2-Chloronicotinoyl chloride → 2-Chloro-N-(2-chloro-6-methyl-4-trifluoromethyl-3-pyridinyl)-3-pyridinecarboxamide

HRID 53515

Reaction equation

HRID 53515 reaction equation
[NH2:1][C:2]1[C:3]([Cl:13])=[N:4][C:5]([CH3:12])=[CH:6][C:7]=1[C:8]([F:11])([F:10])[F:9].C(NC(C)C)(C)C.[Li].[Cl:22][C:23]1[N:31]=[CH:30][CH:29]=[CH:28][C:24]=1[C:25](Cl)=[O:26]>C1COCC1>[Cl:22][C:23]1[C:24]([C:25]([NH:1][C:2]2[C:3]([Cl:13])=[N:4][C:5]([CH3:12])=[CH:6][C:7]=2[C:8]([F:9])([F:11])[F:10])=[O:26])=[CH:28][CH:29]=[CH:30][N:31]=1

Participants

5

Reactant 3

HCID 27745412-Chloronicotinoyl chlorideHCID 199600793-Amino-2-chloro-6-methyl-4-(trifluoromethyl)pyridineHCID 45051747Lithium diisopropylamine2×

Product 1

HCID 199600722-Chloro-N-(2-chloro-6-methyl-4-trifluoromethyl-3-pyridinyl)-3-pyridinecarboxamideYield 72.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a cooled (-78° C.) solution of 2.1 g of the 3-amino-2-chloro-6-methyl-4-(trifluoromethyl)pyridine in 10 ml of THF was added dropwise over 3 min. 7 ml of lithium diisopropylamine (LDA, 1.5 M in cyclohexane). The mixture was stirred 5 min., and 0.9 g of 2-chloronicotinoyl chloride in 3 ml of THF was added over 1 min. After 5 min. an additional 3 ml of LDA solution was added followed by an additional 0.5 g of the acid chloride in 1 ml of THF. The resulting mixture was stirred 10 min. and then quenched with 100 ml of water. After partitioning with 30 ml of ethyl acetate, the organic phase was extracted with water and the combined aqueous phases extracted with methylene chloride, dried (magnesium sulfate), filtered and evaporated to give the crude product. This was washed with a small amount of ethyl acetate and dried to give 1.3 g of the title compound.

Workup

  1. additionwas added dropwise over 3 min
  2. stirringThe resulting mixture was stirred 10 min.
  3. customquenched with 100 ml of water
  4. customAfter partitioning with 30 ml of ethyl acetate
  5. extractionthe organic phase was extracted with water
  6. extractionthe combined aqueous phases extracted with methylene chloride
  7. dry with materialdried (magnesium sulfate)
  8. filtrationfiltered
  9. customevaporated
  10. customto give the crude product
  11. washThis was washed with a small amount of ethyl acetate
  12. customdried

Sources & evidence

ORD record
ord-94893144c4ff4278af50c60658ae8d42
Source dataset
uspto-grants-1997_04
Patent number
US05620974

Linked notes

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