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

HRID 914748ノート

反応式

HRID 914748 の反応式
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

参加物

4

反応物 2

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒

実験手順

((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).

後処理

  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)

出典と根拠

ORDレコード
ord-4172daa4651f4241b84437ceb651176d
出典データセット
uspto-grants-2007_09
特許番号
US07265115B2

反応ノート

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