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Cesium carbonate → N-{6-[2-(2,6-Dichlorophenyl)-7-fluoro-2H-pyrazolo[4,3-c]pyridin-4-ylamino]-pyrimidin-4-yl}-acetamide

HRID 626749
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 626749
Br[C:2]1[C:7]2=[CH:8][N:9]([C:11]3[C:16]([Cl:17])=[CH:15][CH:14]=[CH:13][C:12]=3[Cl:18])[N:10]=[C:6]2[C:5]([F:19])=[CH:4][N:3]=1.[NH2:20][C:21]1[N:26]=[CH:25][N:24]=[C:23]([NH:27][C:28](=[O:30])[CH3:29])[CH:22]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:18][C:12]1[CH:13]=[CH:14][CH:15]=[C:16]([Cl:17])[C:11]=1[N:9]1[CH:8]=[C:7]2[C:2]([NH:20][C:21]3[N:26]=[CH:25][N:24]=[C:23]([NH:27][C:28](=[O:30])[CH3:29])[CH:22]=3)=[N:3][CH:4]=[C:5]([F:19])[C:6]2=[N:10]1
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

7

Edukt 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 3031498N-(6-aminopyrimidin-4-yl)acetamideHCID 866970564-Bromo-2-(2,6-dichlorophenyl)-7-fluoro-2H-pyrazolo[4,3-c]pyridine

Produkt 1

HCID 69671310N-{6-[2-(2,6-Dichlorophenyl)-7-fluoro-2H-pyrazolo[4,3-c]pyridin-4-ylamino]-pyrimidin-4-yl}-acetamide
Ausbeute 10 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
150 °C

Versuchsvorschrift

A mixture of 4-bromo-2-(2,6-dichlorophenyl)-7-fluoro-2H-pyrazolo[4,3-c]pyridine (320 mg, 0.89 mmol), N-(6-aminopyrimidin-4-yl)-acetamide (152 mg, 1.0 mmol), Pd2(dba)3 (20 mg, 0.022 mmol), Xantphos (52 mg, 0.089 mmol) and cesium carbonate (580 mg, 1.78 mmol) in dioxane (10 mL) was de-gassed and purged with nitrogen and the reaction mixture was heated at 150° C. in the microwave for 1 h. The resultant mixture was partitioned between ethyl acetate and water and the layers were separated. The organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (80-100% ethyl acetate in cyclohexane) to afford an off-white solid. This was re-purified by HPLC [gradient: 5 to 98% acetonitrile (0.1% ammonium hydroxide) in water (0.1% ammonium hydroxide)], to afford the title compound as a white solid (31 mg, 10% yield). 1H NMR (400 MHz, DMSO-d6): δ 10.65-10.61 (m, 2H), 9.26 (d, J=2.6 Hz, 1H), 9.08 (d, J=1.1 Hz, 1H), 8.53 (d, J=1.1 Hz, 1H), 7.92 (d, J=3.4 Hz, 1H), 7.83-7.81 (m, 2H), 7.74 (dd, J=9.1, 7.3 Hz, 1H), 2.14 (s, 3H). LCMS (Method B): RT=3.20 min, m/z: 432 [M+H+].

Aufarbeitung

  1. customwas de-gassed
  2. custompurged with nitrogen
  3. customThe resultant mixture was partitioned between ethyl acetate and water
  4. customthe layers were separated
  5. washThe organic layer was washed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel flash chromatography (80-100% ethyl acetate in cyclohexane)
  10. customto afford an off-white solid
  11. customThis was re-purified by HPLC [gradient: 5 to 98% acetonitrile (0.1% ammonium hydroxide) in water (0.1% ammonium hydroxide)]

Quellen und Nachweise

ORD-Eintrag
ord-05661be5b41b485cb3732df591ccaa77
Quelldatensatz
uspto-grants-2016_04
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US09309240B2

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