6-fluoro-2,3-dihydro-1H-indole → HCID 18932733, compound

HRID 1597920Notes

Reaction equation

HRID 1597920 reaction equation
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][CH2:7][NH:8]2)=[CH:4][CH:3]=1.Cl[C:12]1[C:21]2[C:16](=[CH:17][C:18]([O:24][CH3:25])=[C:19]([O:22][CH3:23])[CH:20]=2)[N:15]=[CH:14][N:13]=1>CC(O)C>[F:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][CH2:7][N:8]2[C:12]2[C:21]3[C:16](=[CH:17][C:18]([O:24][CH3:25])=[C:19]([O:22][CH3:23])[CH:20]=3)[N:15]=[CH:14][N:13]=2)=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 2604006-fluoro-2,3-dihydro-1H-indoleHCID 27693644-Chloro-6,7-dimethoxyquinazoline

Product 1

HCID 18932733HCID 18932733, compound

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

To 6-fluoroindoline (274 mg, 2.0 mmol) in dry i-PrOH (10mL) was added 4-chloro-6,7-dimethoxy-quinazoline (225 mg, 1.0 mmol). The mixture was refluxed for 16 hours under an atmosphere of dry N2(g) and then the solvent was removed in vacuo. The residue was partitioned between CHCl3 and 1M NaOH, and the organic phase was washed with brine, dried over Na2SO4(g) and concentrated in vacuo. The residue (535 mg) was purified by flash chromatography on silica using 80%EtOAc/CH2 Cl2 to yield 4-(6-fluoro-2,3-dihydro-indol-1-yl)-6,7-dimethoxyquinazoline as its free base (293 mg) (GC/MS: 325 (M+); LC-MS: 326 (MH+); anal. RP18-HPLC RT: 4.37 min.).

Workup

  1. temperatureThe mixture was refluxed for 16 hours under an atmosphere of dry N2(g)
  2. customthe solvent was removed in vacuo
  3. customThe residue was partitioned between CHCl3 and 1M NaOH
  4. washthe organic phase was washed with brine
  5. dry with materialdried over Na2SO4(g)
  6. concentrationconcentrated in vacuo
  7. customThe residue (535 mg) was purified by flash chromatography on silica using 80%EtOAc/CH2 Cl2

Sources & evidence

ORD record
ord-be2757e016e94b7a9b39b69f0430674d
Source dataset
uspto-grants-1998_04
Patent number
US05736534

Reaction notes

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