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

HRID 1765560

반응식

HRID 1765560 반응식
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

참가 물질

7

반응물 4

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

생성물 1

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

시약·촉매·용매 2

HCID 962Water용매HCID 8028Tetrahydrofuran용매2회

실험 절차

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 [53g, 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, 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 (20 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+).

후처리

  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 (20 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

출처 및 근거

ORD 기록
ord-48c3c58fb33740de90fa88fd1b3b0c23
출처 데이터셋
uspto-grants-2007_06
특허 번호
US07227020B2

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