3-Pyridinemethanamine → (1R,4R)-2-[(4-methylphenyl)sulfonyl]-5-(3-pyridinylmethyl)-2,5-diazabicyclo[2.2.1]heptane

HRID 914748Notes

Reaction equation

HRID 914748 reaction equation
CC1C=CC(S(O[CH2:12][C@H:13]2[CH2:17][C@H:16](OS(C3C=CC(C)=CC=3)(=O)=O)[CH2:15][N:14]2[S:29]([C:32]2[CH:37]=[CH:36][C:35]([CH3:38])=[CH:34][CH:33]=2)(=[O:31])=[O:30])(=O)=O)=CC=1.[NH2:39][CH2:40][C:41]1[CH:42]=[N:43][CH:44]=[CH:45][CH:46]=1>C1(C)C=CC=CC=1>[CH3:38][C:35]1[CH:34]=[CH:33][C:32]([S:29]([N:14]2[CH2:15][C@H:16]3[CH2:17][C@@H:13]2[CH2:12][N:39]3[CH2:40][C:41]2[CH:42]=[N:43][CH:44]=[CH:45][CH:46]=2)(=[O:30])=[O:31])=[CH:37][CH:36]=1

Participants

4

Reactant 2

HCID 310183-PyridinemethanamineHCID 15629272((2R,4S)-1-[(4-Methylphenyl)sulfonyl]-4-{[(4-methylphenyl)sulfonyl]oxy}pyrrolidinyl)methyl 4-methylbenzenesulfonate

Product 1

HCID 16747987(1R,4R)-2-[(4-methylphenyl)sulfonyl]-5-(3-pyridinylmethyl)-2,5-diazabicyclo[2.2.1]heptaneYield 46%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

((2R,4S)-1-[(4-Methylphenyl)sulfonyl]-4-{[(4-methylphenyl)sulfonyl]oxy}pyrrolidinyl)methyl 4-methylbenzenesulfonate (1.5 g, 2.6 mmol), prepared as described in (J. Med. Chem. (1990) 33, 1344) and 3-(aminomethyl)pyridine (1.0 g, 9.3 mmol) in 20 mL of toluene were heated under reflux for 16 hours. The mixture was cooled, filtered, and the filter cake was washed with 20 mL of toluene. The filtrate was concentrated under reduced pressure and the residue was purified by chromatography (silica gel; hexanes:EtOAc, 9:1 to 1:1) to provide the title compound (410 mg, 46%). 1H NMR (DMSO-d6, 300 MHz) δ 0.86 (d, J=8.5 Hz, 1H), 1.62 (d, J=9.7 Hz, 1H), 2.42 (s, 3H), 2.44 (m, 1H), 2.66 (dd, J=2.4, 9.5 Hz, 1H), 2.99 (dd, J=2.0, 9.5 Hz, 1H), 3.39-3.48 (m, 2H), 3.62-3.41 (d, J=9.5 Hz, 1H), 4.23 (br s, 1H), 4.35 (t, J=5.1 Hz, 1H), 7.31 (m, 1H), 7.43-7.46 (m, 2H), 7.62 (m, 1H), 7.71-7.74 (m, 2H), 8.31-8.43 (m, 2H).

Workup

  1. temperaturewere heated
  2. temperatureunder reflux for 16 hours
  3. temperatureThe mixture was cooled
  4. filtrationfiltered
  5. washthe filter cake was washed with 20 mL of toluene
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. customthe residue was purified by chromatography (silica gel; hexanes:EtOAc, 9:1 to 1:1)

Sources & evidence

ORD record
ord-4172daa4651f4241b84437ceb651176d
Source dataset
uspto-grants-2007_09
Patent number
US07265115B2

Reaction notes

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