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

HRID 62445ノート

反応式

HRID 62445 の反応式
[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

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

反応条件

温度
60 °C

実験手順

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)

後処理

  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 %)

出典と根拠

ORDレコード
ord-0627891ac40645dfa111ae4f48a7c8dd
出典データセット
uspto-grants-2016_09
特許番号
US09446130B2

反応ノート

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