Triethylamine → 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-(N-methyl-N-(4-pyridylcarbonyl)amino)ethoxy)quinazoline hydrochloride

HRID 1420984Notes

Reaction equation

HRID 1420984 reaction equation
[C:1]([Cl:9])(=[O:8])[C:2]1[CH:7]=[CH:6][N:5]=[CH:4][CH:3]=1.O.Cl.[Cl:12][C:13]1[CH:36]=[CH:35][C:16]([NH:17][C:18]2[C:27]3[C:22](=[CH:23][C:24]([O:30][CH2:31][CH2:32][NH:33][CH3:34])=[C:25]([O:28][CH3:29])[CH:26]=3)[N:21]=[CH:20][N:19]=2)=[C:15]([F:37])[CH:14]=1.C(N(CC)CC)C>C(Cl)Cl>[ClH:9].[Cl:12][C:13]1[CH:36]=[CH:35][C:16]([NH:17][C:18]2[C:27]3[C:22](=[CH:23][C:24]([O:30][CH2:31][CH2:32][N:33]([CH3:34])[C:1]([C:2]4[CH:7]=[CH:6][N:5]=[CH:4][CH:3]=4)=[O:8])=[C:25]([O:28][CH3:29])[CH:26]=3)[N:21]=[CH:20][N:19]=2)=[C:15]([F:37])[CH:14]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 417436Pyridine-4-carbonyl chlorideHCID 226249694-(4-Chloro-2-fluoroanilino)-6-methoxy-7-(2-(methylamino)ethoxy)quinazoline hydrochloride hydrate

Product 1

HCID 226250114-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-(N-methyl-N-(4-pyridylcarbonyl)amino)ethoxy)quinazoline hydrochlorideYield 144.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Isonicotinoyl chloride (36 mg, 0.2 mmol) was added to a suspension of 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-(methylamino)ethoxy)quinazoline hydrochloride hydrate (90 mg, 0.1 mmol), (prepared as described for the starting material in Example 54), in methylene chloride (3 ml) and triethylamine (80 mg, 0.8 mmol) was then added dropwise. The mixture was stirred for 30 minutes at ambient temperature and the solvent was then removed by evaporation. The residue was partitioned between ethyl acetate and water, the organic layer was separated, washed with brine, dried (MgSO4) and the solvent removed by evaporation. The residue was dissolved in methylene chloride/methanol and 3M ethereal hydrogen chloride (0.5 ml) was added. The suspension was diluted with ether, the precipitate was collected by filtration, washed with ether and dried under vacuum to give 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-(N-methyl-N-(4-pyridylcarbonyl)amino)ethoxy)quinazoline hydrochloride (75 mg, 67%).

Workup

  1. custom(prepared
  2. customthe solvent was then removed by evaporation
  3. customThe residue was partitioned between ethyl acetate and water
  4. customthe organic layer was separated
  5. washwashed with brine
  6. dry with materialdried (MgSO4)
  7. customthe solvent removed by evaporation
  8. dissolutionThe residue was dissolved in methylene chloride/methanol
  9. addition3M ethereal hydrogen chloride (0.5 ml) was added
  10. additionThe suspension was diluted with ether
  11. filtrationthe precipitate was collected by filtration
  12. washwashed with ether
  13. customdried under vacuum

Sources & evidence

ORD record
ord-091a59758a114721a20ab1e299d89c6c
Source dataset
uspto-grants-2000_06
Patent number
US06071921

Reaction notes

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