Dimethylformamide → Soticlestat

HRID 60611Notes

Reaction equation

HRID 60611 reaction equation
[CH2:1]([C:8]1([OH:23])[CH2:13][CH2:12][N:11]([C:14]([C:16]2[C:17](Cl)=[N:18][CH:19]=[CH:20][CH:21]=2)=[O:15])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N:24]1[CH:29]=[CH:28][C:27](B(O)O)=[CH:26][CH:25]=1.C(=O)([O-])[O-].[Na+].[Na+].CN(C=O)C>[Cl-].[Na+].O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[CH2:1]([C:8]1([OH:23])[CH2:13][CH2:12][N:11]([C:14]([C:16]2[C:17]([C:27]3[CH:28]=[CH:29][N:24]=[CH:25][CH:26]=3)=[N:18][CH:19]=[CH:20][CH:21]=2)=[O:15])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 2734379(Pyridin-4-yl)boronic acidHCID 86680867(4-Benzyl-4-hydroxypiperidin-1-yl)(2-chloropyridin-3-yl)methanone

Product 1

HCID 73437845SoticlestatYield 60.2%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of (4-benzyl-4-hydroxypiperidin-1-yl) (2-chloropyridin-3-yl)methanone (5.0 g), tetrakis(triphenylphosphine)palladium(0) (0.87 g), pyridine-4-boronic acid (2.2 g), sodium carbonate (4.8 g), DMF (50 mL) and water (10 ml) was stirred overnight at 100° C. under a nitrogen atmosphere. To the reaction mixture was added saturated brine, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (NH, ethyl acetate/hexane) to give the title compound (3.4 g). The compound was crystallized from ethyl acetate/heptane to give the title compound as crystals.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe extract was washed with saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (NH, ethyl acetate/hexane)

Sources & evidence

ORD record
ord-cd6610d24106429e97200c99e6a31796
Source dataset
uspto-grants-2016_09
Patent number
US09440990B2

Reaction notes

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