Water → 6-chloro-N-[(1S)-1-(3,4-difluorophenyl)ethyl]pyrazin-2-amine

HRID 16142

Reaction equation

HRID 16142 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C@@H:9]([NH2:11])[CH3:10])[CH:5]=[CH:6][C:7]=1[F:8].[Cl:12][C:13]1[CH:18]=[N:17][CH:16]=[C:15](Cl)[N:14]=1.C(=O)([O-])[O-].[K+].[K+].O>O1CCOCC1>[Cl:12][C:13]1[N:14]=[C:15]([NH:11][C@H:9]([C:4]2[CH:5]=[CH:6][C:7]([F:8])=[C:2]([F:1])[CH:3]=2)[CH3:10])[CH:16]=[N:17][CH:18]=1

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 785042,6-DichloropyrazineHCID 7016601(S)-1-(3,4-Difluorophenyl)ethanamine

Product 1

HCID 588699336-chloro-N-[(1S)-1-(3,4-difluorophenyl)ethyl]pyrazin-2-amineYield 35.1%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

(1S)-1-(3,4-Difluorophenyl)ethanamine (977 mg, 6.2 mmol) and 2,6-dichloropyrazine (1.236 g, 8.3 mmol, 1.3 eq) was dissolved in dioxane (5 mL) and potassium carbonate (1.73 g, 2.0 eq) added to the solution. The mixture was then heated at reflux (110° C.) under a nitrogen atmosphere for 65 hours. The crude reaction mixture was then poured onto cold water (30 mL) and extracted with diethyl ether (3×30 mL). The combined organic extracts were concentrated and subjected to flashmaster chromatography (20 g silica cartridge (8:2 petroleum spirits:ethyl acetate, followed by ethyl acetate flush) to afford the desired pyrazine-adduct as an off-white solid (587 mg, 35%).

Workup

  1. temperatureThe mixture was then heated
  2. customThe crude reaction mixture
  3. extractionextracted with diethyl ether (3×30 mL)
  4. concentrationThe combined organic extracts were concentrated
  5. custom20 g silica cartridge (8:2 petroleum spirits:ethyl acetate, followed by ethyl acetate flush)

Sources & evidence

ORD record
ord-6509b31877f84ef2b22f7be7512ab378
Source dataset
uspto-grants-2010_06
Patent number
US07737143B2

Linked notes

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