Lithium Chloride → tert-butyl 4-(5-(5-amino-6-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazin-2-yl)-1-methyl-1H-1,2,4-triazol-3-yl)piperidine-1-carboxylate

HRID 1749669Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1749669
Br[C:2]1[N:6]([CH3:7])[N:5]=[C:4]([CH:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)[N:3]=1.[C:21]([C:25]1[O:29][C:28]([C:30]2[C:31]([NH2:40])=[N:32][CH:33]=[C:34]([Sn](C)(C)C)[N:35]=2)=[N:27][N:26]=1)([CH3:24])([CH3:23])[CH3:22].[Cl-].[Li+]>CC(C)CC(O)C.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[NH2:40][C:31]1[N:32]=[CH:33][C:34]([C:2]2[N:6]([CH3:7])[N:5]=[C:4]([CH:8]3[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]3)[N:3]=2)=[N:35][C:30]=1[C:28]1[O:29][C:25]([C:21]([CH3:24])([CH3:23])[CH3:22])=[N:26][N:27]=1

Komponenten

6

Edukt 3

HCID 433294Lithium ChlorideHCID 86727653tert-butyl 4-(5-bromo-1-methyl-1H-1,2,4-triazol-3-yl)piperidine-1-carboxylateHCID 867276563-(5-Tert-butyl-1,3,4-oxadiazol-2-yl)-5-(trimethylstannyl)pyrazin-2-amine

Produkt 1

HCID 86727657tert-butyl 4-(5-(5-amino-6-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazin-2-yl)-1-methyl-1H-1,2,4-triazol-3-yl)piperidine-1-carboxylateAusbeute 79,3 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6102075Dichlorobis(triphenylphosphine)palladiumKatalysatorHCID 79104-Methyl-2-PentanolLösungsmittel

Reaktionsbedingungen

Temperatur
140 °C

Versuchsvorschrift

To a stirred suspension of tert-butyl 4-(5-bromo-1-methyl-1H-1,2,4-triazol-3-yl)piperidine-1-carboxylate (2700 mg, 7.82 mmol) and 3-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-(trimethylstannyl)pyrazin-2-amine (2988 mg, 7.82 mmol) in 4-methyl-2-pentanol (28 mL) were added lithium chloride (995 mg, 23.46 mmol) and bis(triphenylphosphine) palladium (II) chloride (220 mg, 0.31 mmol). The mixture was degassed with argon and heated at 140° C. for 2 h. The reaction was cooled down and the resulting precipitate was collected by filtration, washed with isopropanol (25 mL), water (25 mL) and dried under suction. The isopropanol organic fraction was concentrated and the precipitate formed was collected and combined with the main precipitate affording tert-butyl 4-(5-(5-amino-6-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazin-2-yl)-1-methyl-1H-1,2,4-triazol-3-yl)piperidine-1-carboxylate (3.0 g, 79%): 1H NMR Spectrum: (DMSO-d6) 1.41 (9H, s), 1.45 (9H, s), 1.50-1.68 (2H, m), 1.95 (3H, dd), 2.78-3.05 (1H, m), 3.96 (3H, d), 4.21 (3H, s), 8.86 (1H, s); Mass Spectrum [M+H]+=484.

Aufarbeitung

  1. customThe mixture was degassed with argon
  2. temperatureThe reaction was cooled down
  3. filtrationthe resulting precipitate was collected by filtration
  4. washwashed with isopropanol (25 mL), water (25 mL)
  5. customdried under suction
  6. concentrationThe isopropanol organic fraction was concentrated
  7. customthe precipitate formed
  8. customwas collected

Quellen und Nachweise

ORD-Eintrag
ord-7e8fee3d929447498a1ad701a1dfd5ab
Quelldatensatz
uspto-grants-2015_10
Patentnummer
US09156831B2

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