Triethylamine → 4-(2-Fluoro-5-methoxycarbonyloxy-4-methylanilino)-7-methoxyacetamidoquinazoline

HRID 634726Notes

Reaction equation

HRID 634726 reaction equation
[CH3:1][O:2][CH2:3][C:4](Cl)=[O:5].C(N(CC)CC)C.Cl.[NH2:15][C:16]1[CH:25]=[C:24]2[C:19]([C:20]([NH:26][C:27]3[CH:32]=[C:31]([O:33][C:34]([O:36][CH3:37])=[O:35])[C:30]([CH3:38])=[CH:29][C:28]=3[F:39])=[N:21][CH:22]=[N:23]2)=[CH:18][CH:17]=1>C(Cl)Cl>[F:39][C:28]1[CH:29]=[C:30]([CH3:38])[C:31]([O:33][C:34]([O:36][CH3:37])=[O:35])=[CH:32][C:27]=1[NH:26][C:20]1[C:19]2[C:24](=[CH:25][C:16]([NH:15][C:4](=[O:5])[CH2:3][O:2][CH3:1])=[CH:17][CH:18]=2)[N:23]=[CH:22][N:21]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 96623Methoxyacetyl chlorideHCID 226250847-Amino4-(2-fluoro-5-methoxycarbonyloxy-4-methylanilino)quinazoline hydrochloride

Product 1

HCID 212603364-(2-Fluoro-5-methoxycarbonyloxy-4-methylanilino)-7-methoxyacetamidoquinazolineYield 60%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Methoxyacetyl chloride (119 mg, 1.1 mmol) followed by triethylamine (232 mg, 2.3 mmol) were added to a suspension of 7-amino-4-(2-fluoro-5-methoxycarbonyloxy-4-methylanilino)quinazoline hydrochloride (415 mg, 1.1 mmol) in methylene chloride (10 ml) and the mixture stirred for 1 hour. The solvent was removed by evaporation and the residue partitioned between ethyl acetate and water. The organic layer was separated, washed with brine, dried (MgSO4) and the solvent removed by evaporation. The resulting solid was purified by column chromatography eluting with methylene chloride/acetonitrile 50/50 followed by methylene chloride/acetonitrile/methanol 50/45/5 to give 4-(2-fluoro-5-methoxycarbonyloxy-4-methylanilino)-7-methoxyacetamidoquinazoline (250 mg, 60%) as a yellow solid.

Workup

  1. customThe solvent was removed by evaporation
  2. customthe residue partitioned between ethyl acetate and water
  3. customThe organic layer was separated
  4. washwashed with brine
  5. dry with materialdried (MgSO4)
  6. customthe solvent removed by evaporation
  7. customThe resulting solid was purified by column chromatography
  8. washeluting with methylene chloride/acetonitrile 50/50

Sources & evidence

ORD record
ord-e3806ae4f7c9436a94d6bc6ead3593e4
Source dataset
uspto-grants-2001_02
Patent number
US06184225B2

Reaction notes

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