Dimethylformamide → 8-Chloro-3-(methylsulfanyl)imidazo[1,5-A]pyrazine

HRID 449009ノート

反応式

HRID 449009 の反応式
[CH3:1][S:2][C:3](=O)[NH:4][CH2:5][C:6]1[C:11]([Cl:12])=[N:10][CH:9]=[CH:8][N:7]=1.CN(C=O)C.O=P(Cl)(Cl)Cl>CC#N>[Cl:12][C:11]1[C:6]2[N:7]([C:3]([S:2][CH3:1])=[N:4][CH:5]=2)[CH:8]=[CH:9][N:10]=1

参加物

5

反応物 3

HCID 6228DimethylformamideHCID 24813Phosphorus oxychlorideHCID 59130384(3-chloro-pyrazin-2-ylmethyl)-thiocarbamic acid S-methyl ester

生成物 1

HCID 591303828-Chloro-3-(methylsulfanyl)imidazo[1,5-A]pyrazine収率 63%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

実験手順

To a solution of (3-chloro-pyrazin-2-ylmethyl)-thiocarbamic acid S-methyl ester (3.05 g, 0.0140 mol) in MeCN (70 mL) were added DMF (4.3 mL, 0.056 mol) and POCl3 (5.2 mL, 0.056 mol) at 0° C. under nitrogen. The reaction mixture was slowly warmed to rt and stirred at rt overnight. LC-MS showed the SM was completely consumed. The solvent was evaporated under reduced pressure and the residue was cooled at 0° C. and diluted with EtOAc (250 mL), then quenched with sat. aq. NaHCO3 (100 mL). The mixture was washed brine (50 mL), and dried over anhydrous sodium sulfate. The crude material was purified by silica gel chromatography (Hexane EtOAc=80:20→70:30) to give the title compound as a light-yellow solid, 1.75 g, 63% yield. LC-MS (ES+): 200/202 (3/1) [MH+], and 1H NMR (CDCl3, 400 MHz): δ 2.71 (s, 3H), 7.40 (d, J=5.1 Hz, 1H), 7.74 (dd, J=5.1, 1.0 Hz, 1H), 7.90 (s, 1H).

後処理

  1. customwas completely consumed
  2. customThe solvent was evaporated under reduced pressure
  3. temperaturethe residue was cooled at 0° C.
  4. additiondiluted with EtOAc (250 mL)
  5. customquenched with sat. aq. NaHCO3 (100 mL)
  6. washThe mixture was washed brine (50 mL)
  7. dry with materialdried over anhydrous sodium sulfate
  8. customThe crude material was purified by silica gel chromatography (Hexane EtOAc=80:20→70:30)

出典と根拠

ORDレコード
ord-0c6f8055a2bb4426bb119af9d1a91e00
出典データセット
uspto-grants-2013_07
特許番号
US08481733B2

反応ノート

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