Diisopropylamine → 6-(5-methoxy-1-methyl-1H-indol-3-yl)-5H-pyrrolo[2,3-b]pyrazine

HRID 548998

反応式

HRID 548998 の反応式
C(NC(C)C)(C)C.C([Li])CCC.[CH3:13][C:14]1[CH:19]=[N:18][CH:17]=[CH:16][N:15]=1.[CH3:20][O:21][C:22]1[CH:23]=[C:24]2[C:28](=[CH:29][CH:30]=1)[N:27]([CH3:31])[CH:26]=[C:25]2[C:32]#[N:33]>O1CCCC1.O>[CH3:20][O:21][C:22]1[CH:23]=[C:24]2[C:28](=[CH:29][CH:30]=1)[N:27]([CH3:31])[CH:26]=[C:25]2[C:32]1[NH:33][C:19]2=[N:18][CH:17]=[CH:16][N:15]=[C:14]2[CH:13]=1

参加物

7

反応物 4

HCID 7912DiisopropylamineHCID 79762-MethylpyrazineHCID 224772695-methoxy-1-methyl-1H-indole-3-carbonitrileHCID 178418339Butyllithium

生成物 1

HCID 98604486-(5-methoxy-1-methyl-1H-indol-3-yl)-5H-pyrrolo[2,3-b]pyrazine収率 24.5%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒2 回

実験手順

A stirred solution of diisopropylamine (59.9 mL) in tetrahydrofuran (1400 mL), at −15° C. and under nitrogen, was treated with a solution of n-butyllithium in hexanes (131 mL, 1.6M) over 25 minutes, whilst maintaining the temperature below −10° C. After stirring for 30 minutes the mixture was treated with methylpyrazine (26.8 g) over 15 minutes, then stirred for 1 hour and then treated with a solution of 5-methoxy-1-methyl-1H-indole-3-carbonitrile [53 g, Reference Example 1(a)] in tetrahydrofuran (600 mL) over 1 hour, keeping the temperature below −10° C. The reaction mixture was allowed to warm to room temperature over 2 hours, then stood overnight and then treated with water (100 mL). The tetrahydrofuran was removed in vacuo and the resultant mixture was partitioned between ethyl acetate (500 mL) and water (200 mL). The two layers were separated, and the aqueous layer was extracted with ethyl acetate (200 mL). The combined organics were washed with water (500 mL) then evaporated. The residue was subjected to flash chromatography on silica eluting with a mixture of dichloromethane and methanol (19:1, v/v) to give the title compound (19.4 g) as a grey solid, m.p. 270-272° C. MS: 279 (MH+).

後処理

  1. temperaturewhilst maintaining the temperature below −10° C
  2. stirringstirred for 1 hour
  3. customthe temperature below −10° C
  4. waitstood overnight
  5. customThe tetrahydrofuran was removed in vacuo
  6. customthe resultant mixture was partitioned between ethyl acetate (500 mL) and water (200 mL)
  7. customThe two layers were separated
  8. extractionthe aqueous layer was extracted with ethyl acetate (200 mL)
  9. washThe combined organics were washed with water (500 mL)
  10. customthen evaporated
  11. additionThe residue was subjected to flash chromatography on silica eluting with a mixture of dichloromethane and methanol (19:1

出典と根拠

ORDレコード
ord-5636d79c3c4746eabfb480729c68edad
出典データセット
uspto-grants-2011_05
特許番号
US07943616B2

関連ノート

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