Diisopropylethylamine → 6'-Chloro-2-methyl-[3,4']bipyridinyl-3'-carboxylic acid (3,5-bis-trifluoromethyl-benzyl)-methyl-amide

HRID 347687Notes

Reaction equation

HRID 347687 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][C:5]([C:8]([OH:10])=O)=[C:4]([C:11]2[C:12]([CH3:17])=[N:13][CH:14]=[CH:15][CH:16]=2)[CH:3]=1.[F:18][C:19]([F:34])([F:33])[C:20]1[CH:21]=[C:22]([CH:26]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:28]=1)[CH2:23][NH:24][CH3:25].C(N(CC)C(C)C)(C)C>ClCCl.CN(C=O)C.C(OCC)(=O)C>[F:18][C:19]([F:33])([F:34])[C:20]1[CH:21]=[C:22]([CH:26]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:28]=1)[CH2:23][N:24]([CH3:25])[C:8]([C:5]1[CH:6]=[N:7][C:2]([Cl:1])=[CH:3][C:4]=1[C:11]1[C:12]([CH3:17])=[N:13][CH:14]=[CH:15][CH:16]=1)=[O:10]

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 10956204{[3,5-Bis(trifluoromethyl)phenyl]methyl}(methyl)amineHCID 21083637HCID 21083637, compound

Product 1

HCID 586945956'-Chloro-2-methyl-[3,4']bipyridinyl-3'-carboxylic acid (3,5-bis-trifluoromethyl-benzyl)-methyl-amide

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of 0.10 g (0.40 mmol) 6′-chloro-2-methyl-[3,4′]bipyridinyl-3′-carboxylic acid in 4 ml dicloromethane were added dropwise at 0° C. under argon 0.05 ml (0.6 mmol) oxalyl chloride and one drop of DMF. The reaction mixture was allowed to slowly warm to room temperature. After 1 h the mixture was concentrated in vacuo and redissolved in 2 ml dichloromethane. This solution was added dropwise at 0° C. to a mixture of 0.16 g (0.60 mmol) (3,5-bis-trifluoromethyl-benzyl)-methyl-amine and 0.14 ml (0.80 mmol) N,N-diisopropylethylamine in 2 ml dichloromethane. After 30 min. the reaction mixture was diluted with ethyl acetate and washed with a 1 M aqueous sodium hydroxide solution. The aqueous layer was extracted with ethyl acetate. The combined organic layers were dried over sodium sulfate and concentrated in vacuo to give 0.29 g of crude product. Flash chromatography gave 0.21 g (quant.) of the title compound.

Workup

  1. additionwere added dropwise at 0° C. under argon 0.05 ml (0.6 mmol) oxalyl chloride
  2. concentrationAfter 1 h the mixture was concentrated in vacuo
  3. dissolutionredissolved in 2 ml dichloromethane
  4. washwashed with a 1 M aqueous sodium hydroxide solution
  5. extractionThe aqueous layer was extracted with ethyl acetate
  6. dry with materialThe combined organic layers were dried over sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customto give 0.29 g of crude product

Sources & evidence

ORD record
ord-ce746721c5dc4ef69779611a11a74668
Source dataset
uspto-grants-2007_02
Patent number
US07176205B2

Reaction notes

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