4-Methylmorpholine → [4-({[2-(4-Fluoro-phenoxy)-pyridine-3-carbonyl]-amino}-methyl)-benzyl]-carbamic acid tert-butyl ester

HRID 354098

Reaction equation

HRID 354098 reaction equation
[F:1][C:2]1[CH:17]=[CH:16][C:5]([O:6][C:7]2[N:15]=[CH:14][CH:13]=[CH:12][C:8]=2[C:9]([OH:11])=O)=[CH:4][CH:3]=1.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[C:40]([O:44][C:45](=[O:56])[NH:46][CH2:47][C:48]1[CH:53]=[CH:52][C:51]([CH2:54][NH2:55])=[CH:50][CH:49]=1)([CH3:43])([CH3:42])[CH3:41].CN1CCOCC1>CN(C)C=O>[C:40]([O:44][C:45](=[O:56])[NH:46][CH2:47][C:48]1[CH:49]=[CH:50][C:51]([CH2:54][NH:55][C:9]([C:8]2[C:7]([O:6][C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:17][CH:16]=3)=[N:15][CH:14]=[CH:13][CH:12]=2)=[O:11])=[CH:52][CH:53]=1)([CH3:43])([CH3:41])[CH3:42]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 6051232-(4-Fluorophenoxy)nicotinic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 3354775tert-butyl N-{[4-(aminomethyl)phenyl]methyl}carbamate

Product 1

HCID 20738633[4-({[2-(4-Fluoro-phenoxy)-pyridine-3-carbonyl]-amino}-methyl)-benzyl]-carbamic acid tert-butyl esterYield 81.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-(4-Fluoro-phenoxy)-nicotinic acid (see reference Patent application WO 98/45268) (6.20 g, 26 mmol), 1-hydroxybenzotriazole (5.39 g, 40 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (6.62 g, 34 mmol) were disolved in N,N-dimethylformamide (50 ml) at room temperature and (4-aminomethyl-benzyl)-carbamic acid tert-butyl ester (6.28 g, 26 mmol) (see Preparation 1) added followed by addition of N-methyl morpholine (4.4 ml, 40 mmol). The reaction mixture was stirred under an atmosphere of nitrogen at room temperature for 18 hours, and then partitioned between ethyl acetate (100 ml) and water (100 ml) and the organic layer separated. The organic phase was then washed with a saturated aqueous solution of sodium chloride (100 ml), dried over anhydrous magnesium sulphate and the solvent removed in vacuo. The residue was triturated with diethylether (15 ml) giving [4-({[2-(4-fluoro-phenoxy)-pyridine-3-carbonyl]-amino}-methyl)-benzyl]-carbamic acid tert-butyl ester (9.52 g) as an off-white solid.

Workup

  1. custompartitioned between ethyl acetate (100 ml) and water (100 ml)
  2. customthe organic layer separated
  3. washThe organic phase was then washed with a saturated aqueous solution of sodium chloride (100 ml)
  4. dry with materialdried over anhydrous magnesium sulphate
  5. customthe solvent removed in vacuo
  6. customThe residue was triturated with diethylether (15 ml)

Sources & evidence

ORD record
ord-9a573d39a2d34264b5aee21f5cfce8e7
Source dataset
uspto-grants-2004_06
Patent number
US06756392B2

Linked notes

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