Pyridine → 3-(5-((4-(1-(4-(2,3-Dimethylphenoxy)butanoyl)-1,2,3,4-tetrahydroquinolin-5-yl)-1H-pyrazol-1-yl)methyl)-1H-tetrazol-1-yl)propanenitrile

HRID 2175275Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2175275
[C:1]([CH2:3][CH2:4][NH:5][C:6](=O)[CH2:7][N:8]1[CH:12]=[C:11]([C:13]2[CH:22]=[CH:21][CH:20]=[C:19]3[C:14]=2[CH2:15][CH2:16][CH2:17][N:18]3[C:23](=[O:36])[CH2:24][CH2:25][CH2:26][O:27][C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([CH3:34])[C:29]=2[CH3:35])[CH:10]=[N:9]1)#[N:2].N1C=CC=CC=1.P(Cl)(Cl)(Cl)(Cl)Cl.C[Si]([N:54]=[N+:55]=[N-:56])(C)C>C(Cl)Cl>[CH3:35][C:29]1[C:30]([CH3:34])=[CH:31][CH:32]=[CH:33][C:28]=1[O:27][CH2:26][CH2:25][CH2:24][C:23]([N:18]1[C:19]2[C:14](=[C:13]([C:11]3[CH:10]=[N:9][N:8]([CH2:7][C:6]4[N:5]([CH2:4][CH2:3][C:1]#[N:2])[N:56]=[N:55][N:54]=4)[CH:12]=3)[CH:22]=[CH:21][CH:20]=2)[CH2:15][CH2:16][CH2:17]1)=[O:36]

Komponenten

6

Edukt 4

HCID 1049PyridineHCID 24819Phosphorus pentachlorideHCID 78378AzidotrimethylsilaneHCID 70983502N-(2-cyanoethyl)-2-(4-(1-(4-(2,3-dimethylphenoxy)butanoyl)-1,2,3,4-tetrahydroquinolin-5-yl)-1H-pyrazol-1-yl)acetamide

Produkt 1

HCID 709827333-(5-((4-(1-(4-(2,3-Dimethylphenoxy)butanoyl)-1,2,3,4-tetrahydroquinolin-5-yl)-1H-pyrazol-1-yl)methyl)-1H-tetrazol-1-yl)propanenitrileAusbeute 81 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a solution of N-(2-cyanoethyl)-2-(4-(1-(4-(2,3-dimethylphenoxy)butanoyl)-1,2,3,4-tetrahydroquinolin-5-yl)-1H-pyrazol-1-yl)acetamide (20 mg, 0.04 mmol) and pyridine (19 μL, 0.24 mmol) in DCM (0.4 mL) under argon was added PCl5 (13 mg, 0.06 mmol) in one portion, and the resulting mixture was heated to reflux for 3 h. The reaction was cooled to room temperature and trimethylsilyl azide (18 mg, 0.16 mmol) was added. The resulting mixture was stirred at room temperature overnight and carefully quenched with saturated aqueous NaHCO3. The resulting mixture was stirred vigorously for 15 min. The organic phase was separated, dried over anhydrous Na2SO4, filtered, and concentrated. The resulting residue was purified by flash chromatography (0-100% ethyl acetate:hexanes) to afford the title compound (17 mg, 81% yield) as white foam. LCMS, [M+H]+=525.2. 1H NMR (400 MHz, CDCl3) δ 7.54 (s, 1H), 7.47 (s, 1H), 7.30-7.16 (m, 2H), 7.10 (d, J=8.7 Hz, 1H), 7.03 (t, J=7.9 Hz, 1H), 6.76 (d, J=7.5 Hz, 1H), 6.64 (d, J=8.2 Hz, 1H), 5.74 (s, 2H), 4.95 (t, J=6.9 Hz, 2H), 3.93 (s, 2H), 3.78 (t, J=6.8 Hz, 2H), 3.06 (t, J=6.9 Hz, 2H), 2.74 (t, J=7.1 Hz, 2H), 2.52 (s, 2H), 2.24-2.11 (m, 5H), 1.96-1.78 (m, 5H).

Aufarbeitung

  1. temperaturethe resulting mixture was heated
  2. temperatureto reflux for 3 h
  3. customcarefully quenched with saturated aqueous NaHCO3
  4. stirringThe resulting mixture was stirred vigorously for 15 min
  5. customThe organic phase was separated
  6. dry with materialdried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe resulting residue was purified by flash chromatography (0-100% ethyl acetate:hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-7b71fa9cc3f2427b8873f0999c3edd4d
Quelldatensatz
uspto-grants-2015_06
Patentnummer
US09062028B2

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