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Cesium carbonate → Methyl 5-{3-(cyanomethyl)-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]azetidin-1-yl}pyrazine-2-carboxylate

HRID 2363357
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 2363357
Cl.[CH3:2][C:3]1([CH3:22])[C:7]([CH3:9])([CH3:8])[O:6][B:5]([C:10]2[CH:11]=[N:12][N:13]([C:15]3([CH2:19][C:20]#[N:21])[CH2:18][NH:17][CH2:16]3)[CH:14]=2)[O:4]1.Cl[C:24]1[N:25]=[CH:26][C:27]([C:30]([O:32][CH3:33])=[O:31])=[N:28][CH:29]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:20]([CH2:19][C:15]1([N:13]2[CH:14]=[C:10]([B:5]3[O:6][C:7]([CH3:8])([CH3:9])[C:3]([CH3:22])([CH3:2])[O:4]3)[CH:11]=[N:12]2)[CH2:16][N:17]([C:24]2[N:25]=[CH:26][C:27]([C:30]([O:32][CH3:33])=[O:31])=[N:28][CH:29]=2)[CH2:18]1)#[N:21]
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

7

Edukt 4

HCID 10796Cesium carbonateHCID 406081Methyl 5-chloropyrazine-2-carboxylateHCID 634876Binap, (A+-)-HCID 712080171416785-40-4Freebase

Produkt 1

HCID 71143602Methyl 5-{3-(cyanomethyl)-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]azetidin-1-yl}pyrazine-2-carboxylateAusbeute 53,7 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 167845palladium(II) acetateKatalysatorHCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A mixture of {3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile HCl salt (400. mg, 1.23 mmol), methyl 5-chloropyrazine-2-carboxylate (223 mg, 1.29 mmol), cesium carbonate (800 mg, 2.5 mmol), palladium acetate (28 mg, 0.12 mmol) and (S)-(−)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (150 mg, 0.25 mmol) in toluene (5 mL) was stirred at 100° C. for 3 h. After the reaction mixture was cooled to room temperature, the solid was separated, and washed with ethyl acetate twice. The filtrate was concentrated under reduced pressure. The residue was purified by flash chromatography on a silica gel column with methanol in methylene chloride (0-5%) to afford the desired product (0.28 g). LCMS (M+H)+: 425.2.

Aufarbeitung

  1. temperatureAfter the reaction mixture was cooled to room temperature
  2. customthe solid was separated
  3. washwashed with ethyl acetate twice
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. customThe residue was purified by flash chromatography on a silica gel column with methanol in methylene chloride (0-5%)

Quellen und Nachweise

ORD-Eintrag
ord-a85a6ebaa7db423ea2d46449b322407b
Quelldatensatz
uspto-grants-2014_04
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08691807B2

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