3-Chloro-4-fluoroaniline → 2-chloro-N-(3-chloro-4-fluorophenyl)-6-iodoquinazolin-4-amine

HRID 1520355Notes

Reaction equation

HRID 1520355 reaction equation
[Cl:1][C:2]1[N:11]=[C:10](Cl)[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([I:13])[CH:8]=2)[N:3]=1.[Cl:14][C:15]1[CH:16]=[C:17]([CH:19]=[CH:20][C:21]=1[F:22])[NH2:18].C([O-])(=O)C.[Na+]>C1COCC1.O>[Cl:1][C:2]1[N:11]=[C:10]([NH:18][C:17]2[CH:19]=[CH:20][C:21]([F:22])=[C:15]([Cl:14])[CH:16]=2)[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([I:13])[CH:8]=2)[N:3]=1

Participants

6

Reactant 3

HCID 97083-Chloro-4-fluoroanilineHCID 517045Sodium AcetateHCID 114615062,4-Dichloro-6-iodoquinazoline

Product 1

HCID 866770782-chloro-N-(3-chloro-4-fluorophenyl)-6-iodoquinazolin-4-amineYield 73.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

In a 50 mL round-bottomed flask was added 2,4-dichloro-6-iodoquinazoline (0.52 g, 1.6 mmol), 3-chloro-4-fluoroaniline (0.30 g, 2.1 mmol), and sodium acetate (0.20 g, 2.4 mmol) in THF (6 mL) and water (2 mL) to give a brown suspension. After being stirred at room temperature for 6 days, the reaction mixture was diluted with water (15 mL) and extracted with ethyl acetate (2×10 mL). The organic layers were combined and washed with brine (1×20 mL), dried over Na2SO4, filtered and concentrated. The resulting product, was washed with CH2Cl2 and dried to give 0.51 g of 2-chloro-N-(3-chloro-4-fluorophenyl)-6-iodoquinazolin-4-amine as a tight brown solid in a 73% yield, 1H NMR (300 MHz, DMSO) δ 10.29 (s, 1H), 8.95 (s, 1H), 8.14 (dd, J=1.5, 9.0 Hz, 1H), 8.06 (dd, J=2.7, 6.6 Hz, 1H), 7.81-7.76 (m, 1H), 7.52-7.46 (m, 2H).

Workup

  1. customto give a brown suspension
  2. extractionextracted with ethyl acetate (2×10 mL)
  3. washwashed with brine (1×20 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. washThe resulting product, was washed with CH2Cl2
  8. customdried

Sources & evidence

ORD record
ord-1997590d9f0d42768bfd3544f5f6c2e1
Source dataset
uspto-grants-2015_07
Patent number
US09073890B2

Reaction notes

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