Dimethylformamide → 6-{4-[6-(4-Fluoro-phenyl)-2-(2-(S)-methyl-pyrrolidin-1-yl)-pyrimidin-4-yl]-3-(R)-methyl-piperazin-1-yl}-5-chloro-nicotinonitrile

HRID 2195084ノート

反応式

HRID 2195084 の反応式
Br[C:2]1[CH:3]=[C:4]([Cl:34])[C:5]([N:8]2[CH2:13][CH2:12][N:11]([C:14]3[CH:19]=[C:18]([C:20]4[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=4)[N:17]=[C:16]([N:27]4[CH2:31][CH2:30][CH2:29][C@@H:28]4[CH3:32])[N:15]=3)[C@H:10]([CH3:33])[CH2:9]2)=[N:6][CH:7]=1.[CH3:35][N:36](C=O)C>[C-]#N.[C-]#N.[Zn+2].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>[F:26][C:23]1[CH:24]=[CH:25][C:20]([C:18]2[N:17]=[C:16]([N:27]3[CH2:31][CH2:30][CH2:29][C@@H:28]3[CH3:32])[N:15]=[C:14]([N:11]3[CH2:12][CH2:13][N:8]([C:5]4[C:4]([Cl:34])=[CH:3][C:2]([C:35]#[N:36])=[CH:7][N:6]=4)[CH2:9][C@H:10]3[CH3:33])[CH:19]=2)=[CH:21][CH:22]=1

参加物

5

反応物 2

HCID 6228DimethylformamideHCID 591683424-[4-(5-Bromo-3-chloro-pyridin-2-yl)-2-(R)-methyl-piperazin-1-yl]-6-(4-fluoro-phenyl)-2-(2-(S)-methyl-pyrrolidin-1-yl)-pyrimidine

生成物 1

HCID 591683766-{4-[6-(4-Fluoro-phenyl)-2-(2-(S)-methyl-pyrrolidin-1-yl)-pyrimidin-4-yl]-3-(R)-methyl-piperazin-1-yl}-5-chloro-nicotinonitrile

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

To a mixture of 4-[4-(5-bromo-3-chloro-pyridin-2-yl)-2-(R)-methyl-piperazin-1-yl]-6-(4-fluoro-phenyl)-2-(2-(S)-methyl-pyrrolidin-1-yl)-pyrimidine (700 mg) and Zn(CN)2 (94 mg) in DMF, add Pd(PPh3)4 (77 mg, 0.067 mmol). Purge the reaction mixture for 10 min with dry N2. Heat the stirring reaction mixture overnight at 80° C., cool to room temperature and partition between water and EtOAc. Dry the solution (Na2SO4), concentrate under reduced pressure. Purify the residue by flash column eluting with EtOAc-Hexanes (1:1) to afford the title compound as a white solid.

後処理

  1. customPurge the reaction mixture for 10 min with dry N2
  2. temperatureHeat
  3. customthe stirring reaction mixture overnight at 80° C.
  4. custompartition between water and EtOAc
  5. dry with materialDry the solution (Na2SO4)
  6. concentrationconcentrate under reduced pressure
  7. customPurify the residue by flash column
  8. washeluting with EtOAc-Hexanes (1:1)

出典と根拠

ORDレコード
ord-d0727776d03e412fb1f5d72e1ec6da3a
出典データセット
uspto-grants-2012_12
特許番号
US08334382B2

反応ノート

読み込み中…