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 1749669Notes

Reaction equation

HRID 1749669 reaction equation
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

Participants

6

Reactant 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

Product 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-carboxylateYield 79.3%

Reagents, catalysts & solvents 2

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 79104-Methyl-2-PentanolSolvent

Conditions

Temperature
140 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-7e8fee3d929447498a1ad701a1dfd5ab
Source dataset
uspto-grants-2015_10
Patent number
US09156831B2

Reaction notes

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