Diisopropylethylamine → [(S)-1-(6-Fluoro-1-phenyl-1H-benzoimidazol-2-yl)ethyl]-[9-(tetrahydropyran-2-yl)-9H-purin-6-yl]amine

HRID 242871

반응식

HRID 242871 반응식
Cl.Cl.[F:3][C:4]1[CH:5]=[CH:6][C:7]2[N:11]=[C:10]([C@@H:12]([NH2:14])[CH3:13])[N:9]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[C:8]=2[CH:21]=1.Cl[C:23]1[N:31]=[CH:30][N:29]=[C:28]2[C:24]=1[N:25]=[CH:26][N:27]2[CH:32]1[CH2:37][CH2:36][CH2:35][CH2:34][O:33]1.CCN(C(C)C)C(C)C>CC(O)C>[F:3][C:4]1[CH:5]=[CH:6][C:7]2[N:11]=[C:10]([C@@H:12]([NH:14][C:23]3[N:31]=[CH:30][N:29]=[C:28]4[C:24]=3[N:25]=[CH:26][N:27]4[CH:32]3[CH2:37][CH2:36][CH2:35][CH2:34][O:33]3)[CH3:13])[N:9]([C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:8]=2[CH:21]=1

참가 물질

5

반응물 3

HCID 81531DiisopropylethylamineHCID 977406-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purineHCID 68157580(S)-1-(6-Fluoro-1-phenyl-1H-benzoimidazol-2-yl)ethylamine dihydrochloride

생성물 1

HCID 68157440[(S)-1-(6-Fluoro-1-phenyl-1H-benzoimidazol-2-yl)ethyl]-[9-(tetrahydropyran-2-yl)-9H-purin-6-yl]amine수율 70%

시약·촉매·용매 1

HCID 3776Isopropanol용매

반응 조건

온도
80 °C

실험 절차

To a solution of (S)-1-(6-fluoro-1-phenyl-1H-benzoimidazol-2-yl)ethylamine dihydrochloride (30.7 g, 93.7 mmol) in IPA (300 mL) was added 6-chloro-9-(tetrahydropyran-2-yl)-9H-purine (26.9 g, 112.5 mmol) and DIPEA (48 mL, 281.2 mmol) and the reaction mixture heated at 80° C. for 16 h. The reaction mixture was concentrated in vacuo and the residue dissolved in EtOAc (600 mL). The solution was washed with water and the organic fraction separated. The organic fraction was washed with brine, dried (MgSO4) and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, eluting with 0-10% methanol in EtOAc) to yield the title compound as a yellow oil (30 g, 70%) 1H NMR 400 MHz (CDCl3) δ 8.25 (1H, s), 7.96 (1H, s), 7.70 (1H, qn, J=4.1 Hz), 7.37-7.58 (5H, m), 6.98-6.82 (1H, m), 6.52-6.66 (1H, m), 5.60-5.77 (2H, m), 4.12-4.19 (1H, m), 3.76 (1H, td, J 11.3, 2.5 Hz), 1.91-2.13 (4H, m), 1.68-1.84 (2H, m), 1.60-1.68 (3H, m)

후처리

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. dissolutionthe residue dissolved in EtOAc (600 mL)
  3. washThe solution was washed with water
  4. customthe organic fraction separated
  5. washThe organic fraction was washed with brine
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. washThe resultant residue was subjected to flash chromatography (SiO2, eluting with 0-10% methanol in EtOAc)

출처 및 근거

ORD 기록
ord-9191c66092ee494e99e319879d9194a2
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08653089B2

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