Methyl iodide → N-(3-chloro-4-fluorophenyl)-7-(((3S,3aS,6R,6aS)-6-methoxyhexahydrofuro[3,2-b]furan-3-yl)oxy)-6-nitroquinazolin-4-amine

HRID 714556ノート

反応式

HRID 714556 の反応式
[H-].[Na+].[CH2:3]1[O:7][C@@H:6]2[C@@H:8]([OH:11])[CH2:9][O:10][C@@H:5]2[C@@H:4]1[OH:12].[CH3:13]I.[Cl:15][C:16]1[CH:17]=[C:18]([NH:23][C:24]2[C:33]3[C:28](=[CH:29][C:30](F)=[C:31]([N+:34]([O-:36])=[O:35])[CH:32]=3)[N:27]=[CH:26][N:25]=2)[CH:19]=[CH:20][C:21]=1[F:22]>CN(C=O)C>[Cl:15][C:16]1[CH:17]=[C:18]([NH:23][C:24]2[C:33]3[C:28](=[CH:29][C:30]([O:12][C@H:4]4[CH2:3][O:7][C@H:6]5[C@H:8]([O:11][CH3:13])[CH2:9][O:10][C@@H:5]45)=[C:31]([N+:34]([O-:36])=[O:35])[CH:32]=3)[N:27]=[CH:26][N:25]=2)[CH:19]=[CH:20][C:21]=1[F:22]

参加物

6

反応物 4

HCID 6328Methyl iodideHCID 12597IsosorbideHCID 24758Sodium hydride2 回HCID 10640649N-(3-chloro-4-fluorophenyl)-7-fluoro-6-nitroquinazolin-4-amine

生成物 1

HCID 71014288N-(3-chloro-4-fluorophenyl)-7-(((3S,3aS,6R,6aS)-6-methoxyhexahydrofuro[3,2-b]furan-3-yl)oxy)-6-nitroquinazolin-4-amine

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒2 回

反応条件

温度
0 °C

実験手順

NaH (60% dispersion in mineral oil, 493 mg, 12.32 mmol) was added in portions to a stirring solution of dianhydro-D-glucitol (1.5 g, 10.26 mmol) in DMF (20 mL) at room temperature under N2 (g) atmosphere. After 20 min, methyl iodide (639 μL, 10.26 mmol) was added, the mixture stirred for 30 min, cooled to 0° C., followed by stepwise addition of DMF (20 mL) and NaH (493 mg, 12.32 mmol). N-(3-chloro-4-fluorophenyl)-7-fluoro-6-nitroquinazolin-4-amine 1a (500 mg, 1.48 mmol, prepared according to Smaill, J. B., et al., Journal of Medicinal Chemistry, 2000, 43, 1380-1397) was added after 20 min and the reaction was quenched 30 min later at 0° C. by a slow addition of saturated NH4Cl, followed by extraction with EtOAc (100 mL). The organic layer was washed with H2O (2×100 mL), brine (100 mL), dried over MgSO4, and concentrated to a yellow residue 1b. MS m/z (ESI+), 477 [M+1].

後処理

  1. customthe reaction was quenched 30 min later at 0° C. by a slow addition of saturated NH4Cl
  2. extractionfollowed by extraction with EtOAc (100 mL)
  3. washThe organic layer was washed with H2O (2×100 mL), brine (100 mL)
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated to a yellow residue 1b

出典と根拠

ORDレコード
ord-b678eb49f7404b778f4f6edb480d20c4
出典データセット
uspto-grants-2015_11
特許番号
US09187459B2

反応ノート

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