Methanesulfonyl chloride → 6-bromo-N-(5-(5-((3-cyanoazetidin-1-yl)methyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide

HRID 1045458Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1045458
[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:11]([NH:13][C:14]3[CH:19]=[C:18]([C:20]4[N:24]=[C:23]([CH2:25]O)[O:22][N:21]=4)[CH:17]=[CH:16][C:15]=3[CH3:27])=[O:12])=[CH:9][N:10]=2)[CH:7]=1.CCN(C(C)C)C(C)C.CS(Cl)(=O)=O.[NH:42]1[CH2:45][CH:44]([C:46]#[N:47])[CH2:43]1>ClCCl.CN(C=O)C.O>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:11]([NH:13][C:14]3[CH:19]=[C:18]([C:20]4[N:24]=[C:23]([CH2:25][N:42]5[CH2:45][CH:44]([C:46]#[N:47])[CH2:43]5)[O:22][N:21]=4)[CH:17]=[CH:16][C:15]=3[CH3:27])=[O:12])=[CH:9][N:10]=2)[CH:7]=1

Komponenten

8

Edukt 4

HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 221323843-AzetidinecarbonitrileHCID 712806916-bromo-N-(5-(5-(hydroxymethyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide

Produkt 1

HCID 712807916-bromo-N-(5-(5-((3-cyanoazetidin-1-yl)methyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

To a solution of 6-bromo-N-(5-(5-(hydroxymethyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide (142) (200 mg, 0.47 mmol) and DIEA (0.25 mL, 1.41 mmol) in dichloromethane (5 mL) was added MsCl (108.1 mg, 0.94 mmol). The mixture was stirred at room temperature for 10 minutes and then diluted with dichloromethane (10 mL) and washed with water. The organic layers were dried over Na2SO4, filtered and concentrated to give a residue which was dissolved in DMF (2 mL). Then azetidine-3-carbonitrile (116 mg, 1.41 mmol) was added and the reaction mixture was heated at 80° C. for 1 hour. The reaction mixture was diluted with water (50 mL) and extracted with EtOAc. The organic layers were dried over Na2SO4, filtered and concentrated to give the crude product which was purified by silica chromatography to yield 6-bromo-N-(5-(5-((3-cyanoazetidin-1-ylmethyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide (143). 1H NMR (400 MHz, d6-DMSO) δ 10.15 (s, 1H), 9.62 (dd, J=0.8, 2.0 Hz, 1H), 8.60 (s, 1H), 8.07 (d, J=1.6 Hz, 1H), 7.83 (dd, J=1.6, 8.0 Hz, 1H), 7.79 (dd, J=0.8, 9.6 Hz, 1H), 7.68 (dd, J=2.0, 9.6 Hz, 1H), 7.51 (d, J=8.4 Hz, 1H), 4.06 (s, 2H), 3.67 (m, 2H), 3.51-3.60 (m, 3H), 2.37 (s, 3H). MS m/z 492.0, 494.0 (M+1)+.

Aufarbeitung

  1. washwashed with water
  2. dry with materialThe organic layers were dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto give a residue which
  6. temperaturethe reaction mixture was heated at 80° C. for 1 hour
  7. extractionextracted with EtOAc
  8. dry with materialThe organic layers were dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto give the crude product which
  12. customwas purified by silica chromatography

Quellen und Nachweise

ORD-Eintrag
ord-98d93cc515d549d7b07532264e5c594e
Quelldatensatz
uspto-grants-2013_10
Patentnummer
US08569283B2

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