N-(2-methyl-5-(5-(3-oxocyclobutyl)-1,2,4-oxadiazol-3-yl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide → N-(5-(5-(3-cyclopropyl-3-hydroxycyclobutyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide

HRID 1497916

Reaktionsgleichung

Reaktionsgleichung von HRID 1497916
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]=[C:11]([CH:13]3[CH2:16][C:15](=[O:17])[CH2:14]3)[O:10][N:9]=2)=[CH:4][C:3]=1[NH:18][C:19]([C:21]1[N:25]2[CH:26]=[CH:27][CH:28]=[CH:29][C:24]2=[N:23][CH:22]=1)=[O:20].[CH:30]1([Mg]Br)[CH2:32][CH2:31]1>C1COCC1>[CH:30]1([C:15]2([OH:17])[CH2:16][CH:13]([C:11]3[O:10][N:9]=[C:8]([C:5]4[CH:6]=[CH:7][C:2]([CH3:1])=[C:3]([NH:18][C:19]([C:21]5[N:25]6[CH:26]=[CH:27][CH:28]=[CH:29][C:24]6=[N:23][CH:22]=5)=[O:20])[CH:4]=4)[N:12]=3)[CH2:14]2)[CH2:32][CH2:31]1

Komponenten

4

Edukt 2

HCID 71280448N-(2-methyl-5-(5-(3-oxocyclobutyl)-1,2,4-oxadiazol-3-yl)phenyl)imidazo[1,2-a]pyridine-3-carboxamideHCID 178418630HCID 178418630, Verbindung

Produkt 1

HCID 71280497N-(5-(5-(3-cyclopropyl-3-hydroxycyclobutyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a stirring solution of N-(2-methyl-5-(5-(3-oxocyclobutyl)-1,2,4-oxadiazol-3-yl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide (10) (250 mg, 0.645 mmol) in anhydrous THF (10 mL) at −78° C. under Argon was added cyclopropylmagnesium bromide (2.6 mL, 1.3 mmol). The reaction was stirred for 30 minutes at room temperature and quenched with 1N HCl at 0° C. The crude product was extracted with ethylacetate. The organic layer was washed with saturated ammonium chloride, water and dried over anhydrous sodium sulfate. The crude product was purified by silica chromatography to give N-(5-(5-(3-cyclopropyl-3-hydroxycyclobutyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide (F31). 1H NMR (400 MHz, d6-DMSO) δ 10.04 (s, 1H), 9.47-9.45 (m, 1H), 8.59 (s, 1H), 8.07 (d, J=1.6 Hz, 1H), 7.83-7.76 (m, 2H), 7.55-7.52 (m, 1H), 7.49 (d, J=8.0 Hz, 1H), 7.20-7.16 (m, 1H), 5.19 (s, 1H), 4.37-4.35 (m, 1H), 3.46-3.40 (m, 1H), 2.45-2.40 (m, 2H), 2.36 (s, 3H), 1.54-1.41 (m, 2H), 1.19-1.14 (m, 1H), 0.34-0.26 (m, 2H), 0.22-0.11 (m, 1H). MS m/z 430.47 (M+1)+.

Aufarbeitung

  1. customquenched with 1N HCl at 0° C
  2. extractionThe crude product was extracted with ethylacetate
  3. washThe organic layer was washed with saturated ammonium chloride, water
  4. dry with materialdried over anhydrous sodium sulfate
  5. customThe crude product was purified by silica chromatography

Quellen und Nachweise

ORD-Eintrag
ord-4db6ada5fc5146af883ee5f86192b59d
Quelldatensatz
uspto-grants-2015_12
Patentnummer
US09199981B2

Verknüpfte Notizen

Wird geladen…