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

HRID 242871

反応式

HRID 242871 の反応式
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

参加物

5

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 3776Isopropanol溶媒

反応条件

温度
80 °C

実験手順

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)

後処理

  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)

出典と根拠

ORDレコード
ord-9191c66092ee494e99e319879d9194a2
出典データセット
uspto-grants-2014_02
特許番号
US08653089B2

関連ノート

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