Cesium carbonate → 3-chloro-5-{[5-chloro-1-(1H-pyrazolo[3,4-b]pyridin-3-ylmethyl)-1H-benzimidazol-4-yl]oxy}benzonitrile dihydrochloride

HRID 505531Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 505531
[Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([O:10][C:11]2[C:19]3[N:18]=[CH:17][NH:16][C:15]=3[CH:14]=[CH:13][C:12]=2[Cl:20])[CH:9]=1)[C:5]#[N:6].Br[CH2:22][C:23]1[C:31]2[C:26](=[N:27][CH:28]=[CH:29][CH:30]=2)[N:25](C(OC(C)(C)C)=O)[N:24]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.O>[ClH:1].[ClH:1].[Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([O:10][C:11]2[C:19]3[N:18]=[CH:17][N:16]([CH2:22][C:23]4[C:31]5[C:26](=[N:27][CH:28]=[CH:29][CH:30]=5)[NH:25][N:24]=4)[C:15]=3[CH:14]=[CH:13][C:12]=2[Cl:20])[CH:9]=1)[C:5]#[N:6]

Komponenten

6

Edukt 3

HCID 10796Cesium carbonateHCID 10828872tert-Butyl 3-(bromomethyl)-1H-pyrazolo[3,4-b]pyridine-1-carboxylateHCID 684255163-chloro-5-[(5-chloro-1H-benzimidazol-4-yl)oxy]benzonitrile

Produkt 1

HCID 1784786843-chloro-5-{[5-chloro-1-(1H-pyrazolo[3,4-b]pyridin-3-ylmethyl)-1H-benzimidazol-4-yl]oxy}benzonitrile dihydrochloride

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a suspension of 3-chloro-5-[(5-chloro-1H-benzimidazol-4-yl)oxy]benzonitrile (101 mg, 0.332 mmol) and tert-butyl 3-(bromomethyl)-1H-pyrazolo[3,4-b]pyridine-1-carboxylate (104 mg, 0.332 mmol) in DMF (1 mL) was added cesium carbonate (216 mg, 0.664 mmol) and the suspension was stirred at room temperature for 2.25 hours. This mixture was diluted with water (10 mL) and extracted with ethyl acetate (2×12 mL). The combined extracts were washed with water, dried over MgSO4, filtered and evaporated in vacuo. This residue was purified on silica gel (40 g) column eluting with 0-100% ethyl acetate/methylene chloride. The fractions corresponding to the desired Boc protected product were combined and the solvent removed in vacuo. This residue was redissolved in TFA (3 mL) and allowed to stand at room temperature for 10 minutes. The solvent was removed in vacuo and the residue was purified on silica gel (4 g) column eluting with 0-10% methanol/methylene chloride gradient. The pure fractions were combined, treated with 1N hydrochloric acid and the solvent removed in vacuo to provide title compound. 1H NMR (DMSO-d6): δ 13.7 (s, 1H), 8.58 (s, 1H), 8.52 (d, 1H, J=4.4 Hz), 8.16 (d, 1H, 8.0 Hz), 7.74 (dd, 1H, J=1.5 Hz), 7.63 (d, 1H, J=8.8 Hz), 7.47 (d, 1H, J=8.5 Hz), 7.39 (dd, 1H, J=1.5 Hz), 7.29 (dd, 1H, J=2 Hz), 7.19 (dd, 1H, J=4.5 and 8.1 Hz) and 5.92 (s, 2H) ppm. LRMS (M+1)=434.7

Aufarbeitung

  1. extractionextracted with ethyl acetate (2×12 mL)
  2. washThe combined extracts were washed with water
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. customevaporated in vacuo
  6. customThis residue was purified on silica gel (40 g) column
  7. washeluting with 0-100% ethyl acetate/methylene chloride
  8. customthe solvent removed in vacuo
  9. dissolutionThis residue was redissolved in TFA (3 mL)
  10. waitto stand at room temperature for 10 minutes
  11. customThe solvent was removed in vacuo
  12. customthe residue was purified on silica gel (4 g) column
  13. washeluting with 0-10% methanol/methylene chloride gradient
  14. additiontreated with 1N hydrochloric acid
  15. customthe solvent removed in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-2709b1361e2c49cc87e7fae41bf8924a
Quelldatensatz
uspto-grants-2010_08
Patentnummer
US07781454B2

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