Water → N-[[1-(5-bromo-3-chloro-2-pyridyl)cyclopropyl]methyl]-3-(trifluoromethyl)pyridine-2-carboxamide

HRID 578865Notes

Reaction equation

HRID 578865 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([Cl:13])[C:5]([C:8]2([CH2:11][NH2:12])[CH2:10][CH2:9]2)=[N:6][CH:7]=1.C(N(CC)CC)C.[F:21][C:22]([F:33])([F:32])[C:23]1[C:24]([C:29](Cl)=[O:30])=[N:25][CH:26]=[CH:27][CH:28]=1.O>ClCCl>[Br:1][C:2]1[CH:3]=[C:4]([Cl:13])[C:5]([C:8]2([CH2:11][NH:12][C:29]([C:24]3[C:23]([C:22]([F:33])([F:21])[F:32])=[CH:28][CH:27]=[CH:26][N:25]=3)=[O:30])[CH2:9][CH2:10]2)=[N:6][CH:7]=1

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 450819483-(Trifluoromethyl)pyridine-2-carbonyl chlorideHCID 89544163(1-(5-Bromo-3-chloropyridin-2-yl)cyclopropyl)methanamine

Product 1

HCID 71558839N-[[1-(5-bromo-3-chloro-2-pyridyl)cyclopropyl]methyl]-3-(trifluoromethyl)pyridine-2-carboxamideYield 96.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

350 mg of C-[1-(5-bromo-3-chloro-pyridin-2-yl)-cyclopropyl]-methylamine (step 3 of PREPARATION EXAMPLE 3) was dissolved in 7 ml of dichloromethane and 0.37 ml of triethylamine was added at ambient temperature. Then a solution of 308 mg 3-(trifluoromethyl)pyridine-2-carbonyl chloride (1.10 eq, 1.47 mmol, 0.) in 3 ml of dichloromethane was added dropwise. The reaction mixture was stirred at ambient temperature for 14 hours, then water was added, the phases were separated and the water phase was extracted with dichloromethane. The organic phase was dried with anhydrous sodium sulfate, filtered and concentrated. Crude material was obtained as a brown sticky solid, which was purified by flash chromatography on silica gel with cyclohexane/ethyl acetate (2:1) as a solvent. Thus, 560 mg of N-[[1-(5-bromo-3-chloro-2-pyridyl)cyclopropyl]methyl]-3-(trifluoromethyl)pyridine-2-carboxamide was obtained as a sticky solid. 1H-NMR (CDCl3): 8.70 ppm (d, 1H), 8.45 ppm (d, 1H), 8.12 ppm (d, 1H), 7.90 ppm (s, 1H, broad), 7.83 ppm (d, 1H), 7.52 ppm (m, 1H), 3.73 ppm (d, 2H), 1.10 ppm (m, 4H).

Workup

  1. customthe phases were separated
  2. extractionthe water phase was extracted with dichloromethane
  3. dry with materialThe organic phase was dried with anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customCrude material was obtained as a brown sticky solid, which
  7. customwas purified by flash chromatography on silica gel with cyclohexane/ethyl acetate (2:1) as a solvent

Sources & evidence

ORD record
ord-d443e200b3db493fb450d122ac21dec7
Source dataset
uspto-grants-2015_05
Patent number
US09040708B2

Reaction notes

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