2,6-Lutidine → Pf-04531083

HRID 1094782Notes

Reaction equation

HRID 1094782 reaction equation
[CH3:1][N:2]1[C:6]([C:7]([OH:9])=O)=[CH:5][CH:4]=[N:3]1.C(Cl)(=O)C(Cl)=O.[Cl:16][C:17]1[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][C:18]=1[C:25]1[C:26]([NH2:32])=[N:27][C:28]([NH2:31])=[CH:29][CH:30]=1.N1C(C)=CC=CC=1C>ClCCl.CN(C)C=O.C(#N)C>[NH2:32][C:26]1[N:27]=[C:28]([NH:31][C:7]([C:6]2[N:2]([CH3:1])[N:3]=[CH:4][CH:5]=2)=[O:9])[CH:29]=[CH:30][C:25]=1[C:18]1[CH:19]=[C:20]([O:23][CH3:24])[CH:21]=[CH:22][C:17]=1[Cl:16]

Participants

8

Reactant 4

HCID 79372,6-LutidineHCID 65578Oxalyl chlorideHCID 6431581-methyl-1H-pyrazole-5-carboxylic acidHCID 575823413-(2-Chloro-5-methoxyphenyl)pyridine-2,6-diamine

Product 1

HCID 57582353Pf-04531083Yield 49.3%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6342AcetonitrileSolvent2×HCID 6344DichloromethaneSolvent

Procedure

To a solution of 1-methyl-1H-pyrazole-5-carboxylic acid (5.28 g, 41.9 mmol) in dichloromethane (55 ml) was added oxalyl chloride (9.14 ml, 104.8 mmol) followed by 3 drops of dimethylformamide. The reaction was stirred at room temperature for 18 hours before concentration in vacuo. The residue was dissolved in acetonitrile (42 ml) and added dropwise to a cooled solution of 3-(2-chloro-5-methoxyphenyl)pyridine-2,6-diamine (preparation 1, 9.5 g, 38 mmol) and lutidine (6.6 ml, 57.1 mmol) in acetonitrile (650 ml). The reaction was allowed to warm to room temperature and stirred under nitrogen for 2 hours. The reaction was quenched by the addition of water (300 ml) and concentrated to low volume in vacuo. The aqueous residue was washed with dichloromethane (2×300 ml), dried (MgSO4) and concentrated in vacuo. The residue was purified by silica gel column chromatography eluting with ethylacetate:heptane 1:4 to furnish a solid. This was recrystallised from toluene (100 ml) to afford 6.7 g of the title product.

Workup

  1. temperatureto warm to room temperature
  2. stirringstirred under nitrogen for 2 hours
  3. customThe reaction was quenched by the addition of water (300 ml)
  4. concentrationconcentrated to low volume in vacuo
  5. washThe aqueous residue was washed with dichloromethane (2×300 ml)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by silica gel column chromatography
  9. washeluting with ethylacetate:heptane 1:4
  10. customto furnish a solid
  11. customThis was recrystallised from toluene (100 ml)

Sources & evidence

ORD record
ord-53244c5d42a54dae8bcd35355a36c724
Source dataset
uspto-grants-2012_03
Patent number
US08134007B2

Reaction notes

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