Acetic Acid → 4-(2-Fluoro-5-methoxycarbonyloxy-4-methylanilino)-7-(2-(imidazol-1-yl)ethoxy)-6-methoxyquinazoline

HRID 279556

Reaktionsgleichung

Reaktionsgleichung von HRID 279556
N(C(OCC)=O)=NC(OCC)=O.Cl.[F:14][C:15]1[CH:34]=[C:33]([CH3:35])[C:32]([O:36][C:37]([O:39][CH3:40])=[O:38])=[CH:31][C:16]=1[NH:17][C:18]1[C:27]2[C:22](=[CH:23][C:24]([OH:30])=[C:25]([O:28][CH3:29])[CH:26]=2)[N:21]=[CH:20][N:19]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[N:60]1([CH2:65][CH2:66]O)[CH:64]=[CH:63][N:62]=[CH:61]1.C(O)(=O)C>C(Cl)Cl>[F:14][C:15]1[CH:34]=[C:33]([CH3:35])[C:32]([O:36][C:37]([O:39][CH3:40])=[O:38])=[CH:31][C:16]=1[NH:17][C:18]1[C:27]2[C:22](=[CH:23][C:24]([O:30][CH2:66][CH2:65][N:60]3[CH:64]=[CH:63][N:62]=[CH:61]3)=[C:25]([O:28][CH3:29])[CH:26]=2)[N:21]=[CH:20][N:19]=1

Komponenten

7

Edukt 5

HCID 176Acetic AcidHCID 11776TriphenylphosphineHCID 74168N-(2-Hydroxyethyl)imidazoleHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 1356711794-(2-Fluoro-5-methoxycarbonyloxy-4-methylanilino)-7-hydroxy-6-methoxyquinazoline hydrochloride

Produkt 1

HCID 226250254-(2-Fluoro-5-methoxycarbonyloxy-4-methylanilino)-7-(2-(imidazol-1-yl)ethoxy)-6-methoxyquinazolineAusbeute 76,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

Diethyl azodicarboxylate (160 mg, 1.4 mmol) was added to a solution of 4-(2-fluoro-5-methoxycarbonyloxy-4-methylanilino)-7-hydroxy-6-methoxyquinazoline hydrochloride (261 mg, 0.7 mmol), (prepared as described for the starting material in Example 22), triphenylphosphine (367 mg, 1.4 mmol) and 2-(imidazol-1-yl)ethanol (94 mg, 0.84 mmol), (J. Med. Chem. 1993, 25, 4052-4060), in methylene chloride (5 ml) and the mixture stirred for 1 hour at ambient temperature. Acetic acid (42 mg, 0.7 mmol) was added and the solvent was removed by evaporation. The residue was triturated with ether, the solid collected by filtration, dried under vacuum and purified by chromatography eluting with methylene chloride/methanol (9/1 followed by 8/2) to give 4-(2-fluoro-5-methoxycarbonyloxy-4-methylanilino)-7-(2-(imidazol-1-yl)ethoxy)-6-methoxyquinazoline (250 mg, 76%).

Aufarbeitung

  1. custom(prepared
  2. customthe solvent was removed by evaporation
  3. customThe residue was triturated with ether
  4. filtrationthe solid collected by filtration
  5. customdried under vacuum
  6. custompurified by chromatography
  7. washeluting with methylene chloride/methanol (9/1 followed by 8/2)

Quellen und Nachweise

ORD-Eintrag
ord-b09be4b4f04f4c91b265718ae24c509e
Quelldatensatz
uspto-grants-2002_03
Patentnummer
US06362336B1

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