4-Methylmorpholine → HCID 57736419, compound

HRID 1641722Notes

Reaction equation

HRID 1641722 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.[NH2:30][CH:31]([CH2:34][OH:35])[CH2:32][OH:33].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:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=1)(=[O:21])=[O:22])[C:10]1[C:11]([CH3:19])=[CH:12][C:13]([C:16]([NH:30][CH:31]([CH2:34][OH:35])[CH2:32][OH:33])=[O:17])=[N:14][CH:15]=1

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 68294SerinolHCID 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 57736419HCID 57736419, compoundYield 74.2%

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 (93 mg, 0.221 mmol) obtained in Example 12 in methylene chloride (3 ml), 2-amino-1,3-propanediol (24 mg, 0.265 mmol), 1-hydroxybenzotriazole (30 mg, 0.221 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (51 mg, 0.265 mmol) and 4-methylmorpholine (29 μl, 0.265 mmol) were added, and the resulting mixture was stirred for 17 hours at room temperature. Ethyl acetate was added to the reaction solution, and the mixture was washed sequentially with a saturated solution of sodium hydrogencarbonate and saturated brine. The organic layer was dried over anhydrous sodium sulfate and filtered, and 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 (=1:20) was concentrated under reduced pressure. Ethylacetate-hexane was added to the resulting concentration residue, and the solid thus precipitated was collected by filtration, to obtain the title compound (81 mg, 0.164 mmol, 74%) as a white powder.

Workup

  1. washthe mixture was washed sequentially with a saturated solution of 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 (=1:20) was concentrated under reduced pressure
  8. additionEthylacetate-hexane was added to the resulting concentration residue
  9. customthe solid thus precipitated
  10. filtrationwas collected by filtration

Sources & evidence

ORD record
ord-631b9ad5995341bdb6714d8be100d21b
Source dataset
uspto-grants-2012_02
Patent number
US08114886B2

Reaction notes

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