Dimethylformamide → 7-(8-Chloroimidazo[1,5-a]pyrazin-3-yl)-3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyridine

HRID 62477노트

반응식

HRID 62477 반응식
O=P(Cl)(Cl)Cl.[Cl:6][C:7]1[C:8]([CH2:13][NH:14][C:15]([CH:17]2[CH2:22][CH2:21][N:20]3[C:23]([C:26]([F:29])([F:28])[F:27])=[N:24][N:25]=[C:19]3[CH2:18]2)=O)=[N:9][CH:10]=[CH:11][N:12]=1.CN(C=O)C.C([O-])([O-])=O.[Na+].[Na+]>CC#N>[Cl:6][C:7]1[C:8]2[N:9]([C:15]([CH:17]3[CH2:22][CH2:21][N:20]4[C:23]([C:26]([F:29])([F:28])[F:27])=[N:24][N:25]=[C:19]4[CH2:18]3)=[N:14][CH:13]=2)[CH:10]=[CH:11][N:12]=1

참가 물질

6

반응물 4

HCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 24813Phosphorus oxychlorideHCID 90303325N-((3-chloropyrazin-2-yl)methyl)-3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyridine-7-carboxamide

생성물 1

HCID 903040007-(8-Chloroimidazo[1,5-a]pyrazin-3-yl)-3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyridine수율 44.7%

시약·촉매·용매 1

HCID 6342Acetonitrile용매

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온도
70 °C

실험 절차

POCl3 (1.7 g, 11.09 mmol) was added dropwise to a solution of N-((3-chloropyrazin-2-yl)methyl)-3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyridine-7-carboxamide (800 mg, 2.218 mmol) in CH3CN (4.4 mL) at 0° C., then DMF (0.11 mL) was added dropwise for 5 minutes at 0° C. The reaction was heated at 70° C. for overnight The reaction was poured into ice-water, then neutralized with aq. Na2CO3 to adjust to pH=8. The resulting mixture was extracted with DCM and the combined organic layer was washed with water, brine and dried over anhydrous Na2SO4. The organic layer was concentrated in vacuo and the residue was purified by silica gel column chromatography (DCM/THF=100/20) to afford 7-(8-chloroimidazo[1,5-a]pyrazin-3-yl)-3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyridine (0.34 g, yield 44%).

후처리

  1. extractionThe resulting mixture was extracted with DCM
  2. washthe combined organic layer was washed with water, brine
  3. dry with materialdried over anhydrous Na2SO4
  4. concentrationThe organic layer was concentrated in vacuo
  5. customthe residue was purified by silica gel column chromatography (DCM/THF=100/20)

출처 및 근거

ORD 기록
ord-10baf883f2284b12ab50ea83528e820f
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09446130B2

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