Triethylamine → 5-fluoro-N-(2-hydroxy-2-methylcyclohexyl)-2-[3-(methylsulfanyl)phenoxy]nicotinamide

HRID 724299Notes

Reaction equation

HRID 724299 reaction equation
[CH3:1][S:2][C:3]1[CH:4]=[C:5]([CH:17]=[CH:18][CH:19]=1)[O:6][C:7]1[N:15]=[CH:14][C:13]([F:16])=[CH:12][C:8]=1[C:9]([OH:11])=O.C(N(CC)CC)C.Cl.[NH2:28][CH:29]1[CH2:34][CH2:33][CH2:32][CH2:31][C:30]1([CH3:36])[OH:35].Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1>CN(C)C=O>[F:16][C:13]1[CH:14]=[N:15][C:7]([O:6][C:5]2[CH:17]=[CH:18][CH:19]=[C:3]([S:2][CH3:1])[CH:4]=2)=[C:8]([CH:12]=1)[C:9]([NH:28][CH:29]1[CH2:34][CH2:33][CH2:32][CH2:31][C:30]1([OH:35])[CH3:36])=[O:11]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 113918232-[3-(Methylsulfanyl)phenoxy]-5-fluoronicotinic acidHCID 218771592-Amino-1-methylcyclohexanol hydrochloride

Product 1

HCID 218771395-fluoro-N-(2-hydroxy-2-methylcyclohexyl)-2-[3-(methylsulfanyl)phenoxy]nicotinamideYield 100.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-[3-(Methylsulfanyl)phenoxy]-5-fluoronicotinic acid (100 mg, 0.358 mmol) was dissolved in dimethylformamide (5 ml) and triethylamine (250 μl, 3.41 mmol) was added followed by 2-amino-1-methylcyclohexanol hydrochloride (65 mg, 0.39 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (205 mg, 1.07 mmol) and 1-hydroxybenzotriazole (53 mg, 0.39 mmol). The reaction was stirred under nitrogen at room temperature for 18 h and the solvent was removed under reduced pressure. The residue was partitioned between 10% aq. citric acid solution and diethyl ether. The organic was washed with sat. sodium bicarbonate solution, water and brine, dried over MgSO4 and the solvent was removed under reduced pressure. The residue was purified by flash column chromatography using ethyl acetate:cyclohexane (5:95 to 50:50) as eluant to give 5-fluoro-N-(2-hydroxy-2-methylcyclohexyl)-2-[3-(methylsulfanyl)phenoxy]nicotinamide (140 mg) as a gum.

Workup

  1. customthe solvent was removed under reduced pressure
  2. customThe residue was partitioned between 10% aq. citric acid solution and diethyl ether
  3. washThe organic was washed with sat. sodium bicarbonate solution, water and brine
  4. dry with materialdried over MgSO4
  5. customthe solvent was removed under reduced pressure
  6. customThe residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-b195494b0f3a44209b57a460d53db667
Source dataset
uspto-grants-2006_11
Patent number
US07141586B2

Reaction notes

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