Dimethylformamide → 2-Chloro-6-(4-chloro-benzylamino)-pyridine-3-carbaldehyde

HRID 1754729Notes

Reaction equation

HRID 1754729 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([NH:9][CH2:10][C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=2)=[N:6][C:7]=1[Cl:8].C([Mg]Cl)(C)C.C([Li])(C)(C)C.CN(C)[CH:30]=[O:31]>O1CCCC1.O>[Cl:8][C:7]1[C:2]([CH:30]=[O:31])=[CH:3][CH:4]=[C:5]([NH:9][CH2:10][C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=2)[N:6]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 57619309(5-Bromo-6-chloro-pyridin-2-yl)-(4-chloro-benzyl)-amineHCID 178418306HCID 178418306, compoundHCID 178418918HCID 178418918, compound

Product 1

HCID 576192992-Chloro-6-(4-chloro-benzylamino)-pyridine-3-carbaldehyde

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To (5-bromo-6-chloro-pyridin-2-yl)-(4-chloro-benzyl)-amine (539, 2.60 g, 7.83 mmol) in tetrahydrofuran (60.0 mL) under an atmosphere of nitrogen at −78° C., isopropylmagnesium chloride (2.00 M in tetrahydrofuran, 4.20 mL) was added over 10 minutes. The reaction was stirred at −78° C. for 20 minutes, then allowed to warm to room temperature for 10 minutes. The reaction was cooled to −78° C. tert-Butyllithium (1.70 M in hexane, 10.2 mL) was added to the reaction over 10 minutes. After 40 minutes, N,N-dimethylformamide (1.80 mL, 0.0232 mol) was added to the reaction. The reaction was stirred at −78° C. for 40 minutes, then allowed to warm to room temperature for another 30 minutes. The reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, concentrated and purified by silica gel column chromatography eluting with 35% to 100% ethyl acetate in hexane to give a light yellow solid (540, 1.0 g, 45.4%). MS (ESI) [M−H+]−=279.0.

Workup

  1. temperatureto warm to room temperature for 10 minutes
  2. additionwas added to the reaction over 10 minutes
  3. waitAfter 40 minutes
  4. stirringThe reaction was stirred at −78° C. for 40 minutes
  5. temperatureto warm to room temperature for another 30 minutes
  6. extractionextracted with ethyl acetate
  7. washThe organic layer was washed with brine
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated
  10. custompurified by silica gel column chromatography
  11. washeluting with 35% to 100% ethyl acetate in hexane
  12. customto give a light yellow solid (540, 1.0 g, 45.4%)

Sources & evidence

ORD record
ord-8a3b1b3ebb694065be31871ebee778f0
Source dataset
uspto-grants-2015_10
Patent number
US09169250B2

Reaction notes

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