p-Toluenesulfonic acid monohydrate → HCID 68006328, compound

HRID 1026583Notes

Reaction equation

HRID 1026583 reaction equation
[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][C:7]([CH3:47])([CH3:46])[C:8](=[O:45])[N:9]2[CH:12]2[CH2:17][CH2:16][N:15]([C:18]([C:20]3[CH:25]=[CH:24][C:23]([C:26]4[CH:31]=[C:30]([F:32])[CH:29]=[CH:28][C:27]=4[O:33][CH2:34][CH2:35][CH2:36][O:37]C4CCCCO4)=[CH:22][C:21]=3[F:44])=[O:19])[CH2:14][CH2:13]2)=[N:4][CH:3]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CO>[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][C:7]([CH3:47])([CH3:46])[C:8](=[O:45])[N:9]2[CH:12]2[CH2:17][CH2:16][N:15]([C:18]([C:20]3[CH:25]=[CH:24][C:23]([C:26]4[CH:31]=[C:30]([F:32])[CH:29]=[CH:28][C:27]=4[O:33][CH2:34][CH2:35][CH2:36][OH:37])=[CH:22][C:21]=3[F:44])=[O:19])[CH2:14][CH2:13]2)=[N:4][CH:3]=1

Participants

4

Reactant 2

HCID 521998p-Toluenesulfonic acid monohydrateHCID 68006169HCID 68006169, compound

Product 1

HCID 68006328HCID 68006328, compoundYield 88.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a methanol solution (10 ml) of 7-chloro-1-[1-({3,5′-difluoro-2′-[3-(tetrahydro-2H-pyran-2-yloxy)propoxy]biphenyl-4-yl}carbonyl)piperidin-4-yl]-3,3-dimethyl-3,4-dihydro-1,5-naphthyridin-2(1H)-one (300 mg) was added at room temperature p-toluenesulfonic acid monohydrate (8.7 mg), followed by stirring for 4 hours. After the reaction solution was concentrated under reduced pressure, a saturated aqueous sodium hydrogen carbonate solution and dichloromethane were added, and the solution was separated. The organic layer was washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to afford 7-chloro-1-(1-{[3,5′-difluoro-2′-(3-hydroxypropoxy)biphenyl-4-yl]carbonyl}piperidin-4-yl)-3,3-dimethyl-3,4-dihydro-1,5-naphthyridin-2(1H)-one (231 mg).

Workup

  1. concentrationAfter the reaction solution was concentrated under reduced pressure
  2. additiona saturated aqueous sodium hydrogen carbonate solution and dichloromethane were added
  3. customthe solution was separated
  4. washThe organic layer was washed with saturated sodium chloride solution
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-62be06fc03634ef2bb1b60b8676282cf
Source dataset
uspto-grants-2014_05
Patent number
US08729095B2

Reaction notes

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