Triethylamine → 2-[3-(ethylsulfanyl)phenoxy]-5-fluoro-N-[(1S,2R)-2-hydroxycyclohexyl]nicotinamide

HRID 724297Notes

Reaction equation

HRID 724297 reaction equation
[CH2:1]([S:3][C:4]1[CH:5]=[C:6]([CH:18]=[CH:19][CH:20]=1)[O:7][C:8]1[N:16]=[CH:15][C:14]([F:17])=[CH:13][C:9]=1[C:10]([OH:12])=O)[CH3:2].C(N(CC)CC)C.[NH2:28][C@H:29]1[CH2:34][CH2:33][CH2:32][CH2:31][C@H:30]1[OH:35].Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1>CN(C)C=O>[NH3:16].[CH2:1]([S:3][C:4]1[CH:5]=[C:6]([CH:18]=[CH:19][CH:20]=1)[O:7][C:8]1[N:16]=[CH:15][C:14]([F:17])=[CH:13][C:9]=1[C:10]([NH:28][C@H:29]1[CH2:34][CH2:33][CH2:32][CH2:31][C@H:30]1[OH:35])=[O:12])[CH3:2]

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 6542151cis-2-AminocyclohexanolHCID 21877135HCID 21877135, compound

Product 2

HCID 222AmmoniaHCID 587462032-[3-(ethylsulfanyl)phenoxy]-5-fluoro-N-[(1S,2R)-2-hydroxycyclohexyl]nicotinamideYield 34.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-[3-(Ethylsulfanyl)phenoxy]-5-fluoronicotinic acid (250 mg, 0.85 mmol) was dissolved in dimethylformamide (5 ml) and triethylamine (475 μl, 3.41 mmol) was added followed by (1R,2S)-2-aminocyclohexanol hydroformate (144 mg, 0.89 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (180 mg, 0.94 mmol) and 1-hydroxybenzotriazole (127 mg, 0.94 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 water (5 ml) and ethyl acetate (10 ml) and the aqueous phase was extracted with ethyl acetate (3×10 ml). The combined organic extracts were washed with brine (5 ml), dried over MgSO4 and the solvent was removed under reduced pressure. The residue was purified by flash column chromatography using dichloromethane:methanol:0.880 ammonia (98:2:0.2) as eluant to give 2-[3-(ethylsulfanyl)phenoxy]-5-fluoro-N-[(1S,2R)-2-hydroxycyclohexyl]nicotinamide (57 mg) as a colourless oil.

Workup

  1. customthe solvent was removed under reduced pressure
  2. customThe residue was partitioned between water (5 ml) and ethyl acetate (10 ml)
  3. extractionthe aqueous phase was extracted with ethyl acetate (3×10 ml)
  4. washThe combined organic extracts were washed with brine (5 ml)
  5. dry with materialdried over MgSO4
  6. customthe solvent was removed under reduced pressure
  7. customThe residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-1358cfb99c9d464d99a7fc74bec414bd
Source dataset
uspto-grants-2006_11
Patent number
US07141586B2

Reaction notes

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