2-Methyltetrahydrofuran → Pf-04937319

HRID 1027708노트

반응식

HRID 1027708 반응식
[CH3:1][C:2]1[N:3]=[CH:4][C:5]([NH2:8])=[N:6][CH:7]=1.[Al](Cl)(C)C.[CH3:13][N:14]([CH3:39])[C:15]([C:17]1[N:22]=[CH: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](OCC)=[O:35])[CH:25]=2)=[CH:19][N:18]=1)=[O:16].CC1CCCO1>COC.O>[CH3:39][N:14]([CH3:13])[C:15]([C:17]1[N:22]=[CH: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

7

반응물 4

HCID 73012-MethyltetrahydrofuranHCID 79147ChlorodimethylaluminumHCID 3132155-Methylpyrazin-2-amineHCID 59483316Ethyl 4-(2-(dimethylcarbamoyl)pyrimidin-5-yloxy)-2-methylbenzofuran-6-carboxylate

생성물 1

HCID 46916694Pf-04937319

시약·촉매·용매 2

HCID 962Water용매HCID 8254Dimethyl Ether용매2회

실험 절차

To a solution of the 5-methyl-2-aminopyrazine (38.9 g, 356 mmol) in dimethylether (315 mL) in a 3-neck flask equipped with overhead stirring and a condensor at 0° C. was added Me2AlCl (1 M solution in hexanes) (715 mL). The mixture was warmed at room temperature and stirred for 1.5 hours. In a separate flask, ethyl 4-(2-(dimethylcarbamoyl)pyrimidin-5-yloxy)-2-methylbenzofuran-6-carboxylate (I-2a: 52.6 g, 142.5 mmol) was dissolved in dimethylether (210 mL). This mixture was then added to the complexed amine. A gum precipitated upon scratching the flask and dissipated into a solid. The resultant reaction was refluxed for 3.5 hours HPLC indicated 93% complete. Five liters of Rochelles salt made up in water and 2 liters of 2-methyltetrahydrofuran was added to the mixture. The reaction mixture was then poured into the biphasic system. The mixture was allowed to stir with overhead stirring for 14 hours, after which time, a yellow solid precipitated. The solid was collected through filteration. The solid retained was washed with 2-methyltetrahydrofuran. The resultant solid was dried in vacuo oven overnight to afford the title compound N,N-dimethyl-5-(2-methyl-6-((5-methylpyrazin-2-yl)carbamoyl)benzofuran-4-yloxy)pyrimidine-2-carboxamide (2): (49.98 g, 81%)

후처리

  1. stirringstirred for 1.5 hours
  2. customA gum precipitated
  3. customThe resultant reaction
  4. temperaturewas refluxed for 3.5 hours HPLC
  5. additionThe reaction mixture was then poured into the biphasic system
  6. stirringto stir with overhead
  7. stirringstirring for 14 hours
  8. customafter which time, a yellow solid precipitated
  9. customThe solid was collected through filteration
  10. washThe solid retained was washed with 2-methyltetrahydrofuran
  11. customThe resultant solid was dried in vacuo oven overnight

출처 및 근거

ORD 기록
ord-078264a94a1c47b0a85572ba465f13f4
출처 데이터셋
uspto-grants-2014_05
특허 번호
US08735396B2

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