Dimethylformamide → HCID 57619200, compound

HRID 1256802Notes

Reaction equation

HRID 1256802 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([NH:9][CH2:10][C:11]2[CH:12]=[N:13][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:15][CH:16]=2)=[N:6][C:7]=1[Cl:8].C([Mg]Cl)(C)C.C([Li])(C)(C)C.CN(C)[CH:33]=[O:34]>O1CCCC1.O>[Cl:8][C:7]1[C:2]([CH:33]=[O:34])=[CH:3][CH:4]=[C:5]([NH:9][CH2:10][C:11]2[CH:12]=[N:13][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:15][CH:16]=2)[N:6]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 57619448HCID 57619448, compoundHCID 178418306HCID 178418306, compoundHCID 178418918HCID 178418918, compound

Product 1

HCID 57619200HCID 57619200, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To (5-bromo-6-chloro-pyridin-2-yl)-(6-trifluoromethyl-pyridin-3-ylmethyl)-amine (568, 4.60 g, 0.0125 mol) in tetrahydrofuran (60.0 mL) under an atmosphere of nitrogen at −78° C., isopropylmagnesium chloride (2.00 M in tetrahydrofuran, 6.44 mL) was added over 10 minutes. The reaction was stirred at −78° C. for 20 minutes, and then allowed to warm to room temperature for 10 minutes. The reaction was cooled to −78° C., followed by adding tert-butyllithium (1.70 M in hexane, 15.3 mL) over 10 minutes. After 40 minutes, N,N-dimethylformamide (1.23 mL, 0.0158 mol) was added and the reaction was stirred at −78° C. for 40 minutes, then allowed to warm to room temperature for 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 (569, 2.84 g, 71.7%).

Workup

  1. temperatureto warm to room temperature for 10 minutes
  2. temperatureThe reaction was cooled to −78° C.
  3. waitAfter 40 minutes
  4. stirringthe reaction was stirred at −78° C. for 40 minutes
  5. temperatureto warm to room temperature for 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 (569, 2.84 g, 71.7%)

Sources & evidence

ORD record
ord-c3b3d091531947088c31a09b4d935c05
Source dataset
uspto-grants-2013_06
Patent number
US08461169B2

Reaction notes

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