Hydrochloric Acid → 3-(2-Chloro-pyridin-4-yl)-3-(5-difluoromethoxy-4,6-dimethyl-pyridin-2-yl)-7-fluoro-3H-isoindol-1-ylamine

HRID 1662217ノート

反応式

HRID 1662217 の反応式
C([Li])CCC.Br[C:7]1[N:12]=[C:11]([CH3:13])[C:10]([O:14][CH:15]([F:17])[F:16])=[C:9]([CH3:18])[CH:8]=1.[Cl:19][C:20]1[CH:25]=[C:24]([C:26]([C:34]2[CH:39]=[CH:38][CH:37]=[C:36]([F:40])[C:35]=2[C:41]#[N:42])=[N:27]S(C(C)(C)C)=O)[CH:23]=[CH:22][N:21]=1.Cl.C(=O)(O)[O-].[Na+]>C1COCC1.CO.ClCCl>[Cl:19][C:20]1[CH:25]=[C:24]([C:26]2([C:7]3[CH:8]=[C:9]([CH3:18])[C:10]([O:14][CH:15]([F:17])[F:16])=[C:11]([CH3:13])[N:12]=3)[C:34]3[C:35](=[C:36]([F:40])[CH:37]=[CH:38][CH:39]=3)[C:41]([NH2:42])=[N:27]2)[CH:23]=[CH:22][N:21]=1

参加物

9

反応物 5

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 585795136-Bromo-3-difluoromethoxy-2,4-dimethyl-pyridineHCID 76821601N-[(2-Chloropyridin-4-yl)(2-cyano-3-fluorophenyl)methylidene]-2-methylpropane-2-sulfinamideHCID 178418339Butyllithium

生成物 1

HCID 585795123-(2-Chloro-pyridin-4-yl)-3-(5-difluoromethoxy-4,6-dimethyl-pyridin-2-yl)-7-fluoro-3H-isoindol-1-ylamine収率 36%

試薬・触媒・溶媒 3

HCID 887Methanol溶媒HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran溶媒2 回

実験手順

n-Butyllithium (2.5 M in hexane, 0.144 mL, 0.36 mmol) was added dropwise to a solution of 6-bromo-3-difluoromethoxy-2,4-dimethyl-pyridine (0.29 g, 1.15 mmol) in dry THF (1 mL) at −78° C. The reaction mixture was stirred for 5 minutes and a solution of N-[(2-chloro-4-pyridyl)-(2-cyano-3-fluoro-phenyl)methylene]-2-methyl-propane-2-sulfinamide (0.28 g, 0.77 mmol) in dry THF (1 mL) was added dropwise at −78° C. The stirring was continued for 1 hour, a solution of HCl in CH3OH (1.25M, 1.1 mL) was added dropwise at −78° C. and the mixture was allowed to warm slowly to room temperature and stirred overnight. Dichloromethane (20 mL) and saturated sodium bicarbonate solution (50 mL) were added and the phases separated. The organic layer was washed with H2O, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by flash column chromatography using 5% CH3OH in DCM to afford the title compound (120 mg, 36%).

後処理

  1. waitThe stirring was continued for 1 hour
  2. stirringstirred overnight
  3. customthe phases separated
  4. washThe organic layer was washed with H2O
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by flash column chromatography

出典と根拠

ORDレコード
ord-cd31d931946f4422bf702b5f7f95a99e
出典データセット
uspto-grants-2011_10
特許番号
US08030500B2

反応ノート

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