Sodium Hydroxide → 7-({2-[(4-Methoxybenzyl)(methyl)amino]pyridin-4-yl}oxy)-1,2,3,4-tetrahydronaphthalene-2-carboxylic acid

HRID 1640201

Reaction equation

HRID 1640201 reaction equation
Cl[C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:18]=[C:17]3[C:12]([CH2:13][CH2:14][CH:15]([C:19]([OH:21])=[O:20])[CH2:16]3)=[CH:11][CH:10]=2)[CH:5]=[CH:4][N:3]=1.[CH3:22][O:23][C:24]1[CH:29]=[CH:28][C:27]([CH2:30][NH:31][CH3:32])=[CH:26][CH:25]=1.[OH-].[Na+]>CN1C(=O)CCC1.O.Cl>[CH3:22][O:23][C:24]1[CH:29]=[CH:28][C:27]([CH2:30][N:31]([CH3:32])[C:2]2[CH:7]=[C:6]([O:8][C:9]3[CH:18]=[C:17]4[C:12]([CH2:13][CH2:14][CH:15]([C:19]([OH:21])=[O:20])[CH2:16]4)=[CH:11][CH:10]=3)[CH:5]=[CH:4][N:3]=2)=[CH:26][CH:25]=1

Participants

7

Reactant 3

HCID 14798Sodium HydroxideHCID 4854071-(4-methoxyphenyl)-N-methylmethanamineHCID 580552117-[(2-Chloropyridin-4-yl)oxy]-1,2,3,4-tetrahydronaphthalene-2-carboxylic acid

Product 1

HCID 589023697-({2-[(4-Methoxybenzyl)(methyl)amino]pyridin-4-yl}oxy)-1,2,3,4-tetrahydronaphthalene-2-carboxylic acidYield 28.1%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A solution of 7-[(2-chloropyridin-4-yl)oxy]-1,2,3,4-tetrahydronaphthalene-2-carboxylic acid (1.50 g, 4.94 mmol) and 1-(4-methoxyphenyl)-N-methylmethanamine (2.24 g, 14.8 mmol) in NMP (9 mL) was heated in a sealed tube at 150° C. for 40 hr. The reaction mixture was allowed to cool to rt and diluted with water and 1N HCl solution. The pH was adjusted to 4 by the addition of 1N NaOH solution. The mixture was extracted with EtOAc (3×) and the organic solutions were combined, washed with water and brine, dried over Na2SO4 and concentrated. The residue was purified by column chromatography to give 7-({2-[(4-methoxybenzyl)(methyl)amino]pyridin-4-yl}oxy)-1,2,3,4-tetrahydronaphthalene-2-carboxylic acid as an off-white solid (581 mg, 28.1%). LCMS: (FA) ES+ 419.2, ES− 417.2.

Workup

  1. extractionThe mixture was extracted with EtOAc (3×)
  2. washwashed with water and brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-81f6a882c628487f8f32469a9ea9132c
Source dataset
uspto-grants-2012_02
Patent number
US08110687B2

Linked notes

Loading…