Cesium carbonate → Cyclopropanecarboxylic acid [2-(2-chloro-6-fluorophenyl)-2H-pyrazolo[4,3-c]pyridin-4-yl]amide

HRID 626677Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 626677
Cl[C:2]1[C:7]2=[CH:8][N:9]([C:11]3[C:16]([F:17])=[CH:15][CH:14]=[CH:13][C:12]=3[Cl:18])[N:10]=[C:6]2[CH:5]=[CH:4][N:3]=1.[CH:19]1([C:22]([NH2:24])=[O:23])[CH2:21][CH2:20]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]([F:17])[C:11]=1[N:9]1[CH:8]=[C:7]2[C:2]([NH:24][C:22]([CH:19]3[CH2:21][CH2:20]3)=[O:23])=[N:3][CH:4]=[CH:5][C:6]2=[N:10]1

Komponenten

7

Edukt 4

HCID 10796Cesium carbonateHCID 80376CyclopropanecarboxamideHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 866970434-Chloro-2-(2-chloro-6-fluorophenyl)-2H-pyrazolo[4,3-c]pyridine

Produkt 1

HCID 67701370Cyclopropanecarboxylic acid [2-(2-chloro-6-fluorophenyl)-2H-pyrazolo[4,3-c]pyridin-4-yl]amideAusbeute 43 %

Reagenzien, Katalysatoren, Lösungsmittel 2

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

Versuchsvorschrift

A mixture of 4-chloro-2-(2-chloro-6-fluorophenyl)-2H-pyrazolo[4,3-c]pyridine (76 mg, 0.27 mmol), cyclopropylcarboxamide (26 mg, 0.31 mmol), Pd2(dba)3 (7 mg, 0.007 mmol), Xantphos (16 mg, 0.027 mmol) and cesium carbonate (176 mg, 0.54 mmol) in dioxane (2 mL) was sealed in a microwave vial, purged with nitrogen, and irradiated at 150° C. for 20 minutes in the microwave. The reaction mixture was cooled and partitioned between ethyl acetate and water. The organic layer was washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (50% ethyl acetate in cyclohexane) to afford the title compound as a yellow solid (38 mg, 43% yield). 1H NMR (400 MHz, DMSO-d6): δ 11.15 (br s, 1H), 8.94 (s, 1H), 8.00 (d, J=6.3 Hz, 1H), 7.73 (td, J=8.3, 5.8 Hz, 1H), 7.67-7.66 (m, 1H), 7.64-7.52 (m, 2H), 7.36 (d, J=6.3 Hz, 1H), 2.18-2.12 (m, 1H), 0.93-0.86 (m, 4H). LCMS (Method B): RT=2.77 min, m/z: 331 [M+H+].

Aufarbeitung

  1. customwas sealed in a microwave vial
  2. custompurged with nitrogen
  3. customirradiated at 150° C. for 20 minutes in the microwave
  4. temperatureThe reaction mixture was cooled
  5. custompartitioned between ethyl acetate and water
  6. washThe organic layer was washed with brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel flash chromatography (50% ethyl acetate in cyclohexane)

Quellen und Nachweise

ORD-Eintrag
ord-fd77e9d93e904aa8beaffcae4f84962d
Quelldatensatz
uspto-grants-2016_04
Patentnummer
US09309240B2

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