Potassium Carbonate → 6-(4-oxo-2-phenoxymethyl-6,7-dihydro-4H-pyrazolo[1,5-a]pyrazin-5-yl)-3',6'-dihydro-2'H-[2,4']bipyridinyl-1'-carboxylic acid tert-butyl ester

HRID 2046227Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2046227
Br[C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][N:11]3[N:14]=[C:15]([CH2:17][O:18][C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)[CH:16]=[C:10]3[C:9]2=[O:25])[CH:5]=[CH:4][CH:3]=1.B1([C:35]2[CH2:40][CH2:39][N:38]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:37][CH:36]=2)OC(C)(C)C(C)(C)O1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.CN(C=O)C.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:44]([O:43][C:41]([N:38]1[CH2:37][CH:36]=[C:35]([C:2]2[CH:3]=[CH:4][CH:5]=[C:6]([N:8]3[CH2:13][CH2:12][N:11]4[N:14]=[C:15]([CH2:17][O:18][C:19]5[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=5)[CH:16]=[C:10]4[C:9]3=[O:25])[N:7]=2)[CH2:40][CH2:39]1)=[O:42])([CH3:47])([CH3:45])[CH3:46]

Komponenten

8

Edukt 3

HCID 11430Potassium CarbonateHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 86670203HCID 86670203, Verbindung

Produkt 1

HCID 574100246-(4-oxo-2-phenoxymethyl-6,7-dihydro-4H-pyrazolo[1,5-a]pyrazin-5-yl)-3',6'-dihydro-2'H-[2,4']bipyridinyl-1'-carboxylic acid tert-butyl esterAusbeute 81,3 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
150 °C

Versuchsvorschrift

Tetrakis(triphenylphosphine)palladium(0) (7 mg, 0.006 mmol) was added to a stirred suspension of 5-(6-bromo-pyridin-2-yl)-2-phenoxymethyl-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one (50 mg, 0.125 mmol), (N-tert-butoxycarbonyl)-1,2,3,6-tetrahydropyridine-4-boronic acid pinacol ester (97 mg, 0.31 mmol) and potassium carbonate in a mixture of 1,4-dioxane (0.5 mL) and DMF (0.5 mL) in a sealed tube and under nitrogen. The mixture was stirred at 150° C. for 15 minutes under microwave irradiation. The mixture was diluted with water and extracted with AcOEt. The organic layer was separated, washed with brine, dried (MgSO4), filtered and the solvents evaporated in vacuo. The crude product was purified by flash column chromatography (silica; AcOEt in DCM 0/100 to 100/0). The desired fractions were collected and the solvents evaporated in vacuo to yield 6-(4-oxo-2-phenoxymethyl-6,7-dihydro-4H-pyrazolo[1,5-a]pyrazin-5-yl)-3′,6′-dihydro-2′H-[2,4′]bipyridinyl-1′-carboxylic acid tert-butyl ester (51 mg, 81%) as a pale yellow solid.

Aufarbeitung

  1. extractionextracted with AcOEt
  2. customThe organic layer was separated
  3. washwashed with brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customthe solvents evaporated in vacuo
  7. customThe crude product was purified by flash column chromatography (silica; AcOEt in DCM 0/100 to 100/0)
  8. customThe desired fractions were collected
  9. customthe solvents evaporated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-757944ce232a4f4ea8053ba3f3a77b44
Quelldatensatz
uspto-grants-2013_11
Patentnummer
US08592422B2

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