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

HRID 914748노트

반응식

HRID 914748 반응식
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

참가 물질

4

반응물 2

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

생성물 1

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

시약·촉매·용매 1

HCID 1140Toluene용매

실험 절차

((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).

후처리

  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)

출처 및 근거

ORD 기록
ord-4172daa4651f4241b84437ceb651176d
출처 데이터셋
uspto-grants-2007_09
특허 번호
US07265115B2

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