Dimethylformamide → 5-chloro-2-(1-methyl-1H-pyrazol-4-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridine-4-carbonitrile

HRID 2362737노트

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HRID 2362737 반응식
Cl[C:2]1[C:7]([Cl:8])=[CH:6][N:5]=[C:4]2[N:9]([S:18]([C:21]3[CH:27]=[CH:26][C:24]([CH3:25])=[CH:23][CH:22]=3)(=[O:20])=[O:19])[C:10]([C:12]3[CH:13]=[N:14][N:15]([CH3:17])[CH:16]=3)=[CH:11][C:3]=12.[CH3:28][N:29](C)C=O>O.C(OCC)(=O)C.[C-]#N.[Zn+2].[C-]#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:8][C:7]1[CH:6]=[N:5][C:4]2[N:9]([S:18]([C:21]3[CH:22]=[CH:23][C:24]([CH3:25])=[CH:26][CH:27]=3)(=[O:20])=[O:19])[C:10]([C:12]3[CH:13]=[N:14][N:15]([CH3:17])[CH:16]=3)=[CH:11][C:3]=2[C:2]=1[C:28]#[N:29]

참가 물질

7

반응물 2

HCID 6228DimethylformamideHCID 670029234,5-dichloro-2-(1-methyl-1H-pyrazol-4-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridine

생성물 1

HCID 670035475-chloro-2-(1-methyl-1H-pyrazol-4-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridine-4-carbonitrile

시약·촉매·용매 4

HCID 11186Zinc cyanide (Zn(CN)2)촉매2회HCID 178418397HCID 178418397, 화합물촉매2회HCID 962Water용매HCID 8857Ethyl Acetate용매

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온도
160 °C

실험 절차

A solution in a microwave vial of 4,5-dichloro-2-(1-methyl-1H-pyrazol-4-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridine (Example 113C) (300 mg, 0.712 mmol) in anhydrous N,N-dimethylformamide (4 mL) was degassed by nitrogen sparge for about 20 minutes. The solution was treated with zinc cyanide (167 mg, 1.424 mmol) and tetrakis(triphenylphosphine)palladium (82 mg, 0.071 mmol). The reaction was degassed and back-filled with nitrogen, and heated in a Biotage Initiator microwave for 60 minutes at 160° C. The reaction was treated with additional zinc cyanide (83 mg, 0.712 mmol) and tetrakis(triphenylphosphine)palladium (41 mg, 0.035 mmol), and heated to 160° C. for 30 minutes by microwave irradiation. The reaction was diluted with water and ethyl acetate, and the layers were separated. The organic layer was washed with water and brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by flash chromatography on silica gel, eluting with a gradient of 25 to 40% ethyl acetate in hexanes, to provide the title compound. MS ESI(+) m/z 412.4 [M+H]+.

후처리

  1. customsparge for about 20 minutes
  2. customThe reaction was degassed
  3. additionback-filled with nitrogen
  4. temperatureheated to 160° C. for 30 minutes by microwave irradiation
  5. customthe layers were separated
  6. washThe organic layer was washed with water and brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by flash chromatography on silica gel
  11. washeluting with a gradient of 25 to 40% ethyl acetate in hexanes

출처 및 근거

ORD 기록
ord-e5d78e8b6bd040bda9b8770d2a77d9e0
출처 데이터셋
uspto-grants-2014_04
특허 번호
US08691810B2

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