1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → 3-Trifluoromethyl-pyrazine-2-carboxylic acid [1-(5-bromo-3-chloro-pyridin-2-yl)-cyclopropylmethyl]-amide

HRID 578873Notes

Reaction equation

HRID 578873 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.FC(F)(F)C1C(C(O)=O)=NC=CC=1.C1C=C2N=NN(O)C2=CC=1.O.CCN=C=NCCCN(C)C.Cl.[F:50][C:51]([F:62])([F:61])[C:52]1[C:53]([C:58](O)=[O:59])=[N:54][CH:55]=[CH:56][N:57]=1>ClCCl.O.C(N(CC)CC)C>[Br:1][C:2]1[CH:3]=[C:4]([Cl:13])[C:5]([C:8]2([CH2:11][NH:12][C:58]([C:53]3[C:52]([C:51]([F:61])([F:50])[F:62])=[N:57][CH:56]=[CH:55][N:54]=3)=[O:59])[CH2:9][CH2:10]2)=[N:6][CH:7]=1

Participants

9

Reactant 5

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 132338443-(Trifluoromethyl)pyridine-2-carboxylic acidHCID 536308603-(Trifluoromethyl)pyrazine-2-carboxylic acidHCID 89544163(1-(5-Bromo-3-chloropyridin-2-yl)cyclopropyl)methanamine

Product 1

HCID 1317328733-Trifluoromethyl-pyrazine-2-carboxylic acid [1-(5-bromo-3-chloro-pyridin-2-yl)-cyclopropylmethyl]-amideYield 91.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

50 mg of C-[1-(5-bromo-3-chloro-pyridin-2-yl)-cyclopropyl]-methylamine (step 1 of PREPARATION EXAMPLE 2) was dissolved in 0.9 ml of dichloromethane and 0.085 ml of triethylamine was added at ambient temperature. Then 383 mg of 3-(trifluoromethyl)pyridine-2-carboxylic acid, 54 mg of HOBT hydrate, 76 mg of EDCI.HCl and 37 mg of 3-trifluoromethyl-pyrazine-2-carboxylic acid were added sequentially. The reaction mixture was stirred at ambient temperature for 14 hours and then water was added, the phases were separated and the aqueous phase was extracted with dichloromethane. The organic phases were combined, dried with anhydrous sodium sulphate, filtered and concentrated. Crude material was obtained as a yellow sticky solid, which was purified by flash chromatography on silica gel with cyclohexane/ethyl acetate (1:1) as a solvent. Thus, 76 mg of 3-trifluoromethyl-pyrazine-2-carboxylic acid [1-(5-bromo-3-chloro-pyridin-2-yl)-cyclopropylmethyl]-amide was obtained as a sticky solid. 1H-NMR (CDCl3): 8.80 ppm (s, 1H), 8.75 ppm (s, 1H), 8.65 ppm (s, 1H), 7.95 ppm (s, 1H), 7.70 ppm (m, 1H), 3.72 ppm (d, 2H), 1.18 ppm (m, 4H).

Workup

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

Sources & evidence

ORD record
ord-68fe14f4696346fc9481de14d533d809
Source dataset
uspto-grants-2015_05
Patent number
US09040708B2

Reaction notes

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