Potassium Phosphate, Tribasic → Ethyl 6-cyclopropyl-8-[(2,6-difluorobenzyl)oxy]-2-methylimidazo[1,2-a]pyridine-3-carboxylate

HRID 1844151Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1844151
Br[C:2]1[CH:3]=[C:4]([O:17][CH2:18][C:19]2[C:24]([F:25])=[CH:23][CH:22]=[CH:21][C:20]=2[F:26])[C:5]2[N:6]([C:8]([C:12]([O:14][CH2:15][CH3:16])=[O:13])=[C:9]([CH3:11])[N:10]=2)[CH:7]=1.[CH:27]1(B(O)O)[CH2:29][CH2:28]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>[CH:27]1([C:2]2[CH:3]=[C:4]([O:17][CH2:18][C:19]3[C:24]([F:25])=[CH:23][CH:22]=[CH:21][C:20]=3[F:26])[C:5]3[N:6]([C:8]([C:12]([O:14][CH2:15][CH3:16])=[O:13])=[C:9]([CH3:11])[N:10]=3)[CH:7]=2)[CH2:29][CH2:28]1

Komponenten

7

Edukt 3

HCID 62657Potassium Phosphate, TribasicHCID 2760897Cyclopropylboronic acidHCID 86717880Ethyl 6-bromo-8-[(2,6-difluorobenzyl)oxy]-2-methylimidazo[1,2-a]pyridine-3-carboxylate

Produkt 1

HCID 86718174Ethyl 6-cyclopropyl-8-[(2,6-difluorobenzyl)oxy]-2-methylimidazo[1,2-a]pyridine-3-carboxylateAusbeute 103,7 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 75806TricyclohexylphosphineKatalysatorHCID 167845palladium(II) acetateKatalysatorHCID 22272177Toluene waterLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

500 mg of ethyl 6-bromo-8-[(2,6-difluorobenzyl)oxy]-2-methylimidazo[1,2-a]pyridine-3-carboxylate (Example 21A; 1.18 mmol; 1 equivalent), 131 mg of cyclopropaneboronic acid (1.53 mmol, 1.3 equivalents), 873 mg of potassium phosphate (4.12 mmol, 3.5 equivalents), 33 mg of tricyclohexylphosphine (0.12 mmol, 0.1 equivalents) and 13 mg of palladium(II) acetate (0.059 mmol, 5 mol %) were initially charged in 10.5 ml of toluene/water 20:1 and stirred at 80° C. for 16 h. The mixture was then filtered through silica gel and concentrated. The residue was chromatographed on a 50 g silica gel cartridge (Biotage Isolera, cyclohexane/ethyl acetate gradient as mobile phase). This gave 473 mg of a yellowish solid (98% pure, quantitative yield).

Aufarbeitung

  1. filtrationThe mixture was then filtered through silica gel
  2. concentrationconcentrated
  3. customThe residue was chromatographed on a 50 g silica gel cartridge (Biotage Isolera, cyclohexane/ethyl acetate gradient as mobile phase)

Quellen und Nachweise

ORD-Eintrag
ord-5648b0c71b3349d080faf011bb1565fb
Quelldatensatz
uspto-grants-2015_02
Patentnummer
US08946215B2

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