Triethylamine → HCID 178503203, compound

HRID 724313Notes

Reaction equation

HRID 724313 reaction equation
[NH2:1][C@H:2]1[CH2:7][CH2:6][C@H:5]([CH2:8][OH:9])[CH2:4][CH2:3]1.C(N(CC)CC)C.[F:17][C:18]1[CH:19]=[N:20][C:21]([O:27][C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([S:34][CH3:35])[CH:29]=2)=[C:22]([CH:26]=1)[C:23](O)=[O:24].Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1>CN(C)C=O>[F:17][C:18]1[CH:19]=[N:20][C:21]([O:27][C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([S:34][CH3:35])[CH:29]=2)=[C:22]([CH:26]=1)[C:23]([NH:1][C@H:2]1[CH2:7][CH2:6][C@H:5]([CH2:8][OH:9])[CH2:4][CH2:3]1)=[O:24]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 113918232-[3-(Methylsulfanyl)phenoxy]-5-fluoronicotinic acidHCID 178511560HCID 178511560, compound

Product 1

HCID 178503203HCID 178503203, compoundYield 28.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

(trans-4-Amino-cyclohexyl)-methanol (73 mg, 0.56 mmol) and triethylamine (225□l, 1.61 mmol) were dissolved in dimethylformamide (225 μl) and a solution of 5-fluoro-2-(3-methylsulfanyl-phenoxy)-nicotinic acid (150 mg, 0.54 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (113 mg, 0.59 mmol) and 1-hydroxybenzotriazole (80 mg, 0.59 mmol) in dimethylformamide (5 ml) was added. The reaction was stirred under nitrogen at room temperature for 64 h and the solvent was removed under reduced pressure. The residue was partitioned between 0.5N HCl (10 ml) and ethyl acetate (10 ml) and the aqueous phase was extracted with ethyl acetate (2×10 ml). The combined organic phases were washed with brine (10 ml), dried over MgSO4 and the solvent was removed under reduced pressure. The residue was purified by flash column chromatography on silica gel eluting with dichloromethane:methanol:concentrated aqueous ammonia (97.5:2.5:0.25, by volume). The product was triturated with ethyl acetate (3 ml) to give 5-Fluoro-N-(trans-4-hydroxymethyl-cyclohexyl)-2-(3-methylsulfanyl-phenoxy)-nicotinamide (60 mg) as a white solid.

Workup

  1. customthe solvent was removed under reduced pressure
  2. customThe residue was partitioned between 0.5N HCl (10 ml) and ethyl acetate (10 ml)
  3. extractionthe aqueous phase was extracted with ethyl acetate (2×10 ml)
  4. washThe combined organic phases were washed with brine (10 ml)
  5. dry with materialdried over MgSO4
  6. customthe solvent was removed under reduced pressure
  7. customThe residue was purified by flash column chromatography on silica gel eluting with dichloromethane
  8. customThe product was triturated with ethyl acetate (3 ml)

Sources & evidence

ORD record
ord-deeb46f56a0f4b4e8933bbf2801e5dd5
Source dataset
uspto-grants-2006_11
Patent number
US07141586B2

Reaction notes

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