Dimethylcarbamoyl Chloride → 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-(N',N',N-trimethylureido)ethoxy)quinazoline hydrochloride

HRID 1838593Notes

Reaction equation

HRID 1838593 reaction equation
[CH3:1][N:2]([CH3:6])[C:3]([Cl:5])=[O:4].[Cl:7][C:8]1[CH:31]=[CH:30][C:11]([NH:12][C:13]2[C:22]3[C:17](=[CH:18][C:19]([O:25][CH2:26]CNC)=[C:20]([O:23][CH3:24])[CH:21]=3)[N:16]=[CH:15][N:14]=2)=[C:10]([F:32])[CH:9]=1.[CH2:33]([N:35](CC)[CH2:36]C)C>C(Cl)Cl>[ClH:5].[Cl:7][C:8]1[CH:31]=[CH:30][C:11]([NH:12][C:13]2[C:22]3[C:17](=[CH:18][C:19]([O:25][CH2:26][CH2:1][N:2]([CH3:6])[C:3]([N:35]([CH3:36])[CH3:33])=[O:4])=[C:20]([O:23][CH3:24])[CH:21]=3)[N:16]=[CH:15][N:14]=2)=[C:10]([F:32])[CH:9]=1

Participants

5

Reactant 3

HCID 6598Dimethylcarbamoyl ChlorideHCID 8471TriethylamineHCID 224781924-(4-Chloro-2-fluoroanilino)-6-methoxy-7-(2-methylaminoethoxy)quinazoline

Product 1

HCID 698084364-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-(N',N',N-trimethylureido)ethoxy)quinazoline hydrochlorideYield 41.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Dimethylcarbamyl chloride (38 μl, 0.42 mmol) was added to a solution of 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-methylaminoethoxy)quinazoline (150 mg, 0.4 mmol), (prepared as described for the starting material in Example 60), and triethylamine (61 μl, 0.44 mmol) in methylene chloride (4 ml). The mixture was stirred for 2.5 hours at ambient temperature, the resulting precipitate was collected by filtration and washed with ether. The solid was purified by column chromatography, eluting with methylene chloride/methanol (92/8). The purified product was dissolved in methylene chloride/methanol (1/1), 2.9M ethereal hydrogen chloride (1 ml) was added and the volatiles were removed by evaporation. The residue was triturated with ether and the solid product collected by filtration, washed with ether and dried under vacuum to give 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-(N′, N′, N-trimethylureido)ethoxy)quinazoline hydrochloride (80 mg, 41%).

Workup

  1. custom(prepared
  2. filtrationthe resulting precipitate was collected by filtration
  3. washwashed with ether
  4. customThe solid was purified by column chromatography
  5. washeluting with methylene chloride/methanol (92/8)
  6. dissolutionThe purified product was dissolved in methylene chloride/methanol (1/1)
  7. addition2.9M ethereal hydrogen chloride (1 ml) was added
  8. customthe volatiles were removed by evaporation
  9. customThe residue was triturated with ether
  10. filtrationthe solid product collected by filtration
  11. washwashed with ether
  12. customdried under vacuum

Sources & evidence

ORD record
ord-518a264e1c944052a47cd38cd0f65b0a
Source dataset
uspto-grants-2004_01
Patent number
US06673803B2

Reaction notes

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