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

HRID 354096

Reaction equation

HRID 354096 reaction equation
[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

Participants

7

Reactant 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

Product 1

HCID 98699872-(4-fluoro-phenoxy)-N-{4-[(2-hydroxy-3-methyl-benzoylamino)-methyl]-benzyl}-nicotinamideYield 21.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-01723da6fbc74ae49dc25a9a05cbd2ec
Source dataset
uspto-grants-2004_06
Patent number
US06756392B2

Linked notes

Loading…