4-Fluoroaniline → 3-Amino-9-((4-fluoroanilino)methyl)benzo[f]quinazolin-1(2H)-one

HRID 381605Notes

Reaction equation

HRID 381605 reaction equation
Br[CH2:2][C:3]1[CH:4]=[CH:5][C:6]2[CH:15]=[CH:14][C:13]3[N:12]=[C:11]([NH:16]C(=O)C(C)(C)C)[NH:10][C:9](=[O:23])[C:8]=3[C:7]=2[CH:24]=1.[F:25][C:26]1[CH:32]=[CH:31][C:29]([NH2:30])=[CH:28][CH:27]=1.C(=O)(O)[O-].[Na+]>CN(C)C=O>[NH2:16][C:11]1[NH:10][C:9](=[O:23])[C:8]2[C:7]3[CH:24]=[C:3]([CH2:2][NH:30][C:29]4[CH:31]=[CH:32][C:26]([F:25])=[CH:27][CH:28]=4)[CH:4]=[CH:5][C:6]=3[CH:15]=[CH:14][C:13]=2[N:12]=1

Participants

5

Reactant 3

HCID 97314-FluoroanilineHCID 516892Sodium BicarbonateHCID 135525312N-(9-Bromomethyl-1,2-dihydro-1-oxobenzo[f]quinazolin-3-yl)pivalamide

Product 1

HCID 1358382193-Amino-9-((4-fluoroanilino)methyl)benzo[f]quinazolin-1(2H)-oneYield 36.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

N-(9-Bromomethyl-1,2-dihydro-1-oxobenzo[f]quinazolin-3-yl)pivalamide (0.97 g, 2.5 mmole) and 4-fluoroaniline (0.56 g, 5 mmole) (Aldrich) were dissolved in dimethylformamide (15 ml). The reaction was stirred for 30 minutes at 100° C., sodium bicarbonate (0.42 g, 5mmole) added and the suspension stirred for a further 30 minutes. The dimethyl-formamide was removed in vacuo, the residue washed with methylene chloride and filtered. The filtrate was evaporated, and the residue was subjected to chromatography on a Waters Prep 500 instrument (silica cartridge, elution with ethyl acetate/methylene chloride (1:19)). Fractions containing product were concentrated in vacuo, the residue dissolved in a minimum amount of ethyl acetate, and the solution diluted with hexane until precipitate formed. The solid was collected by filtration and dried under high vacuum to give the title compound as a beige solid (0.305 g,29%). 1H NMR (DMSO-d6, 200 MHz) δ: 1.25 (s, 9H, t-butyl); 4.42 (d, J=6 Hz,2H, CH2); 6.33 (t,J=6 Hz, 1H, NH); 6.53-6.60 (m, 2H, Ar); 6.85 (t, J=8 Hz, 2H, Ar); 7.50 (d, J=10 Hz, 1H, Ar); 7.60 (dd, J=8, 2 Hz, 1H, Ar); 7.96 (d, J=8 Hz, 1H, Ar); 8.19 (d, J=8 Hz, 1H, Ar); 9.72 (s, 1H, Ar); 11.23 (s, 1H, NH); 12.28 (s, 1H, NH).

Workup

  1. stirringthe suspension stirred for a further 30 minutes
  2. customThe dimethyl-formamide was removed in vacuo
  3. washthe residue washed with methylene chloride
  4. filtrationfiltered
  5. customThe filtrate was evaporated
  6. washthe residue was subjected to chromatography on a Waters Prep 500 instrument (silica cartridge, elution with ethyl acetate/methylene chloride (1:19))
  7. additionFractions containing product
  8. concentrationwere concentrated in vacuo
  9. dissolutionthe residue dissolved in a minimum amount of ethyl acetate
  10. additionthe solution diluted with hexane until precipitate
  11. customformed
  12. filtrationThe solid was collected by filtration
  13. customdried under high vacuum

Sources & evidence

ORD record
ord-3565dcef1d894f5a9695768c16230364
Source dataset
uspto-grants-2001_10
Patent number
US06306865B1

Reaction notes

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