Triethylamine → HCID 86674652、化合物

HRID 245707

反応式

HRID 245707 の反応式
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

参加物

8

反応物 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

生成物 1

HCID 86674652HCID 86674652、化合物収率 88.8%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran溶媒2 回

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-e000ffce51994684a1308de78569fd27
出典データセット
uspto-grants-2014_02
特許番号
US08658794B2

関連ノート

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