Water → N-[1-(5-bromo-3-chloro-pyridin-2-yl)-cyclopropylmethyl]-2,6-difluoro-benzamide

HRID 878461Notes

Reaction equation

HRID 878461 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]1[CH:30]=[CH:29][CH:28]=[C:27]([F:31])[C:23]=1[C:24](Cl)=[O:25].O>ClCCl>[Br:1][C:2]1[CH:3]=[C:4]([Cl:13])[C:5]([C:8]2([CH2:11][NH:12][C:24](=[O:25])[C:23]3[C:22]([F:21])=[CH:30][CH:29]=[CH:28][C:27]=3[F:31])[CH2:9][CH2:10]2)=[N:6][CH:7]=1

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 874382,6-Difluorobenzoyl chlorideHCID 89544163(1-(5-Bromo-3-chloropyridin-2-yl)cyclopropyl)methanamine

Product 1

HCID 89544494N-[1-(5-bromo-3-chloro-pyridin-2-yl)-cyclopropylmethyl]-2,6-difluoro-benzamideYield 84.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

570 mg of C-[1-(5-bromo-3-chloro-pyridin-2-yl)-cyclopropyl]-methylamine (step 3) was dissolved in 8 ml of dichloromethane and cooled to 0° C. 441 mg of triethylamine was added, followed by dropwise addition of a solution of 385 mg of 2,6-difluorobenzoyl chloride in 2 ml of dichloromethane. The reaction mixture was stirred at ambient temperature for 1 hour. Water was added and the reaction mixture was extracted twice with dichloromethane. The organic phase was dried over sodium sulfate, filtered and concentrated. 1095 mg of crude material was obtained as a pale brown sticky oil. This residue was purified by chromatography on silica gel with cyclohexane/ethyl acetate (3:1) as a eluent. Thus, 742 mg of N-[1-(5-bromo-3-chloro-pyridin-2-yl)-cyclopropylmethyl]-2,6-difluoro-benzamide was obtained as a yellow sticky oil. 1H-NMR (CDCl3): 8.47 ppm (s, 1H), 7.86 ppm (s, 1H), 7.33 ppm (m, 1H), 6.90 ppm (t, 2H), 6.30 ppm (s, 1H, broad), 3.71 ppm (d, 2H), 1.09 ppm (m, 4H).

Workup

  1. extractionthe reaction mixture was extracted twice with dichloromethane
  2. dry with materialThe organic phase was dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. custom1095 mg of crude material was obtained as a pale brown sticky oil
  6. customThis residue was purified by chromatography on silica gel with cyclohexane/ethyl acetate (3:1) as a eluent

Sources & evidence

ORD record
ord-81d53c1efa0c4d398a22c854ae5a6395
Source dataset
uspto-grants-2015_03
Patent number
US08987465B2

Reaction notes

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