Ammonium Chloride → 2-(2-Methylphenyl)-5-[(5-methylpyridin-2-yl)methyl]-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one

HRID 341102Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 341102
Br[C:2]1[CH:3]=[CH:4][C:5]([CH2:8][N:9]2[C:18]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[C:12]3=[N:19][N:20]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=4[CH3:29])[C:21](=[O:22])[C:11]3=[CH:10]2)=[N:6][CH:7]=1.[CH3:30][Zn]C.[Cl-].[NH4+]>O1CCCC1.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:29][C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=1[N:20]1[C:21](=[O:22])[C:11]2=[CH:10][N:9]([CH2:8][C:5]3[CH:4]=[CH:3][C:2]([CH3:30])=[CH:7][N:6]=3)[C:18]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[C:12]2=[N:19]1

Komponenten

6

Edukt 3

HCID 25517Ammonium ChlorideHCID 681541675-[(5-bromopyridin-2-yl)methyl]-2-(2-methylphenyl)-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-oneHCID 178477796HCID 178477796, Verbindung2×

Produkt 1

HCID 681542252-(2-Methylphenyl)-5-[(5-methylpyridin-2-yl)methyl]-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumKatalysator2×HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
70 °C

Versuchsvorschrift

5-[(5-Bromopyridin-2-yl)methyl]-2-(2-methylphenyl)-2,5-dihydro-3/1-pyrazolo[4,3-c]quinolin-3-one (Example 743, 40 mg, 0.090 mmol) was dissolved in tetrahydrofuran (2 mL), and the mixture was sparged under an atmosphere of nitrogen. Dimethyl zinc (0.49 mL, 2.0 Min toluene, 0.90 mmol, 10 equiv) and tetrakis(triphenylphosphine) palladium (0) (1.0 mg, 0.01 mmol, 0.1 equiv) were added and the mixture was placed into an oil bath preheated to 60° C. for 4 hours. Additional dimethyl zinc (0.49 mL, 2.0 M in toluene, 0.90 mmol, 10 equiv) and tetrakis(triphenylphosphine) palladium (0) (1.0 mg, 0.01 mmol, 0.1 equiv) were added and the mixture was heated at 70° C. for an additional 3 hours. The mixture was cooled to ambient temperature, treated with ammonium chloride (0.2 mL, aqueous saturated), and concentrated in vacuo. The residue was purified by preparative reverse phase HPLC (90:10 to 5:95; water containing 0.1% trifluoroacetic acid:acetonitrile containing 0.1% trifluoroacetic acid), providing the titled compound: 1H-NMR (400 MHz, CD3OD) δ 8.98 (1H, s), 8.39 (1H, s), 8.35-8.32 (1H, m), 7.78 (1H, d, J=8.5 Hz), 7.73 (1H, d, J=6.2 Hz), 7.66-7.56 (2H, m), 7.42-7.35 (5H, m), 5.86 (2H, s), 234 (3H, s), 2.28 (3H, s), ppm; low resolution mass spectrometry (ES+) m/z 381.0 (M+H)+; calculated for C24H20N4O: 381.2].

Aufarbeitung

  1. customthe mixture was sparged under an atmosphere of nitrogen
  2. customthe mixture was placed into an oil bath
  3. temperatureThe mixture was cooled to ambient temperature
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by preparative reverse phase HPLC (90:10 to 5:95; water containing 0.1% trifluoroacetic acid:acetonitrile containing 0.1% trifluoroacetic acid)

Quellen und Nachweise

ORD-Eintrag
ord-2c24075cf180464898ae28680231e27a
Quelldatensatz
uspto-grants-2014_11
Patentnummer
US08895580B2

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