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 1749669노트

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HRID 1749669 반응식
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

참가 물질

6

반응물 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

생성물 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-carboxylate수율 79.3%

시약·촉매·용매 2

HCID 6102075Dichlorobis(triphenylphosphine)palladium촉매HCID 79104-Methyl-2-Pentanol용매

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온도
140 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-7e8fee3d929447498a1ad701a1dfd5ab
출처 데이터셋
uspto-grants-2015_10
특허 번호
US09156831B2

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