2-(4-Fluorophenoxy)nicotinic acid → 4'-[[[2-[4-Fluorophenoxy]-pyridine-3-carbonyl]-amino]-methyl]-biphenyl-3-carboxylic acid methyl ester

HRID 480085Notes

Reaction equation

HRID 480085 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.[CH3:18][O:19][C:20]([C:22]1[CH:23]=[C:24]([C:28]2[CH:33]=[CH:32][C:31]([CH2:34][NH2:35])=[CH:30][CH:29]=2)[CH:25]=[CH:26][CH:27]=1)=[O:21].O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>CN(C)C=O.O>[CH3:18][O:19][C:20]([C:22]1[CH:23]=[C:24]([C:28]2[CH:33]=[CH:32][C:31]([CH2:34][NH:35][C:9]([C:8]3[C:7]([O:6][C:5]4[CH:4]=[CH:3][C:2]([F:1])=[CH:17][CH:16]=4)=[N:15][CH:14]=[CH:13][CH:12]=3)=[O:11])=[CH:30][CH:29]=2)[CH:25]=[CH:26][CH:27]=1)=[O:21]

Participants

7

Reactant 4

HCID 6051232-(4-Fluorophenoxy)nicotinic acidHCID 1394186Methyl 3-[4-(aminomethyl)phenyl]benzoateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrate

Product 1

HCID 206014024'-[[[2-[4-Fluorophenoxy]-pyridine-3-carbonyl]-amino]-methyl]-biphenyl-3-carboxylic acid methyl esterYield 54.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 290 mg (1.24 mmol.) 2-[4-fluoro-phenoxy]-nicotinic acid, 300 mg (1.24 mmol.) 4′-aminomethyl-biphenyl-3-carboxylic acid methyl ester and 184 mg (1.36 mmol.) 1-hydroxybenzotriazole hydrate in 10 mL dimethylformamide at ambient temperature was added 285 mg (1.49 mmol.) 1-[3-[dimethylamino]propyl]-3-ethylcarbodiimide hydrochloride. The mixture was stirred at ambient temperature for 18 hours then poured into water and extracted with ethyl acetate. The ethyl acetate extracts were combined, washed successively with 1N NaOH, water, brine then dried (MgSO4) and concentrated in vacuo to give an oil. Chromatography on silica Gel eluting with ethyl acetate/hexanes (1:1) gave 310 mg 4′-[[[2-[4-Fluorophenoxy]-pyridine-3-carbonyl]-amino]-methyl]-biphenyl-3-carboxylic acid methyl ester as an oil.

Workup

  1. extractionextracted with ethyl acetate
  2. washwashed successively with 1N NaOH, water, brine
  3. dry with materialthen dried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. customto give an oil

Sources & evidence

ORD record
ord-5e901c401e3a4ac7ae12ee2c2ea0142e
Source dataset
uspto-grants-2003_11
Patent number
US06649633B2

Reaction notes

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