Acetoxyacetic acid → 6-bromo-N-(5-(5-(hydroxymethyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide

HRID 570350

Reaktionsgleichung

Reaktionsgleichung von HRID 570350
C(C1NC=CN=1)(C1NC=CN=1)=O.C([O:16][CH2:17][C:18]([OH:20])=O)(=O)C.[Br:21][C:22]1[CH:23]=[CH:24][C:25]2[N:26]([C:28]([C:31]([NH:33][C:34]3[CH:39]=[C:38]([C:40](=[NH:43])[NH:41]O)[CH:37]=[CH:36][C:35]=3[CH3:44])=[O:32])=[CH:29][N:30]=2)[CH:27]=1.O.[OH-].[Li+]>CN1C(=O)CCC1.C1COCC1.CO.O>[Br:21][C:22]1[CH:23]=[CH:24][C:25]2[N:26]([C:28]([C:31]([NH:33][C:34]3[CH:39]=[C:38]([C:40]4[N:41]=[C:18]([CH2:17][OH:16])[O:20][N:43]=4)[CH:37]=[CH:36][C:35]=3[CH3:44])=[O:32])=[CH:29][N:30]=2)[CH:27]=1

Komponenten

7

Edukt 4

HCID 83766Acetoxyacetic acidHCID 168937Lithium hydroxide, monohydrateHCID 5250894Bis-(1H-imidazol-2-YL)-methanoneHCID 178425643HCID 178425643, Verbindung

Produkt 1

HCID 712806916-bromo-N-(5-(5-(hydroxymethyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 13387N-methyl-2-pyrrolidoneLösungsmittelHCID 21892291Methanol tetrahydrofuran waterLösungsmittel

Reaktionsbedingungen

Temperatur
125 °C

Versuchsvorschrift

Carbonyl diimidazole (CDI) (2.3 g, 14.24 mmol) was added to a stirred solution of 2-acetoxyacetic acid (1.68 g, 14.24 mmol) in NMP (10 mL). After 30 minutes, 6-bromo-N-(5-(N-hydroxycarbamimidoyl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide (50f) (1.38 g, 3.56 mmol) was added in one portion and the resulting solution was stirred for 30 minutes before it was heated at 125° C. for 15 minutes in a microwave reactor. The reaction solution was subjected to standard aqueous work up to afford a residue which was hydrolyzed by lithium hydroxide monohydrate (897 mg, 21.36 mmol) in THF/MeOH/H2O (3:2:1). After removal of all solvents 2M NaHCO3 (10 mL) was added. The precipitate was filtered and dried in air to afford 6-bromo-N-(5-(5-(hydroxymethyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide (142). 1H NMR (400 MHz, d6-DMSO) δ 10.14 (s, 1H), 9.64 (d, J=1.2 Hz, 1H), 8.60 (s, 1H), 8.11 (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), 7.67 (dd, J=2.0, 9.6 Hz, 1H), 7.51 (d, J=8.0 Hz, 1H), 6.09 (s, 1H), 4.81 (s, 2H), 2.37 (s, 3H). MS m/z 427.9, 429.9 (M+1)+.

Aufarbeitung

  1. customto afford a residue which
  2. customAfter removal of all solvents 2M NaHCO3 (10 mL)
  3. additionwas added
  4. filtrationThe precipitate was filtered
  5. customdried in air

Quellen und Nachweise

ORD-Eintrag
ord-da3a47ce281a42b0a244d9cec2d22196
Quelldatensatz
uspto-grants-2015_05
Patentnummer
US09023839B2

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