Triethylamine → 3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-{[methoxy-(2-methoxy-acetyl)-amino]-methyl}-benzamide

HRID 20766

Reaktionsgleichung

Reaktionsgleichung von HRID 20766
[CH3:1][O:2][CH2:3][C:4]([OH:6])=O.ON1C(=O)C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[F:31][C:32]1[C:33]([NH:50][C:51]2[CH:56]=[CH:55][C:54]([I:57])=[CH:53][C:52]=2[F:58])=[C:34]([CH:42]=[C:43]([CH2:46][NH:47][O:48][CH3:49])[C:44]=1[F:45])[C:35]([NH:37][O:38][CH2:39][CH2:40][OH:41])=[O:36].C(N(CC)CC)C>C(Cl)Cl.C1COCC1.C(OCC)(=O)C>[F:31][C:32]1[C:33]([NH:50][C:51]2[CH:56]=[CH:55][C:54]([I:57])=[CH:53][C:52]=2[F:58])=[C:34]([CH:42]=[C:43]([CH2:46][N:47]([O:48][CH3:49])[C:4](=[O:6])[CH2:3][O:2][CH3:1])[C:44]=1[F:45])[C:35]([NH:37][O:38][CH2:39][CH2:40][OH:41])=[O:36]

Komponenten

9

Edukt 5

HCID 8471TriethylamineHCID 12251Methoxyacetic AcidHCID 730263-hydroxy-1,2,3-benzotriazin-4(3H)-oneHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 115335813,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-(methoxyamino-methyl)-benzamide

Produkt 1

HCID 115705873,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-{[methoxy-(2-methoxy-acetyl)-amino]-methyl}-benzamideAusbeute 34 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6344DichloromethaneLösungsmittelHCID 8028TetrahydrofuranLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

To a solution of methoxyacetic acid (9.0 μl, 0.12 mmol) in methylene chloride (1 ml) were added 3-hydroxy-4-oxo-3,4-dihydro-1,2,3-benzotriazine (18.9 mg, 0.12 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (22.5 mg, 0.12 mmol), and the mixture was stirred for 3 hours. This solution was added dropwise to a solution of 3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-(methoxyamino-methyl)-benzamide (50.0 mg, 0.10 mmol) obtained in Example 15 in THF (3 ml), and triethylamine (40.9 μl, 0.29 mmol) was added thereto. The mixture was stirred for 15 hours. The reaction mixture was diluted with ethyl acetate (45 ml), and washed with saturated aqueous ammonium chloride (20 ml), and then with saturated brine (2×20 ml). The organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resultant residue was purified by preparative TLC (CH2Cl2/MeOH (10:1)) to give 3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-{[methoxy-(2-methoxy-acetyl)-amino]-methyl}-benzamide (Compound F-6, 19.1 mg, 34%) as a colorless oil.

Aufarbeitung

  1. additionwas added
  2. stirringThe mixture was stirred for 15 hours
  3. washwashed with saturated aqueous ammonium chloride (20 ml)
  4. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe resultant residue was purified by preparative TLC (CH2Cl2/MeOH (10:1))

Quellen und Nachweise

ORD-Eintrag
ord-5987972dc41345a4a5c7a0139d3a5d35
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07745663B2

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