Ammonia → 5-chloro-3-(2,6-difluoro-pyridin-3-ylmethyl)-1H-pyrrolo[2,3-b]pyridine

HRID 1024245ノート

反応式

HRID 1024245 の反応式
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[N:3]=1.C([Li])CCC.C([Cu])#N.C(OC([N:24]1[C:28]2=[N:29][CH:30]=[C:31]([Cl:33])[CH:32]=[C:27]2[C:26]([CH2:34]Cl)=[CH:25]1)=O)(C)(C)C.N>O1CCCC1.CCCCCC.O>[Cl:33][C:31]1[CH:32]=[C:27]2[C:26]([CH2:34][C:7]3[C:2]([F:1])=[N:3][C:4]([F:8])=[CH:5][CH:6]=3)=[CH:25][NH:24][C:28]2=[N:29][CH:30]=1

参加物

9

反応物 5

HCID 222AmmoniaHCID 739342,6-DifluoropyridineHCID 576192411-Boc-5-chloro-3-(chloromethyl)-7-azaindoleHCID 178418339ButyllithiumHCID 178418546HCID 178418546、化合物

生成物 1

HCID 576193535-chloro-3-(2,6-difluoro-pyridin-3-ylmethyl)-1H-pyrrolo[2,3-b]pyridine

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒3 回HCID 8058Hexane溶媒

反応条件

温度
-78 °C

実験手順

To 2,6-Difluoropyridine (58, 3.40 g, 0.0295 mol) in tetrahydrofuran (200.0 mL), under an atmosphere of nitrogen at −78° C., 2.50M of n-butyllithium in hexane (12.0 mL) was added slowly. After 60 minutes, CuCN.2LiCl (0.75M in tetrahydrofuran, 40.0 mL) was added to the reaction mixture. After 5 minutes, 5-chloro-3-chloromethyl-pyrrolo[2,3-b]pyridine-1-carboxylic acid tert-butyl ester (535, 4.20 g, 0.0139 mol, prepared as described in Example 49, Scheme 164) in tetrahydrofuran (20 mL) was added to the reaction. The reaction was stirred at −78° C. overnight, then poured into water and ammonia (10 mL), and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography eluting with 15% ethyl acetate in hexane to give a white solid (P-0155, 300 mg, 7.7%). MS (ESI) [M−H+]−=278.1.

後処理

  1. waitAfter 5 minutes
  2. extractionextracted with ethyl acetate
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated
  6. custompurified by silica gel column chromatography
  7. washeluting with 15% ethyl acetate in hexane
  8. customto give a white solid (P-0155, 300 mg, 7.7%)

出典と根拠

ORDレコード
ord-802938af14254143ae292d683b8811a4
出典データセット
uspto-grants-2014_05
特許番号
US08722702B2

反応ノート

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