4-Methylmorpholine → 1-[[5-[(2,5-Difluorophenyl)[(4-fluorophenyl)sulfonyl]methyl]-4-methylpyridin-2-yl]carbonyl]azetidin-3-ol

HRID 1641734Notes

Reaction equation

HRID 1641734 reaction equation
C1(C(C2C=CC=CC=2)[N:8]2[CH2:11][CH:10]([OH:12])[CH2:9]2)C=CC=CC=1.[H][H].[F:21][C:22]1[CH:27]=[CH:26][C:25]([F:28])=[CH:24][C:23]=1[CH:29]([S:40]([C:43]1[CH:48]=[CH:47][C:46]([F:49])=[CH:45][CH:44]=1)(=[O:42])=[O:41])[C:30]1[C:31]([CH3:39])=[CH:32][C:33]([C:36]([OH:38])=O)=[N:34][CH:35]=1.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.CN1CCOCC1>C(O)C.[C].[Pd]>[F:21][C:22]1[CH:27]=[CH:26][C:25]([F:28])=[CH:24][C:23]=1[CH:29]([S:40]([C:43]1[CH:44]=[CH:45][C:46]([F:49])=[CH:47][CH:48]=1)(=[O:41])=[O:42])[C:30]1[C:31]([CH3:39])=[CH:32][C:33]([C:36]([N:8]2[CH2:11][CH:10]([OH:12])[CH2:9]2)=[O:38])=[N:34][CH:35]=1

Participants

9

Reactant 6

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 3304481-(Diphenylmethyl)azetidin-3-olHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 577364395-[(2,5-Difluorophenyl)[(4-fluorophenyl)sulfonyl]methyl]-4-methylpyridine-2-carboxylic acidHCID 178418361HCID 178418361, compound

Product 1

HCID 577364871-[[5-[(2,5-Difluorophenyl)[(4-fluorophenyl)sulfonyl]methyl]-4-methylpyridin-2-yl]carbonyl]azetidin-3-olYield 56.3%

Reagents, catalysts & solvents 2

HCID 178418390HCID 178418390, compoundCatalystHCID 702EthanolSolvent

Procedure

To a solution of 1-(diphenylmethyl)azetidin-3-ol (230 mg, 0.961 mmol) in ethanol (10 ml), palladium-carbon (50 mg) was added, and the mixture was stirred for 1.5 hours in a hydrogen atmosphere. The reaction suspension was filtered, and then the filtrate was concentrated under reduced pressure. The resulting concentration residue was dissolved in methylene chloride (10 ml), and 5-[(2,5-difluorophenyl)[(4-fluorophenyl)sulfonyl]methyl]-4-methylpyridine-2-carboxylic acid (113 mg, 0.268 mmol) obtained in Example 12, 1-hydroxybenzotriazole (36 mg, 0.268 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (62 mg, 0.322 mmol) and 4-methylmorpholine (35 μl, 0.322 mmol) were added. The mixture was stirred for 4 days at room temperature. The reaction solution was concentrated under reduced pressure, ethyl acetate was added, and the mixture was washed sequentially with saturated aqueous sodium hydrogencarbonate and saturated brine. The organic layer was dried over anhydrous sodium sulfate and filtered, and then the filtrate was concentrated under reduced pressure. The resulting concentration residue was subjected to silica gel column chromatography, and the fraction obtained from an elution with methanol:methylene chloride (=1:40) was concentrated under reduced pressure, to obtain a solid. The obtained solid was washed with ethanol, and then was collected by filtration to obtain the title compound (72 mg, 0.151 mmol, 56%) as a white powder.

Workup

  1. filtrationThe reaction suspension was filtered
  2. concentrationthe filtrate was concentrated under reduced pressure
  3. concentrationThe resulting concentration residue
  4. dissolutionwas dissolved in methylene chloride (10 ml)
  5. concentrationThe reaction solution was concentrated under reduced pressure, ethyl acetate
  6. additionwas added
  7. washthe mixture was washed sequentially with saturated aqueous sodium hydrogencarbonate and saturated brine
  8. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. concentrationthe filtrate was concentrated under reduced pressure
  11. concentrationThe resulting concentration residue
  12. customthe fraction obtained from an elution with methanol
  13. concentrationmethylene chloride (=1:40) was concentrated under reduced pressure
  14. customto obtain a solid
  15. washThe obtained solid was washed with ethanol
  16. filtrationwas collected by filtration

Sources & evidence

ORD record
ord-403e08fdf0fe4ca688d230c606d7d302
Source dataset
uspto-grants-2012_02
Patent number
US08114886B2

Reaction notes

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