Dimethylformamide → 6-Cyano-2-(2-fluoro-4-trimethylsilanyl-phenylamino)-nicotinic acid methyl ester

HRID 1500668ノート

反応式

HRID 1500668 の反応式
[CH3:1][O:2][C:3](=[O:23])[C:4]1[CH:9]=[CH:8][C:7](Cl)=[N:6][C:5]=1[NH:11][C:12]1[CH:17]=[CH:16][C:15]([Si:18]([CH3:21])([CH3:20])[CH3:19])=[CH:14][C:13]=1[F:22].[CH3:24][N:25](C)C=O>[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>[CH3:1][O:2][C:3](=[O:23])[C:4]1[CH:9]=[CH:8][C:7]([C:24]#[N:25])=[N:6][C:5]=1[NH:11][C:12]1[CH:17]=[CH:16][C:15]([Si:18]([CH3:21])([CH3:20])[CH3:19])=[CH:14][C:13]=1[F:22]

参加物

5

反応物 2

HCID 6228DimethylformamideHCID 591401556-Chloro-2-(2-fluoro-4-trimethylsilanyl-phenylamino)-nicotinic acid methyl ester

生成物 1

HCID 591401856-Cyano-2-(2-fluoro-4-trimethylsilanyl-phenylamino)-nicotinic acid methyl ester

試薬・触媒・溶媒 2

HCID 11186Zinc cyanide (Zn(CN)2)触媒HCID 178418397HCID 178418397、化合物触媒

実験手順

A degassed suspension of 6-chloro-2-(2-fluoro-4-trimethylsilanyl-phenylamino)-nicotinic acid methyl ester (4.8 g, 12.4 mmol), zinc cyanide (1.2 g, 10.2 mmol), and Pd(PPh3)4 (1.6 g, 1.36 mmol) in dimethylformamide (14 mL) was subjected to microwave irradiation at 190° C. for 20 minutes. This procedure was repeated seven times and all the reaction mixtures were combined and concentrated in vacuo. The resultant residue was dissolved in ethyl acetate and washed with a saturated aqueous solution of sodium hydrogen carbonate. The aqueous layer was separated and extracted with ethyl acetate three times. The combined organic extracts were washed with water and then brine, dried (Na2SO4), filtered and evaporated in vacuo. The resultant residue was subjected to flash chromatography (silica, gradient 0% to 100%, diethyl ether in pentane) to afford the title compound as a yellow solid (18.2 g). LCMS (method B): RT=4.74 min, M+H+=344.

後処理

  1. customirradiation at 190° C. for 20 minutes
  2. customthe reaction mixtures
  3. concentrationconcentrated in vacuo
  4. dissolutionThe resultant residue was dissolved in ethyl acetate
  5. washwashed with a saturated aqueous solution of sodium hydrogen carbonate
  6. customThe aqueous layer was separated
  7. extractionextracted with ethyl acetate three times
  8. washThe combined organic extracts were washed with water
  9. dry with materialbrine, dried (Na2SO4)
  10. filtrationfiltered
  11. customevaporated in vacuo

出典と根拠

ORDレコード
ord-abc55acf969b4aebbc964eccd3670489
出典データセット
uspto-grants-2015_12
特許番号
US09206174B2

反応ノート

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