Acetone → 2-([N-(2-methoxyethyl)-N-methylamino)ethoxy)quinazoline hydrochloride

HRID 2182569Notes

Reaction equation

HRID 2182569 reaction equation
[CH2:1]([N:3]([CH2:6][CH3:7])[CH2:4][CH3:5])C.C[O:9][CH2:10]CBr.[Cl:13]C1C=CC(N[C:19]2[C:28]3[C:23](=[CH:24][C:25](OCCNC)=[C:26](OC)[CH:27]=3)[N:22]=[CH:21][N:20]=2)=C(F)C=1.CC(C)=[O:41]>>[ClH:13].[CH3:10][O:9][CH2:5][CH2:4][N:3]([CH2:6][CH2:7][O:41][C:21]1[N:20]=[CH:19][C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[N:22]=1)[CH3:1]

Participants

5

Reactant 4

HCID 180Acetone2×HCID 8471TriethylamineHCID 809722-Bromoethyl methyl etherHCID 224781924-(4-Chloro-2-fluoroanilino)-6-methoxy-7-(2-methylaminoethoxy)quinazoline

Product 1

HCID 867597412-([N-(2-methoxyethyl)-N-methylamino)ethoxy)quinazoline hydrochlorideYield 16%

Conditions

Temperature
50 °C

Procedure

Triethylamine (44 μl, 0.32 mmol) and then a solution of 2-bromoethyl methyl ether (40 mg, 0.29 mmol) in acetone (0.5 ml) was added dropwise to a solution of 4{4-chloro-2-fluoroanilino)-6-methoxy-7-(2-methylaminoethoxy)quinazoline (100 mg, 0.26 mmol) in acetone (2.5 ml) heated at 50° C. under nitrogen. The mixture was stirred for 7 hours at 50° C., the mixture was allowed to cool and partitioned between ethyl acetate and water. The organic layer was separated, washed with brine, dried (MgSO4) and the volatiles removed by evaporation. The residue was purified by column chromatography eluting with methylene chloride/methanol (92/8). The purified product was dissolved in methylene chloride, insolubles were removed by filtration and 2.2M ethereal hydrogen chloride (0.5 ml) was added to the filtrate. The volatiles were removed by evaporation and the residue was triturated with ether, collected by filtration and dried under vacuum to give 4-(4-chloro-2-fluoroanilino)6-methoxy-7-(2-([N-(2-methoxyethyl)-N-methylamino)ethoxy)quinazoline hydrochloride (22 mg, 16%).

Workup

  1. temperatureto cool
  2. custompartitioned between ethyl acetate and water
  3. customThe organic layer was separated
  4. washwashed with brine
  5. dry with materialdried (MgSO4)
  6. customthe volatiles removed by evaporation
  7. customThe residue was purified by column chromatography
  8. washeluting with methylene chloride/methanol (92/8)
  9. dissolutionThe purified product was dissolved in methylene chloride
  10. custominsolubles were removed by filtration and 2.2M ethereal hydrogen chloride (0.5 ml)
  11. additionwas added to the filtrate
  12. customThe volatiles were removed by evaporation
  13. customthe residue was triturated with ether
  14. filtrationcollected by filtration
  15. customdried under vacuum

Sources & evidence

ORD record
ord-f87f21a0781641ac81a366326d6e2239
Source dataset
uspto-grants-2005_05
Patent number
US06897210B2

Reaction notes

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