F:20]

Komponenten

7

Edukt 3

HCID 11430Potassium CarbonateHCID 10828872tert-Butyl 3-(bromomethyl)-1H-pyrazolo[3,4-b]pyridine-1-carboxylateHCID 584600483-Chloro-5-((1,2-dihydro-2-oxo-4-(trifluoromethyl)-3-pyridinyl)oxy)benzonitrile

Produkt 1

HCID 68508502tert-butyl 3-{[3-(3-chloro-5-cyanophenoxy)-2-oxo-4-(trifluoromethyl)pyridin-1(2H)-yl]methyl}-1H-pyrazolo[3,4-b]pyridine-1-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 887MethanolLösungsmittelHCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel2×

Versuchsvorschrift

To a flask charged with 3-chloro-5-{[2-oxo-4-(trifluoromethyl)-1,2-dihydropyridin-3-yl]oxy}benzonitrile (3C, 2.03 g, 6.45 mmol) and potassium carbonate (0.891 g, 6.45 mmol) was added dimethylformamide (20 mL). To this under N2 was added tert-butyl 3-(bromomethyl)-1H-pyrazolo[3,4-b]pyridine-1-carboxylate (2.01 g, 6.45 mmol) as a solution in dimethylformamide (10 mL). This was allowed to stir at room temperature for 16 hours. After this time the reaction mixture was diluted with water (50 mL) and the mixture was extracted with ethyl acetate (2×100 mL). The combined organic fractions were washed with brine (3×100 mL), dried (MgSO4), filtered and the solvent was evaporated under reduced pressure. The resulting residue was purified by column chromatography on a pre-packed silica gel Redi Sep 120 gram column, eluting with 0-5% methanol in CH2Cl2 to give a solid. This was suspended in methanol (100 mL) and filtered to recover the title compound as a solid. 1H NMR (DMSO-d6) δ 8.71 (d, J=4.4 Hz, 1H), 8.23 (d, J=8.0 Hz, 1H), 8.11 (d, J=7.1 Hz, 1H), 7.74-7.70 (m, 1H), 7.56-7.52 (m, 1H), 7.50-7.45 (m, 1H), 7.44-7.38 (m, 1H), 6.70 (d, J=7.1 Hz, 1H), 5.59 (s, 2H), 1.62 (s, 9H). LRMS (M+1)=545.8.

Aufarbeitung

  1. extractionthe mixture was extracted with ethyl acetate (2×100 mL)
  2. washThe combined organic fractions were washed with brine (3×100 mL)
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. customthe solvent was evaporated under reduced pressure
  6. customThe resulting residue was purified by column chromatography on a pre-packed silica gel Redi Sep 120 gram column
  7. washeluting with 0-5% methanol in CH2Cl2
  8. customto give a solid
  9. filtrationfiltered
  10. customto recover the title compound as a solid

Quellen und Nachweise

ORD-Eintrag
ord-7f83c882edf54d7ba01eebd0e1b3d66d
Quelldatensatz
uspto-grants-2013_03
Patentnummer
US08404856B2

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