Water → 5-Imidazo[1,2-a]pyridin-7-yl-pyridine-2-carboxylic acid methyl ester

HRID 341222

Reaktionsgleichung

Reaktionsgleichung von HRID 341222
CC1(C)C(C)(C)OB([C:9]2[CH:14]=[CH:13][N:12]3[CH:15]=[CH:16][N:17]=[C:11]3[CH:10]=2)O1.[CH3:19][O:20][C:21]([C:23]1[CH:28]=[CH:27][C:26](Br)=[CH:25][N:24]=1)=[O:22].C(=O)([O-])[O-].[Cs+].[Cs+].O>COCCOC.CS(C)=O>[CH3:19][O:20][C:21]([C:23]1[CH:28]=[CH:27][C:26]([C:9]2[CH:14]=[CH:13][N:12]3[CH:15]=[CH:16][N:17]=[C:11]3[CH:10]=2)=[CH:25][N:24]=1)=[O:22]

Komponenten

7

Edukt 4

HCID 962WaterHCID 10796Cesium carbonateHCID 7016458Methyl 5-bromopyridine-2-carboxylateHCID 49758473Imidazo[1,2-a]pyridin-7-ylboronic acid pinacol ester

Produkt 1

HCID 593207795-Imidazo[1,2-a]pyridin-7-yl-pyridine-2-carboxylic acid methyl ester

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 679Dimethyl SulfoxideLösungsmittelHCID 80711,2-DimethoxyethaneLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

To a stirred mixture of 7-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-imidazo[1,2-a]pyridine (732 mg, 3 mmol), 5-bromopyridine-2-carboxylic acid methyl ester (650 mg, 3 mmol) and cesium carbonate (2.0 g, 6 mmol) in dry DME (15 ml) was added PdCl2dppf (220 mg, 0.3 mmol) and H2O (55 μl, 3 mmol). The reaction mixture was deoxygenated and then heated at 80° C. for 3 h. The mixture was allowed to cool, then partitioned between CH2Cl2/H2O and stirred for 20 min. The solid material was filtered off and washed with MeOH (100 ml). The CH2Cl2 layer was separated, combined with the MeOH washings and the solvent removed in vacuo. The residue was purified by silica column chromatography (0-3% 2M NH3. MeOH/CH2Cl2) to afford a dark yellow solid, which was used directly in the next reaction (492 mg). MS: [M+H]+=254. 1H NMR d6 DMSO: 9.21 (1H, d), 8.71 (1H, d), 8.44 (1H, dd), 8.20-8.10 (2H, m), 8.04 (1H, s), 7.69 (1H, s), 7.43 (1H, dd), 3.92 (3H, s).

Aufarbeitung

  1. customThe reaction mixture was deoxygenated
  2. temperatureto cool
  3. custompartitioned between CH2Cl2/H2O
  4. filtrationThe solid material was filtered off
  5. washwashed with MeOH (100 ml)
  6. customThe CH2Cl2 layer was separated
  7. customthe solvent removed in vacuo
  8. customThe residue was purified by silica column chromatography (0-3% 2M NH3. MeOH/CH2Cl2)
  9. customto afford a dark yellow solid, which
  10. customwas used directly in the next reaction (492 mg)

Quellen und Nachweise

ORD-Eintrag
ord-a6dc61c2ac2d47379f6a0a06453a8870
Quelldatensatz
uspto-grants-2014_11
Patentnummer
US08895745B2

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