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 1749669ノート

反応式

HRID 1749669 の反応式
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

参加物

6

反応物 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

生成物 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-carboxylate収率 79.3%

試薬・触媒・溶媒 2

HCID 6102075Dichlorobis(triphenylphosphine)palladium触媒HCID 79104-Methyl-2-Pentanol溶媒

反応条件

温度
140 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-7e8fee3d929447498a1ad701a1dfd5ab
出典データセット
uspto-grants-2015_10
特許番号
US09156831B2

反応ノート

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