3-Methylsalicylic Acid → 2-(4-fluoro-phenoxy)-N-{4-[(2-hydroxy-3-methyl-benzoylamino)-methyl]-benzyl}-nicotinamide

HRID 354096

Reaktionsgleichung

Reaktionsgleichung von HRID 354096
[OH:1][C:2]1[C:10]([CH3:11])=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.Cl.[NH2:35][CH2:36][C:37]1[CH:61]=[CH:60][C:40]([CH2:41][NH:42][C:43](=[O:59])[C:44]2[CH:49]=[C:48](F)[CH:47]=[N:46][C:45]=2[O:51][C:52]2[CH:57]=[CH:56][C:55]([F:58])=[CH:54][CH:53]=2)=[CH:39][CH:38]=1.CN1CCOCC1>CN(C)C=O>[F:58][C:55]1[CH:54]=[CH:53][C:52]([O:51][C:45]2[N:46]=[CH:47][CH:48]=[CH:49][C:44]=2[C:43]([NH:42][CH2:41][C:40]2[CH:60]=[CH:61][C:37]([CH2:36][NH:35][C:4](=[O:6])[C:3]3[CH:7]=[CH:8][CH:9]=[C:10]([CH3:11])[C:2]=3[OH:1])=[CH:38][CH:39]=2)=[O:59])=[CH:57][CH:56]=1

Komponenten

7

Edukt 5

HCID 67383-Methylsalicylic AcidHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 23512939N-(4-aminomethyl-benzyl)-5-fluoro-2-(4-fluoro-phenoxy)-nicotinamide hydrochloride

Produkt 1

HCID 98699872-(4-fluoro-phenoxy)-N-{4-[(2-hydroxy-3-methyl-benzoylamino)-methyl]-benzyl}-nicotinamideAusbeute 21,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

A solution of 2-Hydroxy-3-methylbenzoic acid (118 mg, 0.773 mmol), 1-hydroxybenzotriazole (157 mg, 1.16 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (193 mg, 1.01 mmol), N-(4-aminomethyl-benzyl)-5-fluoro-2-(4-fluoro-phenoxy)-nicotinamide hydrochloride (300 mg, 0.773 mmol) (see Preparation 3) and N-methyl morpholine (0.17 ml, 1.55 mmol) in N,N-dimethylformamide (6 ml) was stirred under nitrogen at room temperature for 18 hours. The mixture was then partitioned between ethyl acetate (10 ml) and water (10 ml). The organic phase was separated, washed with a saturated aqueous solution of sodium chloride (10 ml) and dried over anhydrous magnesium sulphate. The solvent was then removed in vacuo and the residue was triturated with diethylether (3-fold 10 ml) giving 2-(4-fluoro-phenoxy)-N-{4-[(2-hydroxy-3-methyl-benzoylamino)-methyl]-benzyl}-nicotinamide (80 mg) as an off-white foam.

Aufarbeitung

  1. customThe mixture was then partitioned between ethyl acetate (10 ml) and water (10 ml)
  2. customThe organic phase was separated
  3. washwashed with a saturated aqueous solution of sodium chloride (10 ml)
  4. dry with materialdried over anhydrous magnesium sulphate
  5. customThe solvent was then removed in vacuo
  6. customthe residue was triturated with diethylether (3-fold 10 ml)

Quellen und Nachweise

ORD-Eintrag
ord-01723da6fbc74ae49dc25a9a05cbd2ec
Quelldatensatz
uspto-grants-2004_06
Patentnummer
US06756392B2

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