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 714556Notes

Reaction equation

HRID 714556 reaction equation
[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]

Participants

6

Reactant 4

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

Product 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

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

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].

Workup

  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

Sources & evidence

ORD record
ord-b678eb49f7404b778f4f6edb480d20c4
Source dataset
uspto-grants-2015_11
Patent number
US09187459B2

Reaction notes

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