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Triethylamine → (5-Chloro-6-{4-[6-(4-fluoro-phenyl)-2-(2-methyl-pyrrolidin-1-yl)-pyrimidin-4-yl]-piperazine-1-yl}-pyridin-3-yl)-acetonitrile

HRID 2195031
ノート
印刷プレビュー

反応式

HRID 2195031 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]([CH2:33]O)[CH:5]=[N:6][C:7]=1[N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[C:18]([C:20]3[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=3)[N:17]=[C:16]([N:27]3[CH2:31][CH2:30][CH2:29][CH:28]3[CH3:32])[N:15]=2)[CH2:10][CH2:9]1.C[CH2:36][N:37](CC)CC.CS(Cl)(=O)=O>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([CH2:33][C:36]#[N:37])[CH:5]=[N:6][C:7]=1[N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[C:18]([C:20]3[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=3)[N:17]=[C:16]([N:27]3[CH2:31][CH2:30][CH2:29][CH:28]3[CH3:32])[N:15]=2)[CH2:10][CH2:9]1
参加物実験手順後処理出典と根拠反応ノート

参加物

5

反応物 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 11670243(5-Chloro-6-{4-[6-(4-fluoro-phenyl)-2-(2-methyl-pyrrolidin-1-yl)pyrimidin-4-yl]-piperazin-1-yl}-pyridin-3-yl)-methanol

生成物 1

HCID 66838806(5-Chloro-6-{4-[6-(4-fluoro-phenyl)-2-(2-methyl-pyrrolidin-1-yl)-pyrimidin-4-yl]-piperazine-1-yl}-pyridin-3-yl)-acetonitrile

試薬・触媒・溶媒 1

HCID 6344
Dichloromethane
溶媒
2 回

実験手順

To an ice cooled solution of (5-chloro-6-{4-[6-(4-fluoro-phenyl)-2-(2-methyl-pyrrolidin-1-yl)-pyrimidin-4-yl]-piperazin-1-yl}-pyridin-3-yl)-methanol (136 mg, 0.282 mmol) and Et3N (79 μL, 0.564 mmol) in DCM, add MsCl (33 μL, 0.422 mmol) dropwise. Remove ice bath and stir for 1 h at room temperature. Dilute with 3 volumes of DCM, wash with brine, dry the organic layer (Na2SO4) and concentrate under reduced pressure. Dissolve the crude mesylate in DMSO, add 138 mg of NaCN and heat at 60° C. until no starting material remains as indicated by TLC. Dilute with water and extract the aqueous solution with EtOAc. Wash the organic extract with water (2×) followed by brine (1×), dry (Na2SO4) and concentrate under reduced pressure to give crude product. Purify using flash chromatography to give pure title compound.

後処理

  1. washwash with brine
  2. dry with materialdry the organic layer (Na2SO4)
  3. concentrationconcentrate under reduced pressure
  4. dissolutionDissolve the crude mesylate in DMSO
  5. additionadd 138 mg of NaCN
  6. temperatureheat at 60° C. until no starting material
  7. additionDilute with water
  8. extractionextract the aqueous solution with EtOAc
  9. washWash the
  10. extractionorganic extract with water (2×)
  11. dry with materialdry (Na2SO4)
  12. concentrationconcentrate under reduced pressure
  13. customto give crude product
  14. customPurify

出典と根拠

ORDレコード
ord-ba3ea3c7ae8b47e99f0e7b44a7917bd5
出典データセット
uspto-grants-2012_12
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08334382B2

反応ノート

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