Dimethylformamide → 8-chloro-3-(1-methyl-4,5,6,7-tetrahydro-1H-indazol-4-yl)imidazo[1,5-a]pyrazine

HRID 62445노트

반응식

HRID 62445 반응식
[Cl:1][C:2]1[C:3]([CH2:8][NH:9][C:10]([CH:12]2[CH2:20][CH2:19][CH2:18][C:17]3[N:16]([CH3:21])[N:15]=[CH:14][C:13]2=3)=O)=[N:4][CH:5]=[CH:6][N:7]=1.O=P(Cl)(Cl)Cl.CN(C=O)C>CC#N>[Cl:1][C:2]1[C:3]2[N:4]([C:10]([CH:12]3[CH2:20][CH2:19][CH2:18][C:17]4[N:16]([CH3:21])[N:15]=[CH:14][C:13]3=4)=[N:9][CH:8]=2)[CH:5]=[CH:6][N:7]=1

참가 물질

5

반응물 3

HCID 6228DimethylformamideHCID 24813Phosphorus oxychlorideHCID 90303938N-((3-chloropyrazin-2-yl)methyl)-1-methyl-4,5,6,7-tetrahydro-1H-indazole-4-carboxamide

생성물 1

HCID 903040078-chloro-3-(1-methyl-4,5,6,7-tetrahydro-1H-indazol-4-yl)imidazo[1,5-a]pyrazine수율 70.9%

시약·촉매·용매 1

HCID 6342Acetonitrile용매

반응 조건

온도
60 °C

실험 절차

To a solution of N-((3-chloropyrazin-2-yl)methyl)-1-methyl-4,5,6,7-tetrahydro-1H-indazole-4-carboxamide (1.5 g, 4.9 mmol) in MeCN (50 mL) was added POCl3 (1.2 g, 7.9 mmol) dropwise and DMF (0.1 mL). The mixture was stirred at 60° C. for 4 hours. After cooling, the mixture was poured into ice-water and extracted with EA three times. The EA layer was washed with brine and dried over Na2SO4. The solvent was removed and the residue was purified by column chromatography on silica gel (DCM/methanol=40/1 v/v %) to afford 8-chloro-3-(1-methyl-4,5,6,7-tetrahydro-1H-indazol-4-yl)imidazo[1,5-a]pyrazine (1.0 g, 70.4%). MS-ESI (m/z): 288 (M+1)+ (Acq Method: 10-80AB_2 min_220 &254.1 cm; Rt: 0.85 min)

후처리

  1. temperatureAfter cooling
  2. extractionextracted with EA three times
  3. washThe EA layer was washed with brine
  4. dry with materialdried over Na2SO4
  5. customThe solvent was removed
  6. customthe residue was purified by column chromatography on silica gel (DCM/methanol=40/1 v/v %)

출처 및 근거

ORD 기록
ord-0627891ac40645dfa111ae4f48a7c8dd
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09446130B2

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