Sodium hydride → (6S)-6-[(6-Chloro-3-pyridazinyl)methoxy]-2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine
反応式
[H-].[Na+].[N+:3]([C:6]1[N:7]=[C:8]2[N:13]([CH:14]=1)[CH2:12][C@H:11]([OH:15])[CH2:10][O:9]2)([O-:5])=[O:4].Br[CH2:17][C:18]1[N:19]=[N:20][C:21]([Cl:24])=[CH:22][CH:23]=1>CN(C=O)C>[Cl:24][C:21]1[N:20]=[N:19][C:18]([CH2:17][O:15][C@@H:11]2[CH2:10][O:9][C:8]3=[N:7][C:6]([N+:3]([O-:5])=[O:4])=[CH:14][N:13]3[CH2:12]2)=[CH:23][CH:22]=1参加物
反応物 3
生成物 1
試薬・触媒・溶媒 1
反応条件
- 温度
- -42 °C
実験手順
Sodium hydride (60% w/w, 0.30 g, 7.6 mmol) was added to a solution of (6S)-2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazin-6-ol (0.89 g, 4.8 mmol) in DMF (20 mL) at 0° C. The resultant solution was cooled to −42° C. and a solution of 3-(bromomethyl)-6-chloropyridazine (1.05 g, 5.1 mmol) in DMF (5 mL) was added. The mixture was stirred at −42° C. for 1 h and then quenched with ice. EtOAc (200 mL) was added, the organic layer was dried (MgSO4) and concentrated under reduced pressure. The residue was chromatographed on silica gel, initially eluting with hexanes/EtOAc (1:1) to remove unreacted 3-(bromomethyl)-6-chloropyridazine and then EtOAc to give the title compound (0.84 g, 56%) as a white solid. APCI MS m/z 312.6 (M+H). 1H NMR (400 MHz, (CD3)2SO) δ 8.02 (s, 1H), 7.93 (d, J=8.8 Hz, 1H), 7.74 (d, J=8.8 Hz, 1H), 4.97 (d, J=13.2 Hz, 1H), 4.94 (d, J=13.2 Hz, 1H), 4.69 (dt, J=12.0, 2.6 Hz, 1H), 4.50 (d, J=12.1 Hz, 1H), 4.30-4.39 (m, 2H), 4.25 (dd, J=13.5, 3.3 Hz, 1H).
後処理
- customquenched with ice
- additionEtOAc (200 mL) was added
- dry with materialthe organic layer was dried (MgSO4)
- concentrationconcentrated under reduced pressure
- customThe residue was chromatographed on silica gel
- washinitially eluting with hexanes/EtOAc (1:1)
- customto remove unreacted 3-(bromomethyl)-6-chloropyridazine
出典と根拠
- ORDレコード
- ord-2b946b02148241dc95d26731020b6f12
- 出典データセット
- uspto-grants-2010_02
- 特許番号
- US07666864B2
反応ノート
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