4-Methylmorpholine → HCID 23114700, compound

HRID 2080421Notes

Reaction equation

HRID 2080421 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([CH:11]([C:21]2[CH:26]=[C:25]([F:27])[CH:24]=[CH:23][C:22]=2[F:28])[C:12]2[N:17]=[CH:16][C:15]([C:18]([OH:20])=O)=[CH:14][CH:13]=2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.S(Cl)(Cl)=O.CN1CCOCC1.[CH3:40][CH:41]1[CH2:46][CH2:45][CH:44]([NH2:47])[CH2:43][CH2:42]1>CN(C)C=O.ClCCl.CCCCCC>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([CH:11]([C:21]2[CH:26]=[C:25]([F:27])[CH:24]=[CH:23][C:22]=2[F:28])[C:12]2[CH:13]=[CH:14][C:15]([C:18]([NH:47][CH:44]3[CH2:45][CH2:46][CH:41]([CH3:40])[CH2:42][CH2:43]3)=[O:20])=[CH:16][N:17]=2)(=[O:10])=[O:9])=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 79724-MethylmorpholineHCID 24386Thionyl ChlorideHCID 806044-MethylcyclohexylamineHCID 23114724[6-[(4-Chlorophenylsulfonyl)(2,5-difluorophenyl)methyl]pyridin-3-yl]carboxylic acid

Product 1

HCID 23114700HCID 23114700, compoundYield 57.2%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent3×HCID 8058HexaneSolvent

Procedure

To a dichloromethane (4 ml) suspension of the [6-[(4-chlorophenylsulfonyl)(2,5-difluorophenyl)methyl]pyridin-3-yl]carboxylic acid (100 mg, 0.236 mmol) obtained in Example 50 were added thionyl chloride (1.00 ml) and N,N-dimethylformamide (one drop). The resulting mixture was stirred at room temperature for 6 hours. The reaction mixture was concentrated to dryness and the residue thus obtained was dissolved in dichloromethane (6 ml). To the resulting solution were added N-methylmorpholine (51.8 μl, 0.472 mmol) and 4-methylcyclohexylamine (37.4 μl, 0.283 mmol). The resulting mixture was stirred at room temperature for 18 hours, followed by dilution with dichloromethane. The diluted mixture was washed sequentially with 1N hydrochloric acid, water and brine, dried over magnesium sulfate and concentrated. The residue thus obtained was subjected to flash silica gel column chromatography. The fraction obtained from the hexane:ethyl acetate=3:1 eluate was concentrated to give a white solid. The solid thus obtained was recrystallized from ethyl acetate-hexane to give the title compound (70.3 mg, 0.135 mmol, 57%) as a white powder.

Workup

  1. concentrationThe reaction mixture was concentrated to dryness
  2. customthe residue thus obtained
  3. stirringThe resulting mixture was stirred at room temperature for 18 hours
  4. washThe diluted mixture was washed sequentially with 1N hydrochloric acid, water and brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated
  7. customThe residue thus obtained
  8. concentrationethyl acetate=3:1 eluate was concentrated
  9. customto give a white solid
  10. customThe solid thus obtained
  11. customwas recrystallized from ethyl acetate-hexane

Sources & evidence

ORD record
ord-c004c11239b146bc9ac592215896f2df
Source dataset
uspto-grants-2011_04
Patent number
US07932271B2

Reaction notes

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