Triethylamine → HCID 86674652, compound

HRID 245707

Reaction equation

HRID 245707 reaction equation
Cl.[F:2][C:3]([F:14])([F:13])[C:4]1[N:8]2[CH2:9][CH2:10][NH:11][CH2:12][C:7]2=[N:6][N:5]=1.C(N(CC)C(C)C)(C)C.Cl[C:25](OC(Cl)(Cl)Cl)=[O:26].Cl.[NH2:33][CH2:34][C:35]1[C:40]([Cl:41])=[N:39][CH:38]=[CH:37][N:36]=1.C(N(CC)CC)C>O1CCCC1.ClCCl>[Cl:41][C:40]1[C:35]([CH2:34][NH:33][C:25]([N:11]2[CH2:10][CH2:9][N:8]3[C:4]([C:3]([F:13])([F:2])[F:14])=[N:5][N:6]=[C:7]3[CH2:12]2)=[O:26])=[N:36][CH:37]=[CH:38][N:39]=1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 10426DiphosgeneHCID 81531DiisopropylethylamineHCID 119613713-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochlorideHCID 42614233(3-Chloropyrazin-2-yl)methanamine hydrochloride

Product 1

HCID 86674652HCID 86674652, compoundYield 88.8%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A suspension of 3-(trifluoromethyl)-1,2,4-triazolo[4,3-a]piperazine hydrochloride (10.94 mmol, 2.5 g) in a mixture of tetrahydrofuran (50 ml) and N,N-diisopropylethylamine (32.8 mmol, 5.42 ml) was added to trichloromethyl chloroformate (13.12 mmol, 1.583 ml) in tetrahydrofuran (50 ml) at 0° C. After one hour at 0° C. the reaction mixture was filtered over decalite and the filter washed with tetrahydrofuran. Then the filtrate was concentrated in vacuo. The residue (4.52 g, crude) was added to 2-aminomethyl-3-chloropyrazine hydrochloride (content 77%; 8.43 mmol, 1.97 g) in a mixture of dichloromethane (50 ml) and triethylamine (25.3 mmol, 3.52 ml) and the reaction mixture was stirred over night at room temperature. Then the reaction mixture was filtered over decalite and the filter washed with dichloromethane. The filtrate was washed with water. The aqueous layer was extracted three times with dichloromethane. The combined organic extracts were washed with brine, dried (sodium sulfate) and concentrated in vacuo. The crude product was purification by column chromatography (silica gel; dichloromethane with gradient 0 to 10% methanol) to give N-((3-chloropyrazin-2-yl)methyl)-3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazine-7(8H)-carboxamide (2.707 g).

Workup

  1. filtrationAfter one hour at 0° C. the reaction mixture was filtered over decalite
  2. washthe filter washed with tetrahydrofuran
  3. concentrationThen the filtrate was concentrated in vacuo
  4. filtrationThen the reaction mixture was filtered over decalite
  5. washthe filter washed with dichloromethane
  6. washThe filtrate was washed with water
  7. extractionThe aqueous layer was extracted three times with dichloromethane
  8. washThe combined organic extracts were washed with brine
  9. dry with materialdried (sodium sulfate)
  10. concentrationconcentrated in vacuo
  11. custompurification by column chromatography (silica gel; dichloromethane with gradient 0 to 10% methanol)

Sources & evidence

ORD record
ord-e000ffce51994684a1308de78569fd27
Source dataset
uspto-grants-2014_02
Patent number
US08658794B2

Linked notes

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