4-Methylmorpholine → HCID 57736539, compound

HRID 1641723Notes

Reaction equation

HRID 1641723 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:23]1[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=1)(=[O:22])=[O:21])[C:10]1[C:11]([CH3:19])=[CH:12][C:13]([C:16]([OH:18])=O)=[N:14][CH:15]=1.[OH:30][CH:31]1[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]1.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.CN1CCOCC1>C(Cl)Cl.C(OCC)(=O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[CH:9]([S:20]([C:23]1[CH:24]=[CH:25][C:26]([F:29])=[CH:27][CH:28]=1)(=[O:22])=[O:21])[C:10]1[C:11]([CH3:19])=[CH:12][C:13]([C:16]([N:34]2[CH2:35][CH2:36][CH:31]([OH:30])[CH2:32][CH2:33]2)=[O:18])=[N:14][CH:15]=1

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 79341Piperidin-4-olHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 577364395-[(2,5-Difluorophenyl)[(4-fluorophenyl)sulfonyl]methyl]-4-methylpyridine-2-carboxylic acid

Product 1

HCID 57736539HCID 57736539, compoundYield 68%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 5-[(2,5-difluorophenyl)[(4-fluorophenyl)sulfonyl]methyl]-4-methylpyridine-2-carboxylic acid (94 mg, 0.223 mmol) obtained in Example 12 in methylene chloride (3 ml), 4-hydroxypiperidine (27 mg, 0.268 mmol), 1-hydroxybenzotriazole (30 mg, 0.223 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride mg, 0.268 mmol) and 4-methylmorpholine (29 μl, 0.268 mmol) were added, and the resulting mixture was stirred for 18 hours at room temperature. Ethyl acetate was added to the reaction solution, and the mixture was washed sequentially with an 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 (=1:30) was concentrated under reduced pressure. Ethyl acetate-hexane was added to the resulting concentration residue, and the solid thus precipitated was collected by filtration, to obtain the title compound (76 mg, 0.151 mmol, 68%) as a white powder.

Workup

  1. washthe mixture was washed sequentially with an aqueous sodium hydrogencarbonate and saturated brine
  2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. concentrationThe resulting concentration residue
  6. customthe fraction obtained from an elution with methanol
  7. concentrationmethylene chloride (=1:30) was concentrated under reduced pressure
  8. additionEthyl acetate-hexane was added to the resulting concentration residue
  9. customthe solid thus precipitated
  10. filtrationwas collected by filtration

Sources & evidence

ORD record
ord-7878cd2200134ffb800a22fb12cda98b
Source dataset
uspto-grants-2012_02
Patent number
US08114886B2

Reaction notes

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