4-Methylmorpholine → 4-[[5-[(2,5-Difluorophenyl)[(4-fluorophenyl)sulfonyl]methyl]-4-methylpyridin-2-yl]carbonyl]morpholine

HRID 1641724Notes

Reaction equation

HRID 1641724 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](O)=[O:17])=[N:14][CH:15]=1.[NH:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.CN1CCOCC1>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: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]([N:30]2[CH2:35][CH2:34][O:33][CH2:32][CH2:31]2)=[O:17])=[N:14][CH:15]=1

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 8083MorpholineHCID 757711-HydroxybenzotriazoleHCID 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 577365174-[[5-[(2,5-Difluorophenyl)[(4-fluorophenyl)sulfonyl]methyl]-4-methylpyridin-2-yl]carbonyl]morpholineYield 68.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 5-[(2,5-difluorophenyl)[(4-fluorophenyl)sulfonyl]methyl]-4-methylpyridine-2-carboxylic acid (119 mg, 0.282 mmol) obtained in Example 12 in methylene chloride (3 ml), morpholine (30 μl, 0.339 mmol), 1-hydroxybenzotriazole (38 mg, 0.282 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride mg, 0.339 mmol) and 4-methylmorpholine (37 μl, 0.339 mmol) were added. The reaction solution was stirred for 5 days at room temperature, and was concentrated under reduced pressure. The resulting concentration residue was subjected to silica gel column chromatography, and the fraction obtained from an elution with 65% ethyl acetate/hexane 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 (94 mg, 0.192 mmol, 68%) as a white powder.

Workup

  1. concentrationwas concentrated under reduced pressure
  2. concentrationThe resulting concentration residue
  3. customthe fraction obtained from an elution with 65% ethyl acetate/hexane
  4. concentrationwas concentrated under reduced pressure
  5. additionEthyl acetate-hexane was added to the resulting concentration residue
  6. customthe solid thus precipitated
  7. filtrationwas collected by filtration

Sources & evidence

ORD record
ord-2102f31d8fb9422bb4a3629b6126cb99
Source dataset
uspto-grants-2012_02
Patent number
US08114886B2

Reaction notes

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