Water → N-[(Z)-1-azabicyclo[3.2.2]nonan-4-ylideneamino]-6-bromo-N-methylpyridin-2-amine

HRID 1521472Notes

Reaction equation

HRID 1521472 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([N:8]([CH3:10])[NH2:9])[N:3]=1.[N:11]12[CH2:19][CH2:18][CH:15]([CH2:16][CH2:17]1)[C:14](=O)[CH2:13][CH2:12]2.C1(C)C=CC(S(O)(=O)=O)=CC=1.O>C1(C)C=CC=CC=1>[Br:1][C:2]1[N:3]=[C:4]([N:8]([CH3:10])/[N:9]=[C:14]2/[CH2:13][CH2:12][N:11]3[CH2:19][CH2:18][CH:15]/2[CH2:16][CH2:17]3)[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 962WaterHCID 6101p-Toluenesulfonic acidHCID 64203071-Azabicyclo[3.2.2]nonan-4-oneHCID 575147632-Bromo-6-(1-methylhydrazinyl)pyridine

Product 1

HCID 58079422N-[(Z)-1-azabicyclo[3.2.2]nonan-4-ylideneamino]-6-bromo-N-methylpyridin-2-amineYield 36.2%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A solution of 2-bromo-6-(1-methylhydrazinyl)pyridine (4.50 g, 22.2 mmol), 1-azabicyclo[3.2.2]nonan-4-one (3.00 g, 22.2 mmol) and p-toluenesulphonic acid (844 mg, 4.40 mmol) in toluene (140 mL) was heated under reflux, with water removal (azeotrope), for 4 h. The mixture was concentrated and made basic using saturated aqueous NaHCO3. The aqueous layer was extracted with methylene chloride (3×). The combined organic extracts were dried over Na2SO4, filtered and concentrated to dryness. The residue was purified by flash column chromatography (silica gel, 0%-100% solvent mixture B in methylene chloride; solvent mixture B=80:18:2 methylene chloride/methanol/concentrated ammonium hydroxide) to give the title compound (2.60 g, 36%) as a yellow oil: 1H NMR (500 MHz, CDCl3) δ 7.29 (t, J=8.0 Hz, 1H), 6.83 (d, J=7.0 Hz, 1H), 6.55 (d, J=8.5 Hz, 0.7H), 6.41 (d, J=8.5 Hz, 0.3 H), 3.20 (s, 3H), 3.17-2.94 (m, 7H), 2.80 (t, J=7.0 Hz, 0.6H), 2.73 (t, J=7.0 Hz, 1.4H), 1.89-1.85 (m, 3H), 1.74-1.60 (m, 1H).

Workup

  1. concentrationThe mixture was concentrated
  2. extractionThe aqueous layer was extracted with methylene chloride (3×)
  3. dry with materialThe combined organic extracts were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated to dryness
  6. customThe residue was purified by flash column chromatography (silica gel, 0%-100% solvent mixture B in methylene chloride; solvent mixture B=80:18:2 methylene chloride/methanol/concentrated ammonium hydroxide)

Sources & evidence

ORD record
ord-df0aee325db64630b938467b151d7c31
Source dataset
uspto-grants-2015_07
Patent number
US09073925B2

Reaction notes

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