5-Methylpyrazin-2-amine → N,N-dimethyl-5-(2-methyl-6-((5-methylpyrazin-2-yl)carbamoyl)benzofuran-4-yloxy)pyrazine-2-carboxamide

HRID 1027707노트

반응식

HRID 1027707 반응식
[CH3:1][C:2]1[N:3]=[CH:4][C:5]([NH2:8])=[N:6][CH:7]=1.[Cl-].C[Al+]C.[CH3:13][N:14]([CH3:39])[C:15]([C:17]1[N:18]=[CH:19][C:20]([O:23][C:24]2[C:29]3[CH:30]=[C:31]([CH3:33])[O:32][C:28]=3[CH:27]=[C:26]([C:34](OCC)=[O:35])[CH:25]=2)=[N:21][CH:22]=1)=[O:16]>COC>[CH3:39][N:14]([CH3:13])[C:15]([C:17]1[CH:22]=[N:21][C:20]([O:23][C:24]2[C:29]3[CH:30]=[C:31]([CH3:33])[O:32][C:28]=3[CH:27]=[C:26]([C:34](=[O:35])[NH:8][C:5]3[CH:4]=[N:3][C:2]([CH3:1])=[CH:7][N:6]=3)[CH:25]=2)=[CH:19][N:18]=1)=[O:16]

참가 물질

5

반응물 3

HCID 3132155-Methylpyrazin-2-amineHCID 16686359Dimethylalumanylium chlorideHCID 59483311Ethyl 4-(5-(dimethylcarbamoyl)pyrazin-2-yloxy)-2-methylbenzofuran-6-carboxylate

생성물 1

HCID 46916741N,N-dimethyl-5-(2-methyl-6-((5-methylpyrazin-2-yl)carbamoyl)benzofuran-4-yloxy)pyrazine-2-carboxamide수율 72%

시약·촉매·용매 1

HCID 8254Dimethyl Ether용매2회

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온도
0 °C

실험 절차

5-methyl-2-aminopyrazine (6.8 g, 63 mmol) was taken up in 70 mL of dimethylether and cooled to 0° C. Dimethyaluminium chloride (131 mmol, 1 M in hexane) was added dropwise. The resulting mixture was warmed up to ambient temperature and stirred for 30 min. Ethyl 4-(5-(dimethylcarbamoyl)pyrazin-2-yloxy)-2-methylbenzofuran-6-carboxylate (I-1d: 10.1 g, 27.3 mmol) in dimethylether (70 mL) was then added to the activated amine solution via canula. The combined solution was heated to reflux overnight. The reaction was cooled on ice and slowly quenched by the dropwise addition of aqueous Rochelle's salt (concentrated, 100 mL). The mixture was stirred for 20 minutes. The mixture was separated. Organic layer was washed with aqueous Rochelle's salt (30 ml), 1N HCl (30 ml), brine (30 ml), dried over sodium sulfate, and concentrated in vacuo. The crude product was purified by column chromatography (silica gel, gradient of ethyl acetate from 50-100% in heptane) to give desired N,N-dimethyl-5-(2-methyl-6-((5-methylpyrazin-2-yl)carbamoyl)benzofuran-4-yloxy)pyrazine-2-carboxamide (1: 8.5 gram 72%).

후처리

  1. temperatureThe resulting mixture was warmed up to ambient temperature
  2. temperatureThe combined solution was heated
  3. temperatureto reflux overnight
  4. temperatureThe reaction was cooled on ice
  5. customslowly quenched by the dropwise addition of aqueous Rochelle's salt (concentrated, 100 mL)
  6. stirringThe mixture was stirred for 20 minutes
  7. customThe mixture was separated
  8. washOrganic layer was washed with aqueous Rochelle's salt (30 ml), 1N HCl (30 ml), brine (30 ml)
  9. dry with materialdried over sodium sulfate
  10. concentrationconcentrated in vacuo
  11. customThe crude product was purified by column chromatography (silica gel, gradient of ethyl acetate from 50-100% in heptane)

출처 및 근거

ORD 기록
ord-95d1c7ae385a4911b54d65aa54590f53
출처 데이터셋
uspto-grants-2014_05
특허 번호
US08735396B2

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