4-Methylmorpholine → HCID 11999689, compound

HRID 1641691Notes

Reaction equation

HRID 1641691 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[CH:9]([S:20][C:21]1[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=1)[C:10]1[C:11]([CH3:19])=[CH:12][C:13]([C:16](O)=[O:17])=[N:14][CH:15]=1.Cl.[CH3:29][NH:30][CH3:31].[OH:32]N1C2C=CC=CC=2N=N1.CN1CCOCC1.Cl.C(N=C=NCCCN(C)C)C.ClC1C=CC=C(C(OO)=O)C=1>C(Cl)Cl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[CH:9]([S:20]([C:21]1[CH:22]=[CH:23][C:24]([F:27])=[CH:25][CH:26]=1)=[O:32])[C:10]1[C:11]([CH3:19])=[CH:12][C:13]([C:16]([N:30]([CH3:31])[CH3:29])=[O:17])=[N:14][CH:15]=1

Participants

8

Reactant 6

HCID 79724-MethylmorpholineHCID 10473Dimethylamine, hydrochlorideHCID 70297m-Chloroperbenzoic acidHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 57736444HCID 57736444, compound

Product 1

HCID 11999689HCID 11999689, compoundYield 23%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 5-[(2,5-difluorophenyl)[(4-fluorophenyl)thio]methyl]-4-meth ylpyridine-2-carboxylic acid (307 mg, 0.79 mmol) obtained in Example 20 in methylene chloride (8 ml), dimethylamine hydrochloride (130 mg, 1.58 mmol), 1-hydroxybenzotriazole (213 mg, 1.58 mmol), 4-methylmorpholine (0.347 ml, 3.15 mmol), and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (302 mg, 1.58 mmol) were added at room temperature. After stirring for 17 hours at room temperature, the reaction mixture was washed with saturated aqueous sodium hydrogencarbonate. The organic layer was dried over anhydrous sodium sulfate and filtered, then the filtrate was concentrated under reduced pressure, and the resulting residue was subjected to flash silica gel chromatography. The fraction obtained from an elution with hexane:ethyl acetate=1:1 was concentrated under reduced pressure. To a solution the resulting residue in methylene chloride (5 ml), 3-chloroperbenzoic acid (112 mg, 0.42 mmol) was added at 0° C. After stirring for 1 hour at room temperature, the reaction mixture was washed with 1 N aqueous sodium hydroxide. The organic layer was dried over anhydrous sodium sulfate and filtered, then the filtrate was concentrated under reduced pressure, and the resulting residue was subjected to preparative thin-layer chromatography (developed with hexane:ethyl acetate=1:2, eluted with methylene chloride:methanol=4:1). The obtained fraction was concentrated under reduced pressure, and the resulting residue was washed with a mixed solvent of ethanol and hexane, and was collected by filtration, to obtain the title compound (78 mg, 0.18 mmol, 23%) as a white solid.

Workup

  1. washthe reaction mixture was washed with saturated aqueous sodium hydrogencarbonate
  2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. customThe fraction obtained from an elution with hexane
  6. concentrationethyl acetate=1:1 was concentrated under reduced pressure
  7. stirringAfter stirring for 1 hour at room temperature
  8. washthe reaction mixture was washed with 1 N aqueous sodium hydroxide
  9. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  10. filtrationfiltered
  11. concentrationthe filtrate was concentrated under reduced pressure
  12. washthin-layer chromatography (developed with hexane:ethyl acetate=1:2, eluted with methylene chloride:methanol=4:1)
  13. concentrationThe obtained fraction was concentrated under reduced pressure
  14. washthe resulting residue was washed with a mixed solvent of ethanol and hexane
  15. filtrationwas collected by filtration

Sources & evidence

ORD record
ord-caef72af8ed94a41875396998d9b8cfa
Source dataset
uspto-grants-2012_02
Patent number
US08114886B2

Reaction notes

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