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 714556노트

반응식

HRID 714556 반응식
[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]

참가 물질

6

반응물 4

HCID 6328Methyl iodideHCID 12597IsosorbideHCID 24758Sodium hydride2회HCID 10640649N-(3-chloro-4-fluorophenyl)-7-fluoro-6-nitroquinazolin-4-amine

생성물 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

시약·촉매·용매 1

HCID 6228Dimethylformamide용매2회

반응 조건

온도
0 °C

실험 절차

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].

후처리

  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

출처 및 근거

ORD 기록
ord-b678eb49f7404b778f4f6edb480d20c4
출처 데이터셋
uspto-grants-2015_11
특허 번호
US09187459B2

반응 노트

불러오는 중…